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  • 101.
    Svärd, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Kastbom, Alf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Sommarin, Yngve
    EuroDiagnostica AB, Malmö.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    A disease-modifying role for mucosal IgA antibodies to citrullinated antigens?2012Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, nr Issue suppl. 1, s. A38-A39Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    The aim of this study was to investigate whether immunoglobulin A (IgA) antibodies to cyclic citrullinated peptides CCP) can be detected in saliva of patients with established heumatoid arthritis (RA) and if it relates to clinical manifestations.

    Methods

    Salivary samples were collected (by ‘passive drooling’) from 63 consecutive patients with established RA at a visit to the rheumatology outpatient clinic (Falun, Sweden), and from 20 healthy persons (hospital staff). The samples were centrifuged and kept frozen at −70°C until analysis. IgA-class anti-CCP antibodies in saliva were analysed by adaptation of commercial ELISA (Immunoscan RA, Euro-Diagnostica AB, Malmo, Sweden) using polyclonal rabbit antihuman α-chain specific antibodies conjugated with horseradish peroxidase(DakoCytomation, Glostrup, Denmark) as secondary antibody. To ensure specificity of the reaction, a corresponding ELISA was set up to analyse IgA antibodies to control antigen(cyclic arginine peptide, CAP), and anti-CCP/anti-CAP ratios were calculated. Also, inhibition studies were performed by preincubation of sera with soluble CCP or CAP. Clinical and laboratory data on disease activity, that is, C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and 28-joint count disease activity score (DAS28) as well as radiological outcome (occurrence or absence of erosions as judged by a radiologist in diagnostic routine) were achieved retrospectively via the patients’ medical records.

    Results

    Background reactivity against CCP was found in virtually all patients and healthy subjects, whereas a positive anti-CCP/anti-CAP ratio (≥1.5) was found in 14 out of 63 RA patients (22%) and in one healthy subject (5%). Salivary IgA-reactivity with CCP was dose-dependently inhibited by soluble CCP (but not with CAP) in sera with anti-CCP/anti- CAP ratios ≥1.5. No IgG-reactivity to CCP was found in saliva, although all patients with salivary IgA anti-CCP tested IgG anti-CCP-positive in serum. Furthermore, less than half of those testing IgA-positive in saliva were IgA anti-CCP positive in serum, strongly arguing against passive leakage of anti-CCP antibodies from blood to saliva. The patients testing positive for salivary IgA antibodies had lower average disease activity measures (CRP, ESR, DAS28) at presentation and fewer developed bony erosions within 6 years after presentation (p=0.043, Fisher’s exact test).

    Conclusion

    Salivary IgA antibodies to citrullinated proteins were found in a subset of IgG anti-CCP positive RA patients. In contrast to their serum counterparts, salivary IgA antibodies may associate with a milder/less destructive disease course. This accords with the notion that secretory IgA antibodies exert anti-inflammatory actions, and that they may be associated with induction of systemic tolerance (oral tolerance). The possible disease-modifying role of mucosal immunity to citrullinated proteins needs further investigation!

                    

                                                                    

