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  • 1.
    Burman, Joachim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Neurologi.
    Zhukovskaja, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Neurologi.
    Svenningsson, Anders
    Karolinska Inst, Dept Clin Sci, Danderyd Hosp, SE-17177 Stockholm, Sweden..
    Freyhult, Eva
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik.
    Wiberg, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Neurologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Cerebrospinal fluid cytokines after autologous haematopoietic stem cell transplantation and intrathecal rituximab treatment for multiple sclerosis2023Inngår i: Brain Communications, E-ISSN 2632-1297, Vol. 5, nr 1, artikkel-id fcad011Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Multiple sclerosis has been established as an inflammatory disease of the central nervous system. Many aspects of the pathophysiology are still unknown and it is presently unclear how different treatments affect the immunopathology of multiple sclerosis. In this study, we explored cytokines discriminating between individuals with multiple sclerosis and healthy controls and then how these cytokines were affected by treatment intervention with autologous haematopoietic stem cell transplantation or intrathecal rituximab. CSF from individuals with multiple sclerosis and healthy controls were analysed with a proximity extension assay to simultaneously determine the level of 92 cytokines and other inflammation-related proteins. In total, CSF from 158 multiple sclerosis patients and 53 healthy controls were analysed. Sixty-four patients with relapsing-remitting multiple sclerosis and 27 with progressive multiple sclerosis took part in a cross-sectional study and underwent lumbar puncture on a single occasion. Forty-five patients with relapsing-remitting multiple sclerosis were treated with autologous haematopoietic stem cell transplantation and underwent lumbar puncture at baseline and then at follow-up visits made at 1-, 2- and 5 years. Twenty-two patients with progressive multiple sclerosis were treated with intrathecal rituximab and followed with lumbar punctures at baseline and then at follow-up visits made at 3-, 6- and 12 months. Of the 92 studied cytokines, 16 were found to be altered in multiple sclerosis and 11 were decreased after treatment with autologous haematopoietic stem cell transplantation. None of the studied cytokines was affected by treatment with intrathecal rituximab for progressive multiple sclerosis. Some proteins were highly associated with each other. Therefore, a cluster analysis was made and then the highest-ranked protein from the four highest-ranked clusters was used for the subsequent analyses. CCL3, IL-12B, CXCL10 and IL-8 discriminated between multiple sclerosis patients and controls, but only IL-12B differed between patients with relapsing-remitting and progressive multiple sclerosis. The CSF concentrations of CCL3, IL-12B and CXCL10 were decreased after autologous haematopoietic stem cell transplantation, whereas IL-8 appeared to be unaffected by this intervention. High concentrations of IL-8 were associated with worse outcome in both treatment groups. Overall, the results suggest a profound effect of autologous haematopoietic stem cell transplantation on the inflammatory milieu of the CSF in multiple sclerosis. Burman et al. measured CSF concentrations of 92 cytokines in patients with multiple sclerosis. CCL3, IL-12B, CXCL10 and IL-8 discriminated best between patients and healthy controls. The CSF concentrations of CCL3, IL-12B and CXCL10 decreased after treatment intervention with autologous haematopoietic stem cell transplantation for relapsing-remitting multiple sclerosis.

    Fulltekst (pdf)
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  • 2.
    Elbere, Ilze
    et al.
    Latvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia.
    Silamikelis, Ivars
    Latvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia.
    Ustinova, Monta
    Latvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia.
    Kalnina, Ineta
    Latvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia.
    Zaharenko, Linda
    Latvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia.
    Peculis, Raitis
    Latvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia.
    Konrade, Ilze
    Riga East Clin Univ Hosp, 2 Hipokrata St, LV-1038 Riga, Latvia.
    Ciuculete, Diana-Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Zhukovsky, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Gudra, Dita
    Latvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia.
    Radovica-Spalvina, Ilze
    Latvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia.
    Fridmanis, Davids
    Latvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia.
    Pirags, Valdis
    Latvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Klovins, Janis
    Latvian Biomed Res & Study Ctr, Ratsupites Str 1 K-1, LV-1067 Riga, Latvia.
    Significantly altered peripheral blood cell DNA methylation profile as a result of immediate effect of metformin use in healthy individuals2018Inngår i: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 10, artikkel-id 156Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Metformin is a widely prescribed antihyperglycemic agent that has been also associated with multiple therapeutic effects in various diseases, including several types of malignancies. There is growing evidence regarding the contribution of the epigenetic mechanisms in reaching metformin's therapeutic goals; however, the effect of metformin on human cells in vivo is not comprehensively studied. The aim of our study was to examine metformin-induced alterations of DNA methylation profiles in white blood cells of healthy volunteers, employing a longitudinal study design.

