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  • 51.
    Fagerberg, Linn
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hallström, Björn M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Oksvold, Per
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kampf, C.
    Djureinovic, D.
    Odeberg, Jacob
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Habuka, Masato
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Tahmasebpoor, S.
    Danielsson, A.
    Edlund, K.
    Asplund, A.
    Sjöstedt, E.
    Lundberg, E.
    Szigyarto, Cristina Al-Khalili
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Skogs, Marie
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ottosson Takanen, J.
    Berling, H.
    Tegel, Hanna
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Mulder, J.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lindskog, C.
    Danielsson, Frida
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mardinoglu, A.
    Sivertsson, Åsa
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Von Feilitzen, Kalle
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Forsberg, Mattias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Zwahlen, Martin
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Olsson, I.
    Navani, S.
    Huss, Mikael
    Nielsen, Jens
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Pontén, F.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics2014In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 13, no 2, p. 397-406Article in journal (Refereed)
    Abstract [en]

    Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.

  • 52.
    Fagerberg, Linn
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Oksvold, Per
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Skogs, Marie
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Älgenäs, C.
    Lundberg, Emma
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Pontén, F.
    Sivertsson, Åsa
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Odeberg, Jacob
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Klevebring, Daniel
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kampf, C.
    Asplund, A.
    Sjöstedt, E.
    Al-Khalili Szigyarto, C.
    Edqvist, P. -H
    Olsson, I.
    Rydberg, U.
    Hudson, P.
    Ottosson Takanen, J.
    Berling, H.
    Björling, Lisa
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Tegel, Hanna
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Rockberg, J.
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Navani, S.
    Jirström, K.
    Mulder, J.
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Zwahlen, Martin
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hober, Sophia
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Forsberg, Mattias
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Von Feilitzen, Kalle
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Contribution of antibody-based protein profiling to the human chromosome-centric proteome project (C-HPP)2013In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 12, no 6, p. 2439-2448Article in journal (Refereed)
    Abstract [en]

    A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease. Here, we report on the protein evidence for all genes predicted from the genome sequence based on manual annotation from literature (UniProt), antibody-based profiling in cells, tissues and organs and analysis of the transcript profiles using next generation sequencing in human cell lines of different origins. We estimate that there is good evidence for protein existence for 69% (n = 13985) of the human protein-coding genes, while 23% have only evidence on the RNA level and 7% still lack experimental evidence. Analysis of the expression patterns shows few tissue-specific proteins and approximately half of the genes expressed in all the analyzed cells. The status for each gene with regards to protein evidence is visualized in a chromosome-centric manner as part of a new version of the Human Protein Atlas (www.proteinatlas.org).

  • 53.
    Forsström, Bjorn
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Axnäs, Barbara Bislawska
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Stengele, Klaus-Peter
    Buehler, Jochen
    Albert, Thomas J.
    Richmond, Todd A.
    Hu, Francis Jingxin
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hudson, Elton Paul
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Rockberg, Johan
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Proteome-wide Epitope Mapping of Antibodies Using Ultra-dense Peptide Arrays2014In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 13, no 6, p. 1585-1597Article in journal (Refereed)
    Abstract [en]

    Antibodies are of importance for the field of proteomics, both as reagents for imaging cells, tissues, and organs and as capturing agents for affinity enrichment in mass-spectrometry-based techniques. It is important to gain basic insights regarding the binding sites (epitopes) of antibodies and potential cross-reactivity to nontarget proteins. Knowledge about an antibody's linear epitopes is also useful in, for instance, developing assays involving the capture of peptides obtained from trypsin cleavage of samples prior to mass spectrometry analysis. Here, we describe, for the first time, the design and use of peptide arrays covering all human proteins for the analysis of antibody specificity, based on parallel in situ photolithic synthesis of a total of 2.1 million overlapping peptides. This has allowed analysis of on-and off-target binding of both monoclonal and polyclonal antibodies, complemented with precise mapping of epitopes based on full amino acid substitution scans. The analysis suggests that linear epitopes are relatively short, confined to five to seven residues, resulting in apparent off-target binding to peptides corresponding to a large number of unrelated human proteins. However, subsequent analysis using recombinant proteins suggests that these linear epitopes have a strict conformational component, thus giving us new insights regarding how antibodies bind to their antigens.

  • 54.
    Fredolini, Claudia
    et al.
    KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Byström, Sanna
    KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Pin, Elisa
    KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Edfors, Fredrik
    KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Tamburro, Davide
    Iglesias, Maria Jesus
    KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Häggmark, Anna
    KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Immunocapture strategies in translational proteomics2016In: Expert Review of Proteomics, ISSN 1478-9450, E-ISSN 1744-8387, Vol. 13, no 1, p. 83-98Article, review/survey (Refereed)
    Abstract [en]

    Aiming at clinical studies of human diseases, antibody-assisted assays have been applied to biomarker discovery and toward a streamlined translation from patient profiling to assays supporting personalized treatments. In recent years, integrated strategies to couple and combine antibodies with mass spectrometry-based proteomic efforts have emerged, allowing for novel possibilities in basic and clinical research. Described in this review are some of the field's current and emerging immunocapture approaches from an affinity proteomics perspective. Discussed are some of their advantages, pitfalls and opportunities for the next phase in clinical and translational proteomics.

  • 55.
    Fredolini, Claudia
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Byström, Sanna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sanchez-Rivera, Laura
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ioannou, Marina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Tamburro, Davide
    Karolinska Inst, Sci Life Lab, Dept Oncol Pathol, Canc Prote, S-17121 Solna, Sweden..
    Pontén, Fredrik
    Uppsala Univ, Rudbeck Lab, Sci Life Lab, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden..
    Branca, Rui M.
    Karolinska Inst, Sci Life Lab, Dept Oncol Pathol, Canc Prote, S-17121 Solna, Sweden..
    Nilsson, Peter
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lehtio, Janne
    Karolinska Inst, Sci Life Lab, Dept Oncol Pathol, Canc Prote, S-17121 Solna, Sweden..
    Schwenk, Jochen M.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Systematic assessment of antibody selectivity in plasma based on a resource of enrichment profiles2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 8324Article in journal (Refereed)
    Abstract [en]

    There is a strong need for procedures that enable context and application dependent validation of antibodies. Here, we applied a magnetic bead assisted workflow and immunoprecipitation mass spectrometry (IP-MS/MS) to assess antibody selectivity for the detection of proteins in human plasma. A resource was built on 414 IP experiments using 157 antibodies (targeting 120 unique proteins) in assays with heat-treated or untreated EDTA plasma. For each protein we determined their antibody related degrees of enrichment using z-scores and their frequencies of identification across all IP assays. Out of 1,313 unique endogenous proteins, 426 proteins (33%) were detected in >20% of IPs, and these background components were mainly comprised of proteins from the complement system. For 45% (70/157) of the tested antibodies, the expected target proteins were enriched (z-score >= 3). Among these 70 antibodies, 59 (84%) co-enriched other proteins beside the intended target and mainly due to sequence homology or protein abundance. We also detected protein interactions in plasma, and for IGFBP2 confirmed these using several antibodies and sandwich immunoassays. The protein enrichment data with plasma provide a very useful and yet lacking resource for the assessment of antibody selectivity. Our insights will contribute to a more informed use of affinity reagents for plasma proteomics assays.