  • 102.
    Svärd, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Kastbom, Alf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Sommarin, Yngve
    Eurodiagnostica AB.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    A Disease-Modifying Role for Mucosal IgA Antibodies to Citrullinated Antigens? in ARTHRITIS AND RHEUMATISM, vol 63, issue 10, pp S849-S8492011Ingår i: ARTHRITIS AND RHEUMATISM, Wiley-Blackwell , 2011, Vol. 63, nr 10, s. S849-S849Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 103.
    Svärd, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Kastbom, Alf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Sommarin, Yngve
    Euro-Diagnostica AB, Malmö, Sweden.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis2013Ingår i: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 218, nr 2, s. 232-237Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Circulating IgG anti-cyclic citrullinated peptide antibodies (CCP) are highly specific for rheumatoid arthritis (RA) and prognostic of poor outcome. Serum IgA anti-CCP occurs in a subset of IgG-positive cases and relates to still more aggressive disease. Mucosal IgA-class antibodies, however, are generally associated with anti-inflammatory actions and systemic tolerance induction. In the present study, unstimulated salivary samples from 63 patients with established RA and 20 healthy persons were analysed by enzyme-linked immunoassay for the presence of IgA anti-CCP antibodies. To ensure antigen specificity, IgA-reactivity with the corresponding uncitrullinated antigen, cyclic arginine peptide (CAP), was analysed and anti-CCP/anti-CAP ratios calculated. Retrospective data regarding disease activity and radiological outcome were achieved via medical records. Salivary IgA anti-CCP was found in 14/63 (22%) patients and one (5%) control (positive test = anti-CCP/anti-CAP ratio andgt; 1.5). Salivary IgA reactivity was dose-dependently inhibited by pre-incubation with soluble CCP to a degree strongly correlating with anti-CCP/anti-CAP ratio. In salivary IgA anti-CCP positive patients, joint erosions within 6 years of diagnosis was significantly lower (p = 0.043), and at the time for diagnosis there was a trend towards lower erythrocyte sedimentation rate (p = 0.071) and C-reactive protein (p = 0.085). Contrasting to circulating IgG and IgA anti-CCP, our results imply that salivary IgA antibodies may be associated with a less severe outcome of RA. Hypothetically, this relates to an anti-inflammatory and protective immunomodulating role of secretory IgA-class autoantibodies against citrullinated antigens presented at mucosal surfaces.

  • 104.
    Svärd, Anna
    et al.
    Rheumatology Clinic, Falun Hospital, Falun.
    Kastbom, Alf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Söderlin, Maria K.
    Spenshult Rheumatology Centre, Oskarström, Sweden.
    Reckner-Olsson, Åsa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    A Comparison Between IgG- and IgA-class Antibodies to Cyclic Citrullinated Peptides and to Modified Citrullinated Vimentin in Early Rheumatoid Arthritis and Very Early Arthritis2011Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 38, nr 7, s. 1265-1272Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. Because of their slightly higher sensitivity, it has been argued that antibodies to modified citrullinated vimentin (anti-MCV) are superior to antibodies to cyclic citrullinated peptides (anti-CCP), while others claim that anti-CCP is preferable because of higher diagnostic specificity for rheumatoid arthritis (RA). We evaluated IgG- and IgA-class anti-MCV and anti-CCP as diagnostic and prognostic markers in early arthritis. less thanbrgreater than less thanbrgreater thanMethods. Two Swedish arthritis populations were examined: 215 patients with early RA (andlt;= 12 months duration) from the Swedish TIRA-1 cohort, and 69 patients with very early arthritis (andlt;= 3 months duration) from the Kronoberg Arthritis Incidence cohort, in which 22% were diagnosed with RA. IgG anti-CCP and anti-MCV antibodies were analyzed with commercial kits. These tests were modified for IgA-class antibody detection. less thanbrgreater than less thanbrgreater thanResults were related to disease course, smoking habits, and shared epitope status. Results. In the TIRA-1 cohort, occurrence of IgG anti-MCV and IgG anti-CCP showed a 93% overlap, although IgG anti-MCV had higher diagnostic sensitivity. Twenty-four percent tested positive for IgA anti-MCV compared to 29% for IgA anti-CCP. In the Kronoberg Arthritis Incidence cohort, 15% tested positive for IgG anti-MCV and 6% for IgA anti-MCV, compared to 10% positive for IgG anti-CCP and 3% positive for IgA anti-CCP, revealing that anti-CCP had higher diagnostic specificity for RA. As previously reported for IgA anti-CCP, IgA anti-MCV antibodies occurred in a small proportion of high-level IgG antibody-positive sera and were associated with a more aggressive disease course. Smokers were more often positive for antibodies to citrullinated proteins, most strikingly among the patients who were IgA anti-MCV-positive. less thanbrgreater than less thanbrgreater thanConclusion. The occurrences of IgG-class anti-MCV and anti-CCP in early RA largely overlap. The sensitivity of anti-MCV is slightly higher, while the diagnostic specificity is higher for anti-CCP. In both instances a positive test predicts an unfavorable disease course, possibly slightly more so for anti-MCV. Although associated with a more active disease over time, IgA-class anti-CCP or anti-MCV do not add any diagnostic advantage.