    Results: Twelve healthy metformin-naive individuals where enrolled in the study. Genome-wide DNA methylation pattern was estimated at baseline, 10h and 7days after the start of metformin administration. The whole-genome DNA methylation analysis in total revealed 125 differentially methylated CpGs, of which 11 CpGs and their associated genes with the most consistent changes in the DNA methylation profile were selected: POFUT2, CAMKK1, EML3, KIAA1614, UPF1, MUC4, LOC727982, SIX3, ADAM8, SNORD12B, VPS8, and several differentially methylated regions as novel potential epigenetic targets of metformin. The main functions of the majority of top-ranked differentially methylated loci and their representative cell signaling pathways were linked to the well-known metformin therapy targets: regulatory processes of energy homeostasis, inflammatory responses, tumorigenesis, and neurodegenerative diseases.

    Conclusions: Here we demonstrate for the first time the immediate effect of short-term metformin administration at therapeutic doses on epigenetic regulation in human white blood cells. These findings suggest the DNA methylation process as one of the mechanisms involved in the action of metformin, thereby revealing novel targets and directions of the molecular mechanisms underlying the various beneficial effects of metformin.Trial registrationEU Clinical Trials Register, 2016-001092-74. Registered 23 March 2017, https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001092-74/LV.

    Fulltekst (pdf)
    fulltext
  • 3.
    Herman, Stephanie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Arvidsson McShane, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Zhukovsky, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Experimentell neurologi.
    Emami, Payam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin. Department of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Stockholm, Sweden.
    Svenningsson, Anders
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Experimentell neurologi.
    Spjuth, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Disease phenotype prediction in multiple sclerosis2023Inngår i: iScience, E-ISSN 2589-0042, Vol. 26, nr 6, artikkel-id 106906Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Progressive multiple sclerosis (PMS) is currently diagnosed retrospectively. Here, we work toward a set of biomarkers that could assist in early diagnosis of PMS. A selection of cerebrospinal fluid metabolites (n = 15) was shown to differentiate between PMS and its preceding phenotype in an independent cohort (AUC = 0.93). Complementing the classifier with conformal prediction showed that highly confident predictions could be made, and that three out of eight patients developing PMS within three years of sample collection were predicted as PMS at that time point. Finally, this methodology was applied to PMS patients as part of a clinical trial for intrathecal treatment with rituximab. The methodology showed that 68% of the patients decreased their similarity to the PMS phenotype one year after treatment. In conclusion, the inclusion of confidence predictors contributes with more information compared to traditional machine learning, and this information is relevant for disease monitoring.

    Fulltekst (pdf)
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  • 4. Kvistad, Silje Agnethe Stokke
    et al.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lehmann, Anne Kristine
    Tolf, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Zjukovskaja, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melve, Guro Kristin
    Bø, Lars
    Torkildsen, Øivind
    Impact of previous disease-modifying treatment on safety and efficacy in patients with MS treated with AHSCT2022Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 93, nr 8, s. 844-848Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Autologous haematopoietic stem cell transplantation (AHSCT) is a highly effective treatment for multiple sclerosis (MS). The impact of previous long-lasting disease-modifying treatments (DMT) for safety and efficacy of AHSCT is unknown.