  • 56. Frostegård, J.
    et al.
    Hellström, Cecilia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Frostegård, A. G.
    Ajeganova, S.
    Autoantibody profiling reveals four protein candidate autoantigens associated with systemic lupus erythematosus2018In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 27, no 10, p. 1670-1678Article in journal (Refereed)
    Abstract [en]

    Objectives In systemic lupus erythematosus (SLE) there are typically many autoantibodies. The disease heterogeneity could be better understood with discovery of phenotype-specific antigens targeted by autoantibodies. We here aimed to identify novel autoantigens potentially related to SLE disease and a major complication, atherosclerosis. Methods Antigen microarrays were used to profile IgG autoantibody reactivity against 77 protein fragments (20-140 amino acids (aa) long, median 89 aa) produced within the Human Protein Atlas project, in serum samples from SLE patients (n=107) and age- and sex-matched population-based controls (n=107). Common carotid intima-media thickness, plaque occurrence and echogenicity were determined by B-mode ultrasound. Results We determined significant differences between patients and controls in IgG reactivity against four proteins. In patients compared to controls, there was an increase of IgG reactivity against zinc finger protein 688 (ZNF688), early B cell factor 2 (EBF2), crystallin, alpha B (CRYAB) and tumor necrosis factor receptor superfamily member 13C (TNFRSF13C). Of these four antigens, only anti-ZNF688 was associated with carotid atherosclerosis (plaque occurrence) and vulnerable plaques in SLE. There was a weak association between anti-EBF2 and SLE disease activity but no significant associations were determined for other measured IgG reactivity. Conclusions In this discovery screening we here demonstrate new candidate autoantigens with differential reactivity (reflecting autoantibody levels) in SLE patients and in controls and in relation to atherosclerosis in SLE.

  • 57.
    Gantelius, Jesper
    et al.
    KTH, School of Biotechnology (BIO), Nano Biotechnology (closed 20130101).
    Bass, Tarek
    KTH, School of Biotechnology (BIO), Molecular Biotechnology (closed 20130101).
    Gundberg, Anna
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101).
    Sundberg, Mårten
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101).
    Sjöberg, Ronald
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101).
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101).
    Andersson-Svahn, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology (closed 20130101).
    A ten-minute high density lateral flow protein microarray assay2011In: 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2011: (MicroTAS 2011), 2011, p. 1176-1178Conference paper (Refereed)
    Abstract [en]

    Protein microarrays are useful tools for highly multiplexed determination of presence or levels of clinically relevant biomarkers in human tissues and biofluids. However, such tools have thus far been restricted to laboratory environments. Here, we present a novel 384-plexed easy to use lateral flow protein microarray device capable of sensitive (<50ng/ml) determination of antigen specific antibodies in less than ten minutes total assay time. Results were developed with gold nanobeads and could be recorded by a cell-phone camera or table top scanner. Excellent accuracy (AUC=99.4%) was achieved in comparison with an established glass microarray assay for 26 antigen-specific antibodies.

  • 58.
    Gantelius, Jesper
    et al.
    KTH, School of Biotechnology (BIO), Nano Biotechnology (closed 20130101).
    Bass, Tarek
    KTH, School of Biotechnology (BIO), Molecular Biotechnology (closed 20130101).
    Sjöberg, Ronald
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Andersson-Svahn, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology (closed 20130101).
    A Lateral Flow Protein Microarray for Rapid and Sensitive Antibody Assays2011In: International Journal of Molecular Sciences, ISSN 1661-6596, Vol. 12, no 11, p. 7748-7759Article in journal (Refereed)
    Abstract [en]

    Protein microarrays are useful tools for highly multiplexed determination of presence or levels of clinically relevant biomarkers in human tissues and biofluids. However, such tools have thus far been restricted to laboratory environments. Here, we present a novel 384-plexed easy to use lateral flow protein microarray device capable of sensitive (<30 ng/mL) determination of antigen-specific antibodies in ten minutes of total assay time. Results were developed with gold nanobeads and could be recorded by a cell-phone camera or table top scanner. Excellent accuracy with an area under curve (AUC of 98% was achieved in comparison with an established glass microarray assay for 26 antigen-specific antibodies. We propose that the presented framework could find use in convenient and cost-efficient quality control of antibody production, as well as in providing a platform for multiplexed affinity-based assays in low-resource or mobile settings.

  • 59. Ge, Changrong P
    et al.
    Tong, Dongmei R
    Liang, Bibo T
    Lonnblom, Erik S
    Schneider, Nadine K
    Hagert, Cecilia U
    Viljanen, Johan V
    Ayoglu, Burcu
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Stawikowska, Roma T
    Nilsson, Peter C.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Fields, Gregg B
    Skogh, Thomas A
    Kastbom, Alf R
    Kihlberg, Jan T
    Burkhardt, Harald T
    Dobritzsch, Doreen C
    Holmdahl, Rikard K
    Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage2017In: JCI INSIGHT, ISSN 2379-3708, Vol. 2, no 13, article id e93688Article in journal (Refereed)
    Abstract [en]

    Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis.

  • 60.
    Ge, Changrong
    et al.
    Karolinska Inst, Stockholm, Sweden..
    Xu, Bingze
    Karolinska Inst, Stockholm, Sweden..
    Liang, Bibo
    Karolinska Inst, Stockholm, Sweden.;Southern Med Univ, Guangzhou, Guangdong, Peoples R China..
    Lonnblom, Erik
    Karolinska Inst, Stockholm, Sweden..
    Lundstrom, Susanna L.
    Karolinska Inst, Stockholm, Sweden..
    Zubarev, Roman A.
    Karolinska Inst, Stockholm, Sweden..
    Ayoglu, Burcu
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Skogh, Thomas
    Linkoping Univ, Linkoping, Sweden..
    Kastbom, Alf
    Linkoping Univ, Linkoping, Sweden..
    Malmstrom, Vivianne
    Karolinska Inst, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Klareskog, Lars
    Karolinska Inst, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Toes, Rene E. M.
    Leiden Univ, Med Ctr, Leiden, Netherlands..
    Rispens, Theo
    Univ Amsterdam, Amsterdam, Netherlands..
    Dobritzsch, Doreen
    Uppsala Univ, Uppsala, Sweden..
    Holmdahl, Rikard
    Karolinska Inst, Stockholm, Sweden.;Southern Med Univ, Guangzhou, Guangdong, Peoples R China..
    Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies2019In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 71, no 2, p. 210-221Article in journal (Refereed)
    Abstract [en]

    Objective Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA. Methods Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients. Results Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients. Conclusion These data show, for the first time, how ACPAs derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone-mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA-specific ACPAs.

  • 61.
    Ge, Changrong
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Xu, Bingze
    Karolinska Inst, Stockholm, Sweden.
    Liang, Bibo
    Karolinska Inst, Stockholm, Sweden;Southern Med Univ, Guangzhou, Guangdong, Peoples R China.
    Lönnblom, Erik
    Karolinska Inst, Stockholm, Sweden.
    Lundström, Susanna L.
    Karolinska Inst, Stockholm, Sweden.
    Zubarev, Roman A.
    Karolinska Inst, Stockholm, Sweden.
    Ayoglu, Burcu
    KTH Royal Inst Technol, Stockholm, Sweden.
    Nilsson, Peter
    KTH Royal Inst Technol, Stockholm, Sweden.
    Skogh, Thomas
    Linkoping Univ, Linkoping, Sweden.
    Kastbom, Alf
    Linkoping Univ, Linkoping, Sweden.
    Malmström, Vivianne
    Karolinska Inst, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Klareskog, Lars
    Karolinska Inst, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Toes, Rene E. M.
    Leiden Univ, Med Ctr, Leiden, Netherlands.
    Rispens, Theo
    Univ Amsterdam, Amsterdam, Netherlands.
    Dobritzsch, Doreen
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Holmdahl, Rikard
    Karolinska Inst, Stockholm, Sweden;Southern Med Univ, Guangzhou, Guangdong, Peoples R China.
    Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies2019In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 71, no 2, p. 210-221Article in journal (Refereed)
    Abstract [en]

    Objective: Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA.

    Methods: Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients.

    Results: Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients.

    Conclusion: These data show, for the first time, how ACPAs derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone-mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA-specific ACPAs.