  • 105.
    Söderlin, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    A population-based study on early arthritis in southern Sweden: Incidence, preceding infections, diagnostic markers and economic burden2003Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The total annual incidence of arthritis in this prospective cross-sectional study on adults was 115/100 000. The annual incidence of rheumatoid arthritis (RA) was 24/100 000, 29/100 000 for women, and 18/100 000 for men. For reactive arthritis (ReA) the annual incidence was slightly higher, 28/100 000, and for undifferentiated arthritis 41/100 000. The annual incidence of Lyme disease and sarcoid arthritis was low. The annual incidence of arthritis in this study compares well with findings in earlier reports from both registers and case review studies. Almost 50% of the patients in the series of 71 patients with arthritis of less than 3 months’ duration had a preceding infection. Campylobacter jejuni ReA dominated the enteric ReA group. We found only a few patients with preceding Chl. trachomatis, Chl. pneumoniae, Borrelia burgdorferi or parvovirus B19 infections. The arthritis patients with a preceding infection went into remission more often than the patients without a preceding infection. The disease specificity of anti-CCP antibodies for RA was high, 96%, confirming earlier results. Anti-CCP antibodies differentiated RA from other arthritides. Several patients in the different diagnosis groups had raised serum COMP levels, indicating cartilage involvement very early in the disease, even in mild and self-limiting disease with good prognosis. The economic burden of early joint inflammation was found to be considerable already during the first few months of the arthritis irrespective of diagnosis. Surprisingly, patients with ReA generated almost as high costs as patients with RA during thefirst few months of the disease, even though most of the ReA patients had a relatively mild disease. Sick leave accounted for about 50% of the costs. The distribution of costs in the different patient groups was skewed. The median cost per patient for the group of patients with RA was US$4385, for ReA US$4085, for other types of specified arthritis US$3361, and for undifferentiated arthritis US$1482. This underlines the necessity of quick referral and therapy, not only to decrease the inflammation and prevent functional impairment, but also to decrease the costs of early arthritis.

  • 106.
    Söderlin, Maria
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Börjesson, Olle
    Department of Internal Medicine, Växjö Central Hospital, Växjö, Sweden.
    Kautiainen, Hannu
    Rheumatism Foundation Hospital, Heinola, Finland.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Leirisalo-Repo, Marjatta
    Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Huch, Finland.
    Annual incidence of inflammatory joint diseases in a population based study in southern Sweden2002Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, Vol. 61, s. 911-915Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To estimate the annual incidence of inflammatory joint diseases in a population based prospective referral study in an adult population in Kronoberg County in southern Sweden.

    Methods: The patients were referred from primary healthcare centres to the rheumatology department in Växjö Central Hospital or to the one private rheumatologist in Växjö participating in the study. Additionally, the hospital records for patients with joint aspirates during the inclusion period were checked. The patients were registered as incident cases if the onset of the joint inflammation was between 1 May 1999 and 1 May 2000. A systematic follow up of incoming referrals was conducted up to 31 January 2001. Children under the age of 16 and patients with septic arthritis, crystal arthropathies, and osteoarthritis were excluded from the study.

    Results: A total of 151 new cases with inflammatory joint diseases were identified during one year, corresponding to a total annual incidence of 115/100 000. Of these, 31 patients (21%) had rheumatoid arthritis, the annual incidence being 24/100 000 (for women 29/100 000, and for men 18/100 000). Reactive arthritis was diagnosed in 37 patients (24%, annual incidence 28/100 000) and 54 patients had undifferentiated arthritis (36%, annual incidence 41/100 000). Eleven patients presented with psoriatic arthritis (7%, annual incidence 8/100 000). The incidence of Lyme arthritis was small in this non-endemic area, and the incidence of sarcoid arthritis corresponded to that in earlier studies.

    Conclusion: This is the first prospective population based annual incidence study of early arthritis in Sweden. In this population, 36% of the incident cases had undifferentiated arthritis, whereas rheumatoid arthritis and reactive arthritis accounted for 45% of the cases. The incidence figures compare well with figures reported from other countries.