    Objective: To explore whether previous DMTs with long-lasting effects on the immune system (anti-CD20 therapy, alemtuzumab and cladribine) affect treatment-related complications, long-term outcome and risk of new MS disease activity in patients treated with AHSCT.

    Methods: Retrospective observational study of 104 relapsing remitting patients with MS treated by AHSCT in Sweden and Norway from 2011 to 2021, grouped according to the last DMT used ≤6 months prior to AHSCT. The primary outcomes were early AHSCT-related complications (mortality, neutropenic fever and hospitalisation length), long-term complications (secondary autoimmunity) and proportion of patients with No Evidence of Disease Activity (NEDA-3 status): no new relapses, no MRI activity and no disease progression during the follow-up.

    Results: The mean follow-up time was 39.5 months (range 1-95). Neutropenic fever was a common AHSCT-related complication affecting 69 (66%) patients. There was no treatment-related mortality. During the follow-up period, 20 patients (19%) were diagnosed with autoimmunity. Occurrence of neutropenic fever, hospitalisation length or secondary autoimmunity did not vary dependent on the last DMT used prior to AHSCT. A total of 84 patients (81%) achieved NEDA-3 status, including all patients (100%) using rituximab, alemtuzumab or cladribine before AHSCT.

    Conclusion: This study provides level 4 evidence that AHSCT in patients previously treated with alemtuzumab, cladribine or rituximab is safe and efficacious.

    Fulltekst (pdf)
    fulltext
  • 5.
    Olivo, Gaia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Swenne, Ingemar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnendokrinologisk forskning.
    Zhukovsky, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Tuunainen, Anna-Kaisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Saaid, Avista
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Salonen-Ros, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Barn- och ungdomspsykiatri.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Brooks, Samantha J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi. Univ Cape Town, Dept Human Biol, Cape Town, South Africa;Res Ctr Brain & Behav, Sch Nat Sci & Psychol, Liverpool, Merseyside, England.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Preserved white matter microstructure in adolescent patients with atypical anorexia nervosa2019Inngår i: International Journal of Eating Disorders, ISSN 0276-3478, E-ISSN 1098-108X, Vol. 52, nr 2, s. 166-174Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Patients with atypical anorexia nervosa (AN) are often in the normal-weight range at presentation; however, signs of starvation and medical instability are not rare. White matter (WM) microstructural correlates of atypical AN have not yet been investigated, leaving an important gap in our knowledge regarding the neural pathogenesis of this disorder.

    Method: We investigated WM microstructural integrity in 25 drug-naive adolescent patients with atypical AN and 25 healthy controls, using diffusion tensor imaging (DTI) with a tract-based spatial statistics (TBSS) approach. Psychological variables related to the eating disorder and depressive symptoms were also evaluated by administering the eating disorder examination questionnaire (EDE-Q) and the Montgomery-angstrom sberg depression rating scale (MADRS-S) respectively, to all participants.

    Results: Patients and controls were in the normal-weight range and did not differ from the body mass index standard deviations for their age. No between groups difference in WM microstructure could be detected.

    Discussion: Our findings support the hypothesis that brain structural alterations may not be associated to early-stage atypical AN. These findings also suggest that previous observations of alterations in WM microstructure in full syndrome AN may constitute state-related consequences of severe weight loss. Whether the preservation of WM structure is a pathogenetically discriminant feature of atypical AN or only an effect of a less severe nutritional disturbance, will have to be verified by future studies on larger samples, possibly directly comparing AN and atypical AN.