  • 62. Grans, H.
    et al.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics.
    Evengard, B.
    Gene expression profiling in the chronic fatigue syndrome2005In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 258, no 4, p. 388-390Article in journal (Refereed)
  • 63.
    Gry, Marcus
    et al.
    KTH, School of Biotechnology (BIO), Proteomics.
    Rimini, Rebecca
    KTH, School of Biotechnology (BIO), Proteomics.
    Strömberg, Sara
    Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital.
    Asplund, Anna
    Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital.
    Pontén, Fredrik
    Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics.
    Correlations between RNA and protein expression profiles in 23 human cell lines2009In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 10Article in journal (Refereed)
    Abstract [en]

    Background: The Central Dogma of biology holds, in famously simplified terms, that DNA makes RNA makes proteins, but there is considerable uncertainty regarding the general, genome-wide correlation between levels of RNA and corresponding proteins. Therefore, to assess degrees of this correlation we compared the RNA profiles (determined using both cDNA- and oligo-based microarrays) and protein profiles (determined immunohistochemically in tissue microarrays) of 1066 gene products in 23 human cell lines. Results: A high mean correlation coefficient (0.52) was obtained from the pairwise comparison of RNA levels determined by the two platforms. Significant correlations, with correlation coefficients exceeding 0.445, between protein and RNA levels were also obtained for a third of the specific gene products. However, the correlation coefficients between levels of RNA and protein products of specific genes varied widely, and the mean correlations between the protein and corresponding RNA levels determined using the cDNA- and oligo-based microarrays were 0.25 and 0.20, respectively. Conclusion: Significant correlations were found in one third of the examined RNA species and corresponding proteins. These results suggest that RNA profiling might provide indirect support to antibodies’ specificity, since whenever a evident correlation between the RNA and protein profiles exists, this can sustain that the antibodies used in the immunoassay recognized their cognate antigens.

  • 64.
    Gräns, Hanna
    et al.
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101).
    Evengård, Birgitta
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101).
    Transcriptome Analysis of Peripheral Blood Mononuclear Cells from Patients with Chronic Fatigue Syndrome2008In: Journal of Chronic Fatigue Syndrome, ISSN 1057-3321, E-ISSN 1547-0660, Vol. 14, no 3, p. 7-25Article in journal (Refereed)
    Abstract [en]

    Objective: Chronic fatigue syndrome (CFS) is an illness defined by unexplained disabling fatigue lasting longer than six months, together with at least four out of eight specified symptoms. The etiology and pathophysiology of CFS are to a large degree unknown. Since much remains unclear about CFS we wanted to investigate transcript expression levels in peripheral blood mononuclear cells to identify genes that are involved in CFS. Method: Transcript expression profiles for 20 CFS patients were compared with 14 healthy controls using microarray technology. Results were verified with real-time PCR. Results: We have identified significantly differentially expressed genes comparing a female CFS patient subgroup with gradual illness onset and no previously documented infection with female healthy controls. We have also created a list of genes with indicated, but not verified, expression differences from comparisons between other subgroups and healthy controls. These genes are candidates for further study of potential involvement in CFS. Conclusion: Our results stress the necessity of subgrouping the heterogeneous CFS patient cohort. The mRNA expression differences identified here may be causal factors for the illness or symptoms observed in these patients, or a result of altered functions of other cellular components involved in the illness. The role of these genes in the CFS pathology needs further investigation.

  • 65.
    Hambardzumyan, K.
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Hamsten, C.
    Karolinska Inst, Dept Med, Unit Immunol & Allergy, Stockholm, Sweden..
    Idborg, H.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Lourido, Lucia Maria
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Saevarsdottir, S.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    van Vollenhoven, R. F.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Amsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands..
    Jakobsson, P. -J
    EVALUATION OF SERUM PROTEIN LEVELS AT BASELINE AS PREDICTORS OF RESPONSE TO METHOTREXATE IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: RESULTS FROM SWEFOT TRIAL POPULATION2018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, p. 569-570Article in journal (Other academic)
  • 66.
    Hambardzumyan, K.
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Hamsten, C.
    Karolinska Univ Hosp Solna, Stockholm, Sweden.;Karolinska Inst, Dept Med, Unit Immunol & Allergy, Stockholm, Sweden..
    Idborg, H.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Lourido, Lucia
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Saevarsdottir, S.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    van Vollenhoven, R.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Jakobsson, P.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Evaluation of serum protein levels at baseline as predictors of response to methotrexate in patients with early rheumatoid arthritis: results from the SWEFOT trial population2018In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, p. 31-31Article in journal (Other academic)
  • 67. Hamsten, C.
    et al.
    Häggmark, Anna
    KTH.
    Grundstrom, J.
    Mikus, Maria
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Lindskog, C.
    Konradsen, J. R.
    Eklund, A.
    Pershagen, G.
    Wickman, M.
    Grunewald, J.
    Melen, E.
    Hedlin, G.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    van Hage, M.
    Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma2016In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 71, no 9, p. 1357-1361Article in journal (Refereed)
    Abstract [en]

    Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma.

  • 68. Hamsten, C.
    et al.
    Skattum, L.
    Truedsson, L.
    von Döbeln, U.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hammarström, L.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Neiman, Maja
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Heat differentiated complement factor profiling2015In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 126, p. 155-162Article in journal (Refereed)
    Abstract [en]

    Complement components and their cascade of reactions are important defense mechanisms within both innate and adaptive immunity. Many complement deficient patients still remain undiagnosed because of a lack of high throughput screening tools. Aiming towards neonatal proteome screening for immunodeficiencies, we used a multiplex profiling approach with antibody bead arrays to measure 9 complement proteins in serum and dried blood spots. Several complement components have been described as heat sensitive, thus their heat-dependent detectability was investigated. Using sera from 16 patients with complement deficiencies and 23 controls, we confirmed that the proteins C1q, C2, C3, C6, C9 and factor H were positively affected by heating, thus the identification of deficient patients was improved when preheating samples. Measurements of C7, C8 and factor I were negatively affected by heating and non-heated samples should be used in analysis of these components. In addition, a proof of concept study demonstrated the feasibility of labeling eluates from dried blood spots to perform a subsequent correct classification of C2-deficiencies. Our study demonstrates the potential of using multiplexed single binder assays for screening of complement components that open possibilities to expand such analysis to other forms of deficiencies.

  • 69. Hamsten, Carl
    et al.
    Wiklundh, Emil
    Gronlund, Hans
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlen, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Eklund, Anders
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Grunewald, Johan
    Haggmark-Manberg, Anna
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Elevated levels of FN1 and CCL2 in bronchoalveolar lavage fluid from sarcoidosis patients2016In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 17, article id 69Article in journal (Refereed)
    Abstract [en]

    Background: Sarcoidosis is a granulomatous systemic inflammatory disease in which more than 90 % of all patients develop pulmonary manifestations. Several gene associations have previously been described, but established and clinically useful biomarkers are still absent. This study aimed to find proteins in bronchoalveolar lavage (BAL) fluid that can be associated with the disease. Methods: We developed and performed profiling of 94 selected proteins in BAL fluid and serum samples obtained from newly diagnosed and non-treated patients with sarcoidosis. Using multiplexed immunoassays, a total of 317 BAL and 217 serum samples were analyzed, including asthmatic patients and healthy individuals as controls. Results: Our analyses revealed increased levels of eight proteins in sarcoidosis patients compared to controls. Out of these, fibronectin (FN1) and C-C motif chemokine 2 (CCL2) revealed the strongest associations. In addition, cadherin 5 (CDH5) was found to correlate positively with lymphocyte cell numbers in BAL fluid. Conclusions: Applying a high throughput proteomics screening technique, we found proteins of potential clinical relevance in the context of sarcoidosis.

  • 70. Hedberg, Jesper
    et al.
    Neiman, Maja
    KTH, School of Biotechnology (BIO), Proteomics.
    Donnes, Pierre
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics.
    Molecular profiling of human kidney injury using antibody suspension bead arrays2009In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 189, p. S94-S94Article in journal (Other academic)
  • 71.
    Hellström, Cecilia
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Dodig-Crnković, Tea
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sjöberg, Ronald
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    High-density serum/plasma reverse phase protein arrays2017In: Serum/Plasma Proteomics, Humana Press, 2017, p. 229-238Chapter in book (Refereed)
    Abstract [en]

    In-depth exploration and characterization of human serum and plasma proteomes is an attractive strategy for the identification of potential prognostic or diagnostic biomarkers. The possibility of analyzing larger numbers of samples in a high-throughput fashion has markedly increased with affinity-based microarrays, thus providing higher statistical power to these biomarker studies. Here, we describe a protocol for high-density serum and plasma reverse phase protein arrays (RPPAs). We demonstrate how a biobank of 12,392 samples was immobilized and analyzed on a single microarray slide, allowing high-quality profiling of abundant target proteins across all samples in one assay.