  • 107.
    Söderlin, Maria
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi.
    Kastbom, Alf
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Kautiainen, H
    Leirisalo-Repo, M
    Strandberg, Gunnar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Skogh, Thomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Antibodies against cyclic citrullinated peptide (CCP) and cartilage oligomeric matrix protein (COMP) in relation to disease activity and erosions in a prospective population-based study of very early arthritis.2003Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 48, nr 9, s. 194-Konferensbidrag (Övrigt vetenskapligt)
  • 108.
    Söderlin, Maria
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Kastbom, Alf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Kautiainen, Hannu
    Rheumatism Foundation Hospital, Heinola, Finland.
    Leirisalo-Repo, Marjatta
    Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Huch, Finland.
    Strandberg, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Antibodies against cyclic citrullinated peptide (CCP) and levels of cartilage oligomeric matrix protein (COMP) in very early arthritis: relation to diagnosis and disease activity2004Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, Vol. 33, nr 3, s. 185-188Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To measure serum levels of antibodies against cyclic citrullinated peptide (anti-CCP antibodies) and serum cartilage oligomeric matrix protein (COMP) in patients with early joint inflammation, and to study the correlation of these two tests with clinical measurements.

    Methods: Adult patients with recent-onset arthritis, of <3 months' duration, were referred from primary healthcare centres to rheumatologists. Serum levels of anti-CCP antibodies and COMP at baseline were analysed by enzyme immunoassay (EIA) and compared with clinical baseline data.

    Results: Sixty-nine patients were included. The specificity of the anti-CCP antibody test for RA was 96%, and the sensitivity was 44%. There was a significant difference between the four diagnosis groups in the anti-CCP antibody test, probability (p)<0.001, whereas no significant differences were found concerning COMP. The baseline serum COMP test correlated with age (p=0.0001), joint score for swollen joints (p=0.02), and C-reactive protein (CRP) (p=0.02).

    Conclusion: This study confirms the high diagnostic specificity of anti-CCP antibodies for rheumatoid arthritis (RA) in a prospective population-based study of very early arthritis. Raised serum COMP levels were common in all diagnosis groups in this series, indicating cartilage involvement in both self-limiting and non-erosive disease.

  • 109.
    Söderlin, Maria
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Kautiainen, Hannu
    Rheumatism Foundation Hospital, Heinola, Finland.
    Puolakkainen, M.
    Hedman, K.
    Söderlund-Venermo, M.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Leirisalo-Repo, Marjatta
    Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Huch, Finland.
    Infections preceding early arthritis in southern Sweden: a prospective population-based study2003Ingår i: The Journal of Rheumatology, ISSN 0315-162X, Vol. 30, nr 3, s. 459-464Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To detect evidence of infections preceding early arthritis in Southern Sweden and to compare the clinical outcome of remission during a 6-month followup for patients with and without signs of prior infection.

    METHODS: Adult patients with arthritis of less than 3 months' duration were referred from primary health care centers to rheumatologists. All patients were systematically screened for infections caused by Salmonella typhimurium and Salmonella enteritidis, Yersinia enterocolitica, Campylobacter jejuni, Borrelia burgdorferi, Chlamydia trachomatis, Chlamydia pneumoniae, and parvovirus B19.

    RESULTS: Seventy-one patients were included in this study. Twenty-seven (38%) patients had reactive arthritis (ReA), 17 (24%) undifferentiated arthritis, 15 (21%) rheumatoid arthritis (RA), 4 (6%) psoriatic arthritis, and the rest (11%) other diagnoses. Of all the patients, 45% had evidence of a recent infection preceding the arthritis, as indicated by laboratory tests and/or disease history. C. jejuni dominated the ReA group. The occurrence of recent C. trachomatis, B. burgdorferi, C. pneumoniae, and parvovirus B19 infections was low. Overall, 58% of the patients went into remission during the 6-month followup. Of the patients with a preceding infection, 69% went into remission as compared to 38% of the patients without a preceding infection (p = 0.011). Thirty-three percent of the patients with RA were in remission after