    Fulltekst (pdf)
    fulltext
  • 6.
    Olivo, Gaia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Swenne, Ingemar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnendokrinologisk forskning.
    Zhukovsky, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Tuunainen, Anna-Kaisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Salonen-Ros, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Barn- och ungdomspsykiatri.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Gaudio, Santino
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi. Univ Campus Biomed Roma, Ctr Integrated Res, Area Diagnost Imaging, Rome, Italy.
    Brooks, Samantha J.
    Univ Cape Town, Dept Human Biol, Cape Town, South Africa.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Reduced resting-state connectivity in areas involved in processing of face-related social cues in female adolescents with atypical anorexia nervosa2018Inngår i: Translational Psychiatry, E-ISSN 2158-3188, Vol. 8, artikkel-id 275Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Atypical anorexia nervosa (AN) has a high incidence in adolescents and can result in significant morbidity and mortality. Neuroimaging could improve our knowledge regarding the pathogenesis of eating disorders (EDs), however research on adolescents with EDs is limited. To date no neuroimaging studies have been conducted to investigate brain functional connectivity in atypical AN. We investigated resting-state functional connectivity using 3 T MRI in 22 drug-naive adolescent patients with atypical AN, and 24 healthy controls. Psychological traits related to the ED and depressive symptoms have been assessed using the Eating Disorders Examination Questionnaire (EDE-Q) and the Montgomery-Asberg Depression Rating Scale self-reported (MADRS-S) respectively. Reduced connectivity was found in patients in brain areas involved in face-processing and social cognition, such as the left putamen, the left occipital fusiform gyrus, and specific cerebellar lobules. The connectivity was, on the other hand, increased in patients compared with controls from the right inferior temporal gyrus to the superior parietal lobule and superior lateral occipital cortex. These areas are involved in multimodal stimuli integration, social rejection and anxiety. Patients scored higher on the EDE-Q and MADRS-S questionnaires, and the MADRS-S correlated with connectivity from the right inferior temporal gyrus to the superior parietal lobule in patients. Our findings point toward a role for an altered development of socio-emotional skills in the pathogenesis of atypical AN. Nonetheless, longitudinal studies will be needed to assess whether these connectivity alterations might be a neural marker of the pathology.

    Fulltekst (pdf)
    FULLTEXT01
  • 7.
    Olivo, Gaia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Schiöth: Funktionell farmakologi.
    Zhukovsky, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Schiöth: Funktionell farmakologi.
    Salonen-Ros, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Barn- och ungdomspsykiatri.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Brooks, Samantha
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Schiöth: Funktionell farmakologi. Department of Human Biology, University of Cape Town, Cape Town, South Africa; School of Natural Sciences and Psychology, Research Centre for Brain & Behaviour, Byrom Street, Liverpool, UK.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Schiöth: Funktionell farmakologi. Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
    Functional connectivity underlying hedonic response to food in female adolescents with atypical AN: The role of somatosensory and salience networks2019Inngår i: Translational Psychiatry, E-ISSN 2158-3188, Vol. 9, artikkel-id 276Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Atypical Anorexia Nervosa (AN) usually occurs during adolescence. Patients are often in the normal-weight range at diagnosis, however they often present with signs of medical complications and severe restraint over eating, body dissatisfaction, and low self-esteem. We investigated functional circuitry underlying the hedonic response in 28 female adolescent patients diagnosed with atypical AN and 33 healthy controls. Participants were shown images of food with high (HC) or low (LC) caloric content in alternating blocks during functional MRI. The HC > LC contrast was calculated. Based on previous literature on full-threshold AN, we hypothesized that patients would exhibit increased connectivity in areas involved in sensory processing and bottom-up responses, coupled to increased connectivity from areas related to top-down inhibitory control, compared with controls. Patients showed increased connectivity in pathways related to multimodal somatosensory processing and memory retrieval. The connectivity was on the other hand decreased in patients in salience and attentional networks, and in a wide cerebello-occipital network. Our study was the first investigation of food-related neural response in atypical AN. Our findings support higher somatosensory processing in patients in response to HC food images compared with controls, however HC food was less efficient than LC food in engaging patients’ bottom-up salient responses, and was not associated with connectivity increases in inhibitory control regions. These findings suggest that the psychopathological mechanisms underlying food restriction in atypical AN differ from full-threshold AN. Elucidating the mechanisms underlying the development and maintenance of eating behaviour in atypical AN might help designing specific treatment strategies.