  • 72.
    Henjes, Frauke
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lourido, Lucia
    Ruiz-Romero, Cristina
    Fernandez-Tajes, Juan
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Gonzalez-Gonzalez, Maria
    Banco, Francisco J.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Fuentes, Manuel
    Analysis of Autoantibody Profiles in Osteoarthritis Using Comprehensive Protein Array Concepts2014In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 13, no 11, p. 5218-5229Article in journal (Refereed)
    Abstract [en]

    Osteoarthritis (OA) is the most common rheumatic disease and one of the most disabling pathologies worldwide. To date, the diagnostic methods of OA are very limited, and there are no available medications capable of halting its characteristic cartilage degeneration. Therefore, there is a significant interest in new biomarkers useful for the early diagnosis, prognosis, and therapeutic monitoring. In the recent years, protein microarrays have emerged as a powerful proteomic tool to search for new biomarkers. In this study, we have used two concepts for generating protein arrays, antigen microarrays, and NAPPA (nucleic acid programmable protein arrays), to characterize differential autoantibody profiles in a set of 62 samples from OA, rheumatoid arthritis (RA), and healthy controls. An untargeted screen was performed on 3840 protein fragments spotted on planar antigen arrays, and 373 antigens were selected for validation on bead-based arrays. In the NAPPA approach, a targeted screening was performed on 80 preselected proteins. The autoantibody targeting CHST14 was validated by ELISA in the same set of patients. Altogether, nine and seven disease related autoantibody target candidates were identified, and this work demonstrates a combination of these two array concepts for biomarker discovery and their usefulness for characterizing disease-specific autoantibody profiles.

  • 73. Henriquez-Hernandez, L. A.
    et al.
    Flores-Morales, A.
    Santana-Farre, R.
    Axelson, M.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics.
    Norstedt, G.
    Fernandez-Perez, L.
    Role of pituitary hormones on 17 alpha-ethinylestradiol-induced cholestasis in rat2007In: Journal of Pharmacology and Experimental Therapeutics, ISSN 0022-3565, E-ISSN 1521-0103, Vol. 320, no 2, p. 695-705Article in journal (Refereed)
    Abstract [en]

    Estrogens cause intrahepatic cholestasis in susceptible women during pregnancy, after administration of oral contraceptives, or during postmenopausal hormone replacement therapy. 17 alpha-Ethinylestradiol ( EE) is a synthetic estrogen widely used to cause experimental cholestasis in rodents with the aim of examining molecular mechanisms involved in this disease. EE actions on the liver are thought to be mediated by estrogen receptor alpha ( ER alpha) and pituitary hormones. We tested this hypothesis by analyzing metabolic changes induced by EE in livers from hypophysectomized ( HYPOX) and hypothyroid rats. Microarray studies revealed that the number of genes regulated by EE was increased almost 4-fold in HYPOX rat livers compared with intact males. Little overlap was apparent between the effects of EE in intact and HYPOX rats, demonstrating that pituitary hormones play a critical role in the hepatic effects of EE. Consistently, hypophysectomy protects the liver against induction by EE of serum bilirubin and alkaline phosphatase, two markers of cholestasis and hepatotoxicity and modulates the effects of EE on several genes involved in bile acid homeostasis ( e. g., FXR, SHP, BSEP, and Cyp8b1). Finally, we demonstrate a novel mechanism of action of EE through binding and negative regulation of glucocorticoid receptor-mediated transcription. In summary, pituitary- and ER alpha- independent mechanisms contribute to development of EE-induced changes in liver transcriptome. Such mechanisms may be relevant when this model of EE-induced cholestasis is evaluated. The observation that the pharmacological effects of estrogen in liver differ in the absence or presence of the pituitary could be clinically relevant, because different drugs that block actions of pituitary hormones are now available.

  • 74. Hertzberg, M.
    et al.
    Aspeborg, H.
    Schrader, J.
    Andersson, A.
    Erlandsson, R.
    Blomqvist, K.
    Bhalerao, R.
    Uhlén, Mathias
    KTH, Superseded Departments, Biotechnology.
    Teeri, Tuula T.
    KTH, Superseded Departments, Biotechnology.
    Lundeberg, Joakim
    KTH, Superseded Departments, Biotechnology.
    Sundberg, B.
    Nilsson, Peter
    KTH, Superseded Departments, Biotechnology.
    Sandberg, G.
    A transcriptional roadmap to wood formation2001In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 98, no 25, p. 14732-14737Article in journal (Refereed)
    Abstract [en]

    The large vascular meristem of poplar trees with its highly organized secondary xylem enables the boundaries between different developmental zones to be easily distinguished. This property of wood-forming tissues allowed us to determine a unique tissue-specific transcript profile for a well defined developmental gradient. RNA was prepared from different developmental stages of xylogenesis for DNA microarray analysis by using a hybrid aspen unigene set consisting of 2,995 expressed sequence tags. The analysis revealed that the genes encoding lignin and cellulose biosynthetic enzymes, as well as a number of transcription factors and other potential regulators of xylogenesis, are under strict developmental stage-specific transcriptional regulation.

  • 75. Hertzberg, Magnus
    et al.
    Aspeborg, Henrik
    KTH, Superseded Departments, Biotechnology.
    Sievertzon, Maria
    KTH, Superseded Departments, Biotechnology.
    Nilsson, Peter
    KTH, Superseded Departments, Biotechnology.
    Sandberg, G.
    Lundeberg, Joakim
    KTH, Superseded Departments, Biotechnology.
    cDNA microarray analysis of small tissue samples using a cDNA tag target amplification protocol2001In: The Plant Journal, ISSN 0960-7412, E-ISSN 1365-313X, Vol. 25, no 5, p. 585-591Article in journal (Refereed)
    Abstract [en]

    Microarray technology is becoming an important comprehensive tool to study gene expression in plants. However, the use of this technology is limited by the large amount of sample tissue needed for microarray analysis. Generally, 50-200 mug of total RNA and 1-2 mug of mRNA is required for each hybridisation, which is equivalent to 50-100 mg of plant tissue. This requirement for large amounts of starting material severely constrains the use of microarrays for transcript profiling in specific tissues and cell types during plant development. Here we report on a robust and reliable target amplification method that enables transcript profiling from sub-mg amounts of plant tissue. Using 0.1 mug of total RNA we show that twofold expression differences are possible to distinguish with 99% confidence. We also demonstrate the application of this method in an analysis of secondary phloem development in hybrid aspen using defined tissue sections, corresponding to 2-4 cell layers with a fresh weight of similar to 0.5 mg.

  • 76.
    Hjelm, Barbara
    et al.
    KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Forsström, Björn
    KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Igel, Ulrika
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Johannesson, Henrik
    Stadler, Charlotte
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundberg, Emma
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ponten, Fredrik
    Sjoberg, Anna
    Rockberg, Johan
    KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Johansson, Christine
    Uhlen, Mathias
    KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Generation of monospecific antibodies based on affinity capture of polyclonal antibodies2011In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 20, no 11, p. 1824-1835Article in journal (Refereed)
    Abstract [en]

    A method is described to generate and validate antibodies based on mapping the linear epitopes of a polyclonal antibody followed by sequential epitope-specific capture using synthetic peptides. Polyclonal antibodies directed towards four proteins RBM3, SATB2, ANLN, and CNDP1, potentially involved in human cancers, were selected and antibodies to several non-overlapping epitopes were generated and subsequently validated by Western blot, immunohistochemistry, and immunofluorescence. For all four proteins, a dramatic difference in functionality could be observed for these monospecific antibodies directed to the different epitopes. In each case, at least one antibody was obtained with full functionality across all applications, while other epitope-specific fractions showed no or little functionality. These results present a path forward to use the mapped binding sites of polyclonal antibodies to generate epitope-specific antibodies, providing an attractive approach for large-scale efforts to characterize the human proteome by antibodies.