    Fulltekst (pdf)
    fulltext
  • 8.
    Pavlovic, Ivan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Experimentell neurologi.
    Zjukovskaja, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Experimentell neurologi.
    Hayat Nazir, Faisal
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Experimentell neurologi.
    Müller, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Experimentell neurologi.
    Wiberg, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Neurologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Experimentell neurologi.
    Cerebrospinal fluid mtDNA concentrations are increased in multiple sclerosis and were normalized after intervention with autologous hematopoietic stem cell transplantation2024Inngår i: Multiple Sclerosis and Related Disorders, ISSN 2211-0348, E-ISSN 2211-0356, Vol. 84, artikkel-id 105482Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Mitochondrial DNA (mtDNA) is a pro-inflammatory damage-associated molecular pattern molecule and could be an early indicator for inflammation and disease activity in MS. Autologous hematopoietic stem cell transplantation (aHSCT) is a potent treatment for MS, but its impact on mtDNA levels in cerebrospinal fluid (CSF) remains unexplored.

    Objectives

    To verify elevated CSF mtDNA concentrations in MS patients and assess the impact of aHSCT on mtDNA concentrations.

    Methods

    Multiplex droplet digital PCR (ddPCR) was used to quantify mtDNA and nuclear DNA in 182 CSF samples. These samples were collected from 48 MS patients, both pre- and post-aHSCT, over annual follow-ups, and from 32 healthy controls.

    Results

    CSF ccf-mtDNA levels were higher in patients with MS, correlated to multiple clinical and analytical factors and were normalized after intervention with aHSCT. Differences before aHSCT were observed with regard to MRI-lesions, prior treatment and number of relapses in the last year prior to aHSCT.

    Conclusion

    Our findings demonstrate elevated CSF mtDNA levels in MS patients, which correlate with disease activity and normalize following aHSCT. These results position mtDNA as a potential biomarker for monitoring inflammatory activity and response to treatment in MS.

    Fulltekst (pdf)
    fulltext
  • 9.
    Silfverberg, Thomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Zjukovskaja, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Experimentell neurologi.
    Ljungman, Per
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden.;Karolinska Univ, Karolinska Comprehens Canc Ctr, Dept Cellular Therapy & Allogene Stem Cell Transpl, Hosp Huddinge, Stockholm, Sweden..
    Nahimi, Adjmal
    Skane Univ Hosp, Dept Neurol Rehabil Med Memory Disorders & Geriatr, Lund, Sweden..
    Ahlstrand, Erik
    Örebro Univ, Fac Med & Hlth, Dept Med, Örebro, Sweden..
    Dreimane, Arta
    Linköping Univ Hosp, Dept Hematol, Linköping, Sweden..
    Einarsdottir, Sigrun
    Univ Gothenburg, Inst Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Hematol & Coagulat, Gothenburg, Sweden..
    Fagius, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Neurologi.
    Iacobaeus, Ellen
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden..
    Hägglund, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi. Karolinska Univ, Karolinska Comprehens Canc Ctr, Dept Cellular Therapy & Allogene Stem Cell Transpl, Hosp Huddinge, Stockholm, Sweden..
    Lange, Niclas
    Örebro Univ, Fac Med & Hlth, Dept Med, Örebro, Sweden..
    Lenhoff, Stig
    Skane Univ Hosp Lund, Dept Hematol Oncol & Radiophys, Lund, Sweden..
    Lycke, Jan
    Sahlgrens Acad, Dept Clin Neurosci, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Mellergård, Johan
    Linköping Univ, Dept Neurol, Linköping, Sweden.;Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Piehl, Fredrik
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden..
    Svenningsson, Anders
    Karolinska Inst, Dept Clin Sci, Institutionen Kliniska Vetenskaper, Danderyds Sjukhus, Stockholm, Sweden.;Karolinska Inst, Dept Neurol, Institutionen Kliniska Vetenskaper, Danderyds Sjukhus, Stockholm, Sweden..
    Tolf, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Experimentell neurologi.
    Cherif, Honar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Carlson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Experimentell neurologi.
    Haematopoietic stem cell transplantation for treatment of relapsing-remitting multiple sclerosis in Sweden: an observational cohort study2024Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 95, nr 2, s. 125-133Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background A growing evidence base supports the use of autologous haematopoietic stem cell transplantation (aHSCT) for treatment of relapsing-remitting multiple sclerosis (RRMS), but it has not yet been integrated into most national clinical guidelines. The objective of this study was to assess efficacy and safety when aHSCT is implemented in routine healthcare.

    Methods We assessed 231 patients and the final analysis included 174 RRMS patients who were treated with aHSCT in Sweden before 1 January 2020. Efficacy was evaluated by performing a retrospective analysis of prospectively collected data from the Swedish MS registry. Procedure-related safety was assessed by analysing data from electronic patient records covering a period of 100 days following aHSCT.

    Results With a median follow-up time of 5.5 (IQR: 3.4–7.5) years, the Kaplan-Meier estimate for no evidence of disease activity was 73% (95% CI 66% to 81%) at 5 years and 65% (95% CI 57% to 75%) at 10 years. Out of the 149 patients with baseline disability, 80 (54%) improved, 55 (37%) were stable and 14 (9%) deteriorated. The mean number of adverse events per patient was 1.7 (±SD: 1.5) for grade 3 events and 0.06 (±SD: 0.3) for grade 4 events. Febrile neutropenia was the most common adverse event, affecting 68% of patients. There was no treatment-related mortality.

    Conclusions Treatment with aHSCT for RRMS is associated with freedom from disease activity in a majority of patients, with acceptable adverse events. This procedure should be considered a standard of care for patients with highly active RRMS.

    Fulltekst (pdf)
    FULLTEXT01
  • 10.
    Sjölin, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Neurologi.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Freyhult, Eva
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Zhukovsky, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Neurologi.
    Alkass, Kanar
    Forensic Medicine Laboratory, Department of Oncology-Pathology, Karolinska Institute, 171 77, Stockholm, Sweden..
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Neurologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Distribution of five clinically important neuroglial proteins in the human brain.2022Inngår i: Molecular brain, ISSN 1756-6606, Vol. 15, nr 1, artikkel-id 52Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), neurofilament light chain (NFL), tau and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are five neuroglial proteins that are used as CSF or blood biomarkers of tissue damage in the nervous system. There is incomplete knowledge of how the concentration of these proteins differs between anatomical regions in the CNS as previous studies have focused on gene expression or non-quantitative protein analyses, limiting the interpretability of these biomarkers. The purpose of this study was to create a map of the tissue content of these proteins in different regions of the CNS. The concentrations of the investigated proteins were determined with ELISA in post mortem tissue homogenates from 17 selected anatomical regions in the CNS from ten deceased donors aged 24 to 50 years. When appropriate, the protein concentrations were adjusted for post-mortem interval. In total, 168 tissue samples were analysed. There was a substantial variation in the concentrations of GFAP, MBP, NFL, tau and UCHL1 between different CNS regions. Highly myelinated areas of the CNS had tenfold higher MBP concentration than cerebral cortex, whereas tau showed an inverse pattern. GFAP, NFL and tau displayed an anteroposterior gradient in cerebral white matter. The cerebellum had low concentrations of all the investigated proteins. In conclusion, the tissue concentrations of GFAP, MBP, NFL, tau and UCHL1 were determined throughout the CNS. This information can be used as a reference when interpreting circulating levels of these biomarkers in relation to the extent and localisation of CNS-damaging processes.

    Fulltekst (pdf)
    fulltext
  • 11.
    Zhukovsky, Christina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Landtblom: Neurologi.
    Herman, Stephanie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Wiberg, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Cunningham, Janet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Cervenka: Psykiatri.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Landtblom: Neurologi.
    Urokinase, CX3CL1, CCL2, TRAIL and IL-18 induced by interferon-β treatment2021Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 143, nr 6, s. 602-607Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective

    To identify serum proteins associated with MS and affected by interferon beta treatment.

    Methods

    Plasma samples from 29 untreated relapsing-remitting MS patients and 15 healthy controls were investigated with a multiplexed panel containing 92 proteins related to inflammation. Follow-up samples were available from 13 patients at 1 and 3 months after initiation of treatment with interferon beta-1a.