  • 77.
    Hong, Mun-Gwan
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Lee, Woojoo
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Pawitan, Yudi
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Multidimensional Normalization to Minimize Plate Effects of Suspension Bead Array Data2016In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 15, no 10, p. 3473-3480Article in journal (Refereed)
    Abstract [en]

    Enhanced by the growing number of biobanks, biomarker studies can now be performed with reasonable statistical power by using large sets of samples. Antibody-based proteomics by means of suspension bead arrays offers one attractive approach to analyze serum, plasma, or CSF samples for such studies in microtiter plates. To expand measurements beyond single batches, with either 96 or 384 samples per plate, suitable normalization methods are required to minimize the variation between plates. Here we propose two normalization approaches utilizing MA coordinates. The multidimensional MA (multi-MA) and MA-loess both consider all samples of a microtiter plate per suspension bead array assay and thus do not require any external reference samples. We demonstrate the performance of the two MA normalization methods with data obtained from the analysis of 384 samples including both serum and plasma. Samples were randomized across 96-well sample plates, processed, and analyzed in assay plates, respectively. Using principal component analysis (PCA), we could show that plate-wise clusters found in the first two components were eliminated by multi-MA normalization as compared with other normalization methods. Furthermore, we studied the correlation profiles between random pairs of antibodies and found that both MA normalization methods substantially reduced the inflated correlation introduced by plate effects. Normalization approaches using multi-MA and MA-loess minimized batch effects arising from the analysis of several assay plates with antibody suspension bead arrays. In a simulated biomarker study, multi-MA restored associations lost due to plate effects. Our normalization approaches, which are available as R package MDimNornin, could also be useful in studies using other types of high-throughput assay data.

  • 78.
    Häggmark, Anna
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Bradley, Frideborg
    Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Med Solna,Unit Infect Dis, Stockholm, Sweden..
    Qundos, Ulrika
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Guthrie, Brandon L.
    Univ Washington, Dept Global Hlth, Washington, DC USA.;Univ Washington, Dept Epidemiol Hlth, Washington, DC USA..
    Birse, Kenzie
    Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.;Publ Hlth Agcy Canada, JC Wilt Infect Dis Ctr, Natl HIV & Retrovirol Labs, Winnipeg, MB, Canada..
    Noel-Romas, Laura
    Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.;Publ Hlth Agcy Canada, JC Wilt Infect Dis Ctr, Natl HIV & Retrovirol Labs, Winnipeg, MB, Canada..
    Lindskog, Cecilia
    Uppsala Univ, Dept Immunol Genet & Pathol, SciLifeLab, Uppsala, Sweden..
    Bosire, Rose
    Kenya Govt Med Res Ctr, Nairobi, Kenya..
    Kiarie, James
    Univ Nairobi, Dept Obstet & Gynecol, Nairobi, Kenya..
    Farquhar, Carey
    Univ Washington, Dept Med Global Hlth & Epidemiol, Seattle, WA 98195 USA..
    Burgener, Adam D.
    Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Med Solna,Unit Infect Dis, Stockholm, Sweden.;Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.;Publ Hlth Agcy Canada, JC Wilt Infect Dis Ctr, Natl HIV & Retrovirol Labs, Winnipeg, MB, Canada..
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Broliden, Kristina
    Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Med Solna,Unit Infect Dis, Stockholm, Sweden..
    A High-throughput Bead-based Affinity Assay Enables Analysis of Genital Protein Signatures in Women At Risk of HIV Infection2019In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 18, no 3, p. 461-476Article in journal (Refereed)
    Abstract [en]

    Women at high risk of HIV infection, including sex workers and those with active genital inflammation, have molecular signatures of immune activation and epithelial barrier remodeling in samples of their genital mucosa. These alterations in the local immunological milieu are likely to impact HIV susceptibility. We here analyze host genital protein signatures in HIV uninfected women, with high frequency of condom use, living in HIV-serodiscordant relationships. Cervicovaginal secretions from women living in HIV-serodiscordant relationships (n = 62) were collected at three time points over 12 months. Women living in HIV-negative seroconcordant relationships (controls, n = 25) were sampled at one time point. All study subjects were examined for demographic parameters associated with susceptibility to HIV infection. The cervicovaginal samples were analyzed using a high-throughput bead-based affinity assay. Proteins involved in epithelial barrier function and inflammation were increased in HIV-serodiscordant women. By combining several methods of analysis, a total of five proteins (CAPG, KLK10, SPRR3, elafin/PI3, CSTB) were consistently associated with this study group. Proteins analyzed using the affinity set-up were further validated by label-free tandem mass spectrometry in a partially overlapping cohort with concordant results. Women living in HIV-serodiscordant relationships thus had elevated levels of proteins involved in epithelial barrier function and inflammation despite low prevalence of sexually transmitted infections and a high frequency of safe sex practices. The identified proteins are important markers to follow during assessment of mucosal HIV susceptibility factors and a high-throughput bead-based affinity set-up could be a suitable method for such evaluation.

  • 79.
    Häggmark, Anna
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Byström, Sanna
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ayoglu, Burcu
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Qundos, Ulrika
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Khademi, M.
    Olsson, T.
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Antibody-based profiling of cerebrospinal fluid within multiple sclerosis2013In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 13, no 15, p. 2256-2267Article in journal (Refereed)
    Abstract [en]

    Antibody suspension bead arrays have proven to enable multiplexed and high-throughput protein profiling in unfractionated plasma and serum samples through a direct labeling approach. We here describe the development and application of an assay for protein profiling of cerebrospinal fluid (CSF). While setting up the assay, systematic intensity differences between sample groups were observed that reflected inherent sample specific total protein amounts. Supplementing the labeling reaction with BSA and IgG diminished these differences without impairing the apparent sensitivity of the assay. We also assessed the effects of heat treatment on the analysis of CSF proteins and applied the assay to profile 43 selected proteins by 101 antibodies in 339 CSF samples from a multiple sclerosis (MS) cohort. Two proteins, GAP43 and SERPINA3 were found to have a discriminating potential with altered intensity levels between sample groups. GAP43 was detected at significantly lower levels in secondary progressive MS compared to early stages of MS and the control group of other neurological diseases. SERPINA3 instead was detected at higher levels in all MS patients compared to controls. The developed assay procedure now offers new possibilities for broad-scale protein profiling of CSF within neurological disorders.

  • 80.
    Häggmark, Anna
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hamsten, Carl
    Wiklundh, Emil
    Lindskog, Cecilia
    Mattsson, Cecilia
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Andersson, Eni
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundberg, Ingrid E.
    Gronlund, Hans
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Eklund, Anders
    Grunewald, Johan
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Proteomic Profiling Reveals Autoimmune Targets in Sarcoidosis2015In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191, no 5, p. 574-583Article in journal (Refereed)
    Abstract [en]

    Rationale: There is a need to further characterize the antibody repertoire in relation to sarcoidosis and potentially related autoantigens. Objectives: We investigated bronchoalveolar lavage (BAL) and serum samples from patients with sarcoidosis and healthy and diseased control subjects to discover sarcoidosis-associated autoantigens. Methods: Antigen microarrays built on 3,072 protein fragments were used to screen for IgG reactivity in 73 BAL samples from subjects with sarcoidosis, subjects with asthma, and healthy subjects. A set of 131 targets were selected for subsequent verification on suspension bead arrays using 272 additional BAL samples and 141 paired sera. Reactivity to four antigens was furthermore analyzed in 22 unprocessed BAL samples from patients with fibrosis and 269 plasma samples from patients diagnosed with myositis. Measurements and Main Results: Reactivity toward zinc finger protein 688 and mitochondrial ribosomal protein L43 were discovered with higher frequencies in patients with sarcoidosis, for mitochondrial ribosomal protein L43 especially in patients with non-Lofgren syndrome. Increased reactivity toward nuclear receptor coactivator 2 was also observed in patients with non-Lofgren syndrome as compared with patients with Lofgren syndrome. The antigen representing adenosine diphosphate-ribosylation factor GTPase activating protein 1 revealed high reactivity frequency in all sample groups but with significantly higher level of IgG reactivities in patients with sarcoidosis. Conclusions: Autoantigen reactivity was present in most BAL and serum samples analyzed, and the results revealed high interindividual heterogeneity, with most of the reactivities observed in single individuals only. Four proteins are here proposed as sarcoidosis-associated autoimmune targets and of interest for further validation in independent cohorts.