    Results

    Ten proteins were differentially expressed in MS patients. Five of these were altered by treatment with IFN-β 1a: uPA, CX3CL1, CCL2, TRAIL and IL18.

    Conclusion

    CCL2 and TRAIL were confirmed to be modulated with interferon beta treatment in MS. As novel findings, we now report that uPA and CX3CL1 were differentially expressed in MS and increased after IFN-beta-1a treatment. Conflicting results have been reported on how interferon beta affects IL-18.

    Fulltekst (pdf)
    fulltext
  • 12.
    Zhukovsky, Christina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Cherif, Honar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Biomarkers of demyelination and axonal damage are decreased after autologous hematopoietic stem cell transplantation for multiple sclerosis2022Inngår i: Multiple Sclerosis and Related Disorders, ISSN 2211-0348, E-ISSN 2211-0356, Vol. 68, artikkel-id 104210Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) has seen increased use for relapsing-remitting multiple sclerosis (RRMS) in recent years. It is considered one of the most effective treatments for RRMS and has been associated with improvement in disability and prolonged remission. This suggests that the tissue-injuring disease process may have been altered by aHSCT. To assess whether this hypothesis is correct, we performed a study of three commonly used cerebrospinal fluid biomarkers of tissue damage.

    METHODS: In this single center study, 63 patients treated with aHSCT at Uppsala University Hospital between January 1st 2012 and January 31st 2019 were screened for participation. A control group consisting of volunteers without neurologic disease were included as a reference. Cerebrospinal fluid concentrations of neurofilament light (NFL), myelin basic protein (MBP) and glial acidic fibrillary protein (GFAp) were determined using ELISA and a multiplex proteomics platform from Meso Scale Discovery.

    RESULTS: Forty-three patients with a mean age of 31 and a median follow-up time of 3.9 years were included. Their median baseline expanded disability status scale (EDSS) score was 3.5 and the annualized relapse rate in the year preceding aHSCT was 1.6. At baseline the proportion of patients with values above the upper limit of normal was 67% for NFL, 63% for MBP and 16% for GFAp. At 5-year follow-up, the proportion of patients with values above the upper limit of normal was 12% for NFL, 12% for MBP and 25% for GFAp. The mean concentration of NFL decreased from 920 pg/mL at baseline to 270 pg/mL at 5-year follow-up (p < 0.001); MBP decreased from 1500 to 680 pg/mL (p < 0.001); whereas the mean concentration of GFAp was unchanged.

    CONCLUSION: In a majority of patients, biomarkers of demyelination and axonal damage reached normal values within five years from treatment with aHSCT.

    Fulltekst (pdf)
    fulltext
  • 13.
    Zhukovsky, Christina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Landtblom: Neurologi.
    Sandgren, Sofia
    Sahlgrens Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, Gothenburg, Sweden..
    Silfverberg, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Einarsdottir, Sigrun
    Sahlgrens Univ Hosp, Dept Hematol & Coagulat, Gothenburg, Sweden..
    Tolf, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Landtblom: Neurologi.
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Landtblom: Neurologi.
    Novakova, Lenka
    Sahlgrens Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, Gothenburg, Sweden..
    Axelsson, Markus
    Sahlgrens Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, Gothenburg, Sweden..
    Malmestrom, Clas
    Sahlgrens Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, Gothenburg, Sweden..
    Cherif, Honar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Carlson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Lycke, Jan
    Sahlgrens Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, Gothenburg, Sweden..
    Burman, Joachim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Landtblom: Neurologi.
    Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing-remitting multiple sclerosis: an observational study2021Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 92, nr 2, s. 189-194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To compare outcomes after treatment with autologous haematopoietic stem cell transplantation (AHSCT) and alemtuzumab (ALZ) in patients with relapsing-remitting multiple sclerosis.