  • 81.
    Häggmark, Anna
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mikus, Maria
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mohsenchian, Atefeh
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Forsström, Björn
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Gajewska, Beata
    Baranczyk-Kuzma, Anna
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kuzma-Kozakiewicz, Magdalena
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Plasma profiling revelas three proteins associated to amyotrophic lateral sclerosis2014In: Annals of Clinical and Translational Neurology, ISSN 2328-9503, Vol. 1, no 8, p. 544-553Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is the most common adult motor neuron disease leading to muscular paralysis and death within 3-5 years from onset. Currently, there are no reliable and sensitive markers able to substantially shorten the diagnosis delay. The objective of the study was to analyze a large number of proteins in plasma from patients with various clinical phenotypes of ALS in search for novel proteins or protein profiles that could serve as potential indicators of disease.

    METHODS: Affinity proteomics in the form of antibody suspension bead arrays were applied to profile plasma samples from 367 ALS patients and 101 controls. The plasma protein content was directly labeled and protein profiles obtained using 352 antibodies from the Human Protein Atlas targeting 278 proteins. A focused bead array was then built to further profile eight selected protein targets in all available samples.

    RESULTS: Disease-associated significant differences were observed and replicated for profiles from antibodies targeting the proteins: neurofilament medium polypeptide (NEFM), solute carrier family 25 (SLC25A20), and regulator of G-protein signaling 18 (RGS18).

    INTERPRETATION: Upon further validation in several independent cohorts with inclusion of a broad range of other neurological disorders as controls, the alterations of these three protein profiles in plasma could potentially provide new molecular markers of disease that contribute to the quest of understanding ALS pathology.

  • 82.
    Häggmark, Anna
    et al.
    KTH, School of Biotechnology (BIO), Proteomics.
    Neiman, Maja
    KTH, School of Biotechnology (BIO), Proteomics.
    Drobin, Kimi
    KTH, School of Biotechnology (BIO), Proteomics.
    Zwahlen, Martin
    KTH, School of Biotechnology (BIO), Proteomics.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics.
    Schwenk, Jochen M
    KTH, School of Biotechnology (BIO), Proteomics.
    Classification of protein profiles from antibody microarrays using heat and detergent treatment.2011In: New Biotechnology, ISSN 1871-6784, E-ISSN 1876-4347, Vol. 29, no 5, p. 564-570Article in journal (Refereed)
    Abstract [en]

    Antibody microarrays offer new opportunities for exploring the proteome and to identify biomarker candidates in human serum and plasma. Here, we have investigated the effect of heat and detergents on an antibody-based suspension bead array (SBA) assay using polyclonal antibodies and biotinylated plasma samples. With protein profiles from more than 2300 antibodies generated in 384-plex antibody SBAs, three major classes of heat and detergent susceptibility could be described. The results show that washing of the beads with SDS (rather than Tween) after target binding lowered intensity levels of basically all profiles and that about 50% of the profiles appeared to be lowered to a similar extent by heating of the sample. About 33% of the profiles appeared to be insensitive to heat treatment while another 17% showed a positive influence of heat to yield elevated profiles. The results suggest that the classification of antibodies is driven by the molecular properties of the antibody-antigen interaction and can generally not be predicted based on protein class or Western blot data. The experimental scheme presented here can be used to systematically categorize antibodies and thereby combine antibodies with similar properties into targeted arrays for analysis of plasma and serum.

  • 83.
    Häggmark, Anna
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Neuroproteomic profiling of human body fluids2016In: PROTEOMICS - Clinical Applications, ISSN 1862-8346, E-ISSN 1862-8354, Vol. 10, no 4, p. 485-502Article, review/survey (Refereed)
    Abstract [en]

    Analysis of protein expression and abundance provides a possibility to extend the current knowledge on disease-associated processes and pathways. The human brain is a complex organ and dysfunction or damage can give rise to a variety of neurological diseases. Although many proteins potentially reflecting disease progress are originating from brain, the scarce availability of human tissue material has lead to utilization of body fluids such as cerebrospinal fluid and blood in disease-related research. Within the most common neurological disorders, much effort has been spent on studying the role of a few hallmark proteins in disease pathogenesis but despite extensive investigation, the signatures they provide seem insufficient to fully understand and predict disease progress. In order to expand the view the field of neuroproteomics has lately emerged alongside developing technologies, such as affinity proteomics and mass spectrometry, for multiplexed and high-throughput protein profiling. Here, we provide an overview of how such technologies have been applied to study neurological disease and we also discuss some important considerations concerning discovery of disease-associated profiles.

  • 84.
    Häggmark, Anna
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Zandian, Arash
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Forsström, Björn
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Autoantibody targets in vaccine-associated narcolepsyManuscript (preprint) (Other academic)
  • 85.
    Häggmark-Månberg, Anna
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Neuroproteomic profiling of cerebrospinal fluid (CSF) by multiplexed affinity arrays2017In: Neuroproteomics: Methods and Protocols, Humana Press, 2017, p. 247-254Chapter in book (Refereed)
    Abstract [en]

    Protein profiling through affinity proteomic approaches represents a powerful strategy for the analysis of human body fluids. Cerebrospinal fluid (CSF), being the fluid proximal to the central nervous system, is commonly analyzed in the context of neurological diseases, and can offer novel insights into the physiological state of the brain. Ultimately, and by analyzing the presence of brain-derived proteins in larger sets of samples that represent different phenotypes, profiling of CSF may serve as an important source to discover and verify disease-associated markers. Here, we describe a multiplexed and flexible protein profiling approach using antibody-based assays on suspension bead arrays. Through streamlined sample processing, protein biotinylation, and single-binder assay readout, this method enables high-throughput neuroproteomic analysis of up to 384 proteins in 384 samples.

  • 86.
    Häggmark-Månberg, Anna
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Zandian, Arash
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Forsström, Björn
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Khademi, Mohsen
    Bomfim, Izaura Lima
    Hellström, Cecilia
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Arnheim-Dahlström, Lisen
    Hallböök, Tove
    Darin, Niklas
    Lundberg, Ingrid E.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Partinen, Markku
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Olsson, Tomas
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Autoantibody targets in vaccine-associated narcolepsy2016In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 49, no 6, p. 421-433Article in journal (Refereed)
    Abstract [en]

    Narcolepsy is a chronic sleep disorder with a yet unknown cause, but the specific loss of hypocretin-producing neurons together with a strong human leukocyte antigen (HLA) association has led to the hypothesis that autoimmune mechanisms might be involved. Here, we describe an extensive effort to profile autoimmunity repertoires in serum with the aim to find disease-related autoantigens. Initially, 57 serum samples from vaccine-associated and sporadic narcolepsy patients and controls were screened for IgG reactivity towards 10 846 fragments of human proteins using planar microarrays. The discovered differential reactivities were verified on suspension bead arrays in the same sample collection followed by further investigation of 14 antigens in 176 independent samples, including 57 narcolepsy patients. Among these 14 antigens, methyltransferase-like 22 (METTL22) and 5'-nucleotidase cytosolic IA (NT5C1A) were recognized at a higher frequency in narcolepsy patients of both sample sets. Upon sequence analysis of the 14 proteins, polymerase family, member 3 (PARP3), acyl-CoA-binding domain containing 7 (ARID4B), glutaminase 2 (GLS2) and cyclin-dependent kinase-like 1 (CDKL1) were found to contain amino acid sequences with homology to proteins found in the H1N1 vaccine. These findings could become useful elements of further clinical assays that aim towards a better phenotypic understanding of narcolepsy and its triggers.