    Methods: Patients treated with AHSCT (n=69) received a conditioning regimen of cyclophosphamide (200 mg/ kg) and rabbit anti-thymocyte globulinerG (6.0 mg/kg). Patients treated with ALZ (n=75) received a dose of 60 mg over 5 days, a repeated dose of 36 mg over 3 days after 1 year and then as needed. Follow-up visits with assessment of the expanded disability status scale score, adverse events and MR investigations were made at least yearly.

    Results: The Kaplan-Meier estimates of the primary outcome measure 'no evidence of disease activity' was 88% for AHSCT and 37% for ALZ at 3 years, p<0.0001. The secondary endpoint of annualised relapse rate was 0.04 for AHSCT and 0.1 for ALZ, p=0.03. At last follow-up, the proportions of patients who improved, were stable or worsened were 57%/41%/1% (AHSCT) and 45%/43%/12% (ALZ), p=0.06 Adverse events grade three or higher were present in 48/69 patients treated with AHSCT and 0/75 treated with ALZ in the first 100 days after treatment initiation. The most common long-term adverse event was thyroid disease with Kaplan-Meier estimates at 3 years of 21% for AHSCT and 46% for ALZ, p=0.005.

    Conclusions: In this observational cohort study, treatment with AHSCT was associated with a higher likelihood of maintaining 'no evidence of disease activity'. Adverse events were more frequent with AHSCT in the first 100 days, but thereafter more common in patients treated with ALZ.

    Fulltekst (pdf)
    fulltext
  • 14.
    Zjukovskaja, Christina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Neurologi.
    Hematopoietic Stem Cell Transplantation for Treatment of Multiple Sclerosis in Sweden2023Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis investigated the efficacy and safety of autologous hematopoietic stem cell transplantation (AHSCT) as a treatment of multiple sclerosis. 

    This thesis demonstrates that when compared to one of the most powerful disease-modifying drugs (DMDs), specifically alemtuzumab (ALZ), AHSCT is able to hold its ground. Patients that were treated with AHSCT were more likely to maintain NEDA-3 or freedom from disease in three parameters (no confirmed disability worsening, clinical relapses or MRI events) versus those treated with ALZ. The three year post-treatment Kaplan-Meier (KM) estimates of NEDA-3 were 88 % for AHSCT and 37 % for ALZ treated patients.  With AHSCT, adverse events were more common in the first three months, as is expected with an intense one-time treatment. ALZ, though powerful and with little early adverse effects, has more late adverse effects instead, namely thyroid disease. At 3 years post-treatment, the KM-estimates of thyroid disease were 21 % for AHSCT and 46 % for ALZ. We then sought to address potential concerns in using AHSCT on patients previously treated with potent DMDs like alemtuzumab, cladribine or rituximab. The concern lay in the fact that these powerful DMDs have long-lasting effects on the immune system. We found that the rates of treatment-related and long-term complications were the same for all patients regardless of previous use of DMDs. This finding therefore allays those concerns: previous treatment with a powerful DMDs need no longer be a possible deterrent to giving a patient AHSCT.

    Using a series of CSF biomarker studies, we gauged treatment efficacy. We showed that CNS inflammation is measurably affected by treatment, especially when it comes to AHSCT. Post-AHSCT treatment, many of the proteins we studied decreased towards the direction of healthy individuals, as early as the first year after treatment and remained so during subsequent follow-ups. Additionally we saw that tissue-injuring disease processes, for example represented by biomarkers like NFL and MBP, normalized for the majority of patients. These promising results suggest that tissue-injury could possibly be stopped in its tracks with AHSCT.  Finally, we observed that biomarkers of B- and T-cell activation also became normalized, showing that AHSCT treatment also shuts down acute inflammation. All of these factors together explain why patients treated with AHSCT are able to maintain NEDA-3 so effectively even when compared to one of the most potent drugs available. These results compellingly illustrate that AHSCT treatment yields quantifiably long-lasting and beneficial effects that are not commonly seen with other available treatments for MS. Therefore, use of AHSCT should be advocated, promoted and utilized more for the benefit of patients and society as a whole.

    Fulltekst (pdf)
    UUThesis_C-Zjukovskaja-2023
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