  • 87.
    Idborg, H.
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Zandian, Arash
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Gustafsson, J. T.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Gunnarsson, I.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Svenungsson, E.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Jakobsson, P. J.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    CHARACTERISATION OF SYSTEMIC LUPUS ERYTHEMATOSUS SUBGROUPS WITH FEATURES OF ANTIPHOSPHOLIPID OR SJOGRENS'S SYNDROME UTILISING AFFINITY PROTEOMICS2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, p. A53-A53Article in journal (Other academic)
  • 88.
    Idborg, H.
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Zandian, Arash
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Gustafsson, J. T.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gunnarsson, I.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Svenungsson, E.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Jakobsson, P. -J
    CHARACTERIZATION OF SYSTEMIC LUPUS ERYTHEMATOSUS SUBGROUPS WITH FEATURES OF ANTIPHOSPHOLIPID OR SJOGRENS'S SYNDROME UTILIZING AFFINITY PROTEOMICS2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, p. 116-116Article in journal (Other academic)
  • 89. Idborg, H.
    et al.
    Zandian, Arash
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Gustafsson, J. T.
    Gunnarsson, I.
    Svenungsson, E.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Jakobsson, P-J
    Characterization of systemic lupus erythematosus subgroups with features of antiphospholipid syndrome or Sjogren's syndrome using affinity proteomics2016In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 45, p. 4-4Article in journal (Other academic)
  • 90. Idborg, Helena
    et al.
    Zandian, Arash
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hellstrom, Cecilia
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mattsson, Cecilia
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Fredolini, Claudia
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Ayoglu, Burcu
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Neiman, Maja
    Gunnarsson, Iva
    Svenungsson, Elisabet
    Jakobsson, Per-Johan
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    PROTEIN PROFILING IN PLASMA REVEALS MOLECULAR SUBGROUPS IN SYSTEMIC LUPUS ERYTHEMATOSUS2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. A52-A52Article in journal (Refereed)
  • 91.
    Idborg, Helena
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
    Zandian, Arash
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Ossipova, Elena
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
    Wigren, Edvard
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
    Preger, Charlotta
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
    Mobarrez, Fariborz
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden.;Uppsala Univ, Akad Hosp, Dept Med Sci, Uppsala, Sweden..
    Checa, Antonio
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, Stockholm, Sweden..
    Sohrabian, Azita
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Pucholt, Pascal
    Uppsala Univ, Dept Med Sci, Rheumatol, Uppsala, Sweden..
    Sandling, Johanna K.
    Uppsala Univ, Dept Med Sci, Rheumatol, Uppsala, Sweden..
    Fernandes-Cerqueira, Catia
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
    Ronnelid, Johan
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Oke, Vilija
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
    Grosso, Giorgia
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
    Kvarnstrom, Marika
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
    Larsson, Anders
    Uppsala Univ, Dept Med Sci, Clin Chem, Uppsala, Sweden..
    Wheelock, Craig E.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, Stockholm, Sweden..
    Syvanen, Ann-Christine
    Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, Uppsala, Sweden..
    Ronnblom, Lars
    Uppsala Univ, Dept Med Sci, Rheumatol, Uppsala, Sweden..
    Kultima, Kim
    Uppsala Univ, Dept Med Sci, Clin Chem, Uppsala, Sweden..
    Persson, Helena
    KTH Royal Inst Technol, Sci Life Lab, Drug Discovery & Dev, Stockholm, Sweden.;KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Stockholm, Sweden..
    Graslund, Susanne
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
    Jakobsson, Per-Johan
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Div Rheumatol, Stockholm, Sweden..
    Circulating Levels of Interferon Regulatory Factor-5 Associates With Subgroups of Systemic Lupus Erythematosus Patients2019In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 1029Article in journal (Refereed)
    Abstract [en]

    Systemic Lupus Erythematosus (SLE) is a heterogeneous autoimmune disease, which currently lacks specific diagnostic biomarkers. The diversity within the patients obstructs clinical trials but may also reflect differences in underlying pathogenesis. Our objective was to obtain protein profiles to identify potential general biomarkers of SLE and to determine molecular subgroups within SLE for patient stratification. Plasma samples from a cross-sectional study of well-characterized SLE patients (n = 379) and matched population controls (n = 316) were analyzed by antibody suspension bead array targeting 281 proteins. To investigate the differences between SLE and controls, Mann-Whitney U-test with Bonferroni correction, generalized linear modeling and receiver operating characteristics (ROC) analysis were performed. K-means clustering was used to identify molecular SLE subgroups. We identified Interferon regulating factor 5 (IRF5), solute carrier family 22 member 2 (SLC22A2) and S100 calcium binding protein A12 (S100A12) as the three proteins with the largest fold change between SLE patients and controls (SLE/Control = 1.4, 1.4, and 1.2 respectively). The lowest p-values comparing SLE patients and controls were obtained for S100A12, Matrix metalloproteinase-1 (MMP1) and SLC22A2 (p(adjusted) = 3 x 10(-9), 3 x 10(-6), and 5 x 10(-6) respectively). In a set of 15 potential biomarkers differentiating SLE patients and controls, two of the proteins were transcription factors, i.e., IRF5 and SAM pointed domain containing ETS transcription factor (SPDEF). IRF5 was up-regulated while SPDEF was found to be down-regulated in SLE patients. Unsupervised clustering of all investigated proteins identified three molecular subgroups among SLE patients, characterized by (1) high levels of rheumatoid factor-IgM, (2) low IRF5, and (3) high IRF5. IRF5 expressing microparticles were analyzed by flow cytometry in a subset of patients to confirm the presence of IRF5 in plasma and detection of extracellular IRF5 was further confirmed by immunoprecipitation-mass spectrometry (IP-MS). Interestingly IRF5, a known genetic risk factor for SLE, was detected extracellularly and suggested by unsupervised clustering analysis to differentiate between SLE subgroups. Our results imply a set of circulating molecules as markers of possible pathogenic importance in SLE. We believe that these findings could be of relevance for understanding the pathogenesis and diversity of SLE, as well as for selection of patients in clinical trials.

  • 92.
    Idborg, Helena
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden..
    Zandian, Arash
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sandberg, Ann-Sofi
    Sci Life Lab, Dept Oncol Pathol, Clin Prote Mass Spectrometry, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Nilsson, Bo
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Elvin, Kerstin
    Karolinska Inst, Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Unit Clin Immunol, Stockholm, Sweden..
    Truedsson, Lennart
    Lund Univ, Dept Lab Med, Sect Microbiol Immunol & Glycobiol, Lund, Sweden..
    Sohrabian, Azita
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Ronnelid, Johan
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Mo, John
    AstraZeneca R&D, Patient Safety Resp Inflammat Autoimmun Infect &, Gothenburg, Sweden..
    Grosso, Giorgia
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden..
    Kvarnström, Marika
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden..
    Gunnarsson, Iva
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden..
    Lehtio, Janne
    Sci Life Lab, Dept Oncol Pathol, Clin Prote Mass Spectrometry, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Nilsson, Peter
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Svenungsson, Elisabet
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden..
    Jakobsson, Per-Johan
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, S-17176 Stockholm, Sweden..
    Two subgroups in systemic lupus erythematosus with features of antiphospholipid or Sjogren's syndrome differ in molecular signatures and treatment perspectives2019In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 21, article id 62Article in journal (Refereed)
    Abstract [en]

    BackgroundPrevious studies and own clinical observations of patients with systemic lupus erythematosus (SLE) suggest that SLE harbors distinct immunophenotypes. This heterogeneity might result in differences in response to treatment in different subgroups and obstruct clinical trials. Our aim was to understand how SLE subgroups may differ regarding underlying pathophysiology and characteristic biomarkers.MethodsIn a cross-sectional study, including 378 well-characterized SLE patients and 316 individually matched population controls, we defined subgroups based on the patients' autoantibody profile at inclusion. We selected a core of an antiphospholipid syndrome-like SLE (aPL+ group; positive in the lupus anticoagulant (LA) test and negative for all three of SSA (Ro52 and Ro60) and SSB antibodies) and a Sjogren's syndrome-like SLE (SSA/SSB+ group; positive for all three of SSA (Ro52 and Ro60) and SSB antibodies but negative in the LA test). We applied affinity-based proteomics, targeting 281 proteins, together with well-established clinical biomarkers and complementary immunoassays to explore the difference between the two predefined SLE subgroups.ResultsThe aPL+ group comprised 66 and the SSA/SSB+ group 63 patients. The protein with the highest prediction power (receiver operating characteristic (ROC) area under the curve=0.89) for separating the aPL+ and SSA/SSB+ SLE subgroups was integrin beta-1 (ITGB1), with higher levels present in the SSA/SSB+ subgroup. Proteins with the lowest p values comparing the two SLE subgroups were ITGB1, SLC13A3, and CERS5. These three proteins, rheumatoid factor, and immunoglobulin G (IgG) were all increased in the SSA/SSB+ subgroup. This subgroup was also characterized by a possible activation of the interferon system as measured by high KRT7, TYK2, and ETV7 in plasma. In the aPL+ subgroup, complement activation was more pronounced together with several biomarkers associated with systemic inflammation (fibrinogen, -1 antitrypsin, neutrophils, and triglycerides).ConclusionsOur observations indicate underlying pathogenic differences between the SSA/SSB+ and the aPL+ SLE subgroups, suggesting that the SSA/SSB+ subgroup may benefit from IFN-blocking therapies while the aPL+ subgroup is more likely to have an effect from drugs targeting the complement system. Stratifying SLE patients based on an autoantibody profile could be a way forward to understand underlying pathophysiology and to improve selection of patients for clinical trials of targeted treatments.

  • 93.
    Iglesias, Maria Jesus
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Bruzelius, M.
    Hong, M-Gwan
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Tregouet, D. A.
    Perisic, L.
    Frånberg, M.
    Parini, P.
    Ganna, A.
    Ingelsson, E.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hedin, U.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Silveira, A.
    Morange, P. E.
    Hamsten, A.
    Schwenk, JM, Jochen
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Odeberg, Jacob
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    An affinity proteomics study for plasma biomarker candidates of cardiovascular disease in venous thromboembolism2015In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, p. 956-956Article in journal (Refereed)
  • 94. Israelsson, M.
    et al.
    Eriksson, M. E.
    Hertzberg, M.
    Aspeborg, H.
    Nilsson, Peter
    KTH, Superseded Departments, Biotechnology.
    Moritz, T.
    Changes in gene expression in the wood-forming tissue of transgenic hybrid aspen with increased secondary growth2003In: Plant Molecular Biology, ISSN 0167-4412, E-ISSN 1573-5028, Vol. 52, no 4, p. 893-903Article in journal (Refereed)
    Abstract [en]

    Transgenic lines of hybrid aspen with elevated levels of gibberellin (GA) show greatly increased numbers of xylem fibres and increases in xylem fibre length. These plants therefore provide excellent models for studying secondary growth. We have used cDNA microarry analysis to investigate how gene transcription in the developing xylem is affected by GA-induced growth. A recent investigation has shown that genes encoding lignin and cellulose biosynthetic enzymes, as well as a number of transcription factors and other potential regulators of xylogenesis, are under developmental-stage-specific transcriptional control. The present study shows that the highest transcript changes in our transgenic trees occurs in genes generally restricted to the early stages of xylogenesis, including cell division, early expansion and late expansion. The results reveal genes among those arrayed that are up-regulated with an increased xylem production, thus indicating key components in the production of wood.

  • 95. Jakobsson, P-J
    et al.
    Svenungsson, E.
    Idborg, H.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Wheelock, C.
    Gunnarsson, I.
    Trygg, J.
    Lehtio, J.
    Koistinen, I. S.
    Proteomics and metabolomics in the classification of SLE subsets2014In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, p. 95-95Article in journal (Other academic)
  • 96. Janzi, M.
    et al.
    Pan-Hammarstrom, Q.
    Fischler, B.
    Von Dobeln, U.
    Isaac, L.
    Jonsson, G.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics.
    Hammarstrom, L.
    Microarray based analysis of serum proteins in dried blood spot samples on filter paper2008In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 154, p. 43-43Article in journal (Refereed)
  • 97. Janzi, M.
    et al.
    Ödling, Jenny
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Pan-Hammarstrom, Q.
    Sundberg, Mårten
    KTH, School of Biotechnology (BIO), Proteomics. KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics. KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Hammarstrom, L.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics. KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Serum microarrays for large scale screening of protein levels2005In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 4, no 12, p. 1942-1947Article in journal (Refereed)
    Abstract [en]

    There is a great need for comprehensive proteomic analysis of large patient cohorts of plasma and serum samples to identify biomarkers of human diseases. Here we describe a new antibody-based proteomic approach involving a reverse array format where serum samples are spotted on a microarray. This enables all samples to be screened for their content of a certain serum protein in a single experiment using target-recognizing antibodies and fluorescently labeled secondary antibodies. The procedure is illustrated with the analysis of the IgA levels in 2009 spotted serum samples, and the data are compared with clinical routine measurements. The results suggest that it is possible to simultaneously screen thousands of complex clinical serum samples for their content of the relative amount of specific serum proteins of clinical relevance.

  • 98. Janzi, Magdalena
    et al.
    Kull, Inger
    Sjöberg, Ronald
    KTH, School of Biotechnology (BIO), Proteomics.
    Wan, Jinghong
    KTH, School of Biotechnology (BIO), Proteomics.
    Melen, Erik
    Bayat, Narges
    Ostblom, Eva
    Pan-Hammarstrom, Qiang
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics.
    Hammarstrom, Lennart
    Selective IgA deficiency in early life: Association to infections and allergic diseases during childhood2009In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 133, no 1, p. 78-85Article in journal (Refereed)
    Abstract [en]

    Selective IgA deficiency in early life is quite common in Caucasian populations, but it is unclear whether it increases the risk of infections and allergic diseases during childhood. Serum IgA levels were measured in 2423 children at 4 years of age in a Swedish population based birth cohort (BAMSE). Parental questionnaires were repeatedly sent out during the child's first 8 years of life, collecting information about infections and allergic diseases. 14 children (1:173) were found to be IgA deficient at 4 years of age. These children had an increased risk of pseudocroup at year 1 (p<0.01) and food hypersensitivity at year 4 (p<0.05) as compared to IgA sufficient children. No increased risk was observed in the partial IgA deficiency group. The findings suggest that selective IgA deficiency may increase the risk of parentally reported pseudocroup and food hypersensitivity during early childhood.

  • 99. Janzi, Magdalena
    et al.
    Sjöberg, Ronald
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Wan, Jinghong
    Fischler, Björn
    von Döbeln, Ulrika
    Isaac, Lourdes
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hammarström, Lennart
    Screening for C3 deficiency in newborns using microarrays.2009In: PloS one, ISSN 1932-6203, Vol. 4, no 4, p. e5321-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Dried blood spot samples (DBSS) from newborns are widely used in neonatal screening for selected metabolic diseases and diagnostic possibilities for additional disorders are continuously being evaluated. Primary immunodeficiency disorders comprise a group of more than one hundred diseases, several of which are fatal early in life. Yet, a majority of the patients are not diagnosed due to lack of high-throughput screening methods.

    METHODOLOGY/PRINCIPAL FINDINGS: We have previously developed a system using reverse phase protein microarrays for analysis of IgA levels in serum samples. In this study, we extended the applicability of the method to include determination of complement component C3 levels in eluates from DBSS collected at birth. Normal levels of C3 were readily detected in 269 DBSS from healthy newborns, while no C3 was detected in sera and DBSS from C3 deficient patients.

    CONCLUSIONS/SIGNIFICANCE: The findings suggest that patients with deficiencies of specific serum proteins can be identified by analysis of DBSS using reverse phase protein microarrays.

  • 100.
    Just, David
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Månberg, Anna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Carlström, Eva Lindholm
    Uppsala Univ, Uppsala, Sweden..
    Cunningham, Janet
    Uppsala Univ, Uppsala, Sweden..
    Nilsson, Peter
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Towards Molecular Insights Into Psychiatric Disorders Using Affinity Proteomics2018In: Schizophrenia Bulletin, ISSN 0586-7614, E-ISSN 1745-1701, Vol. 44, p. S223-S223Article in journal (Other academic)
12345 51 - 100 of 224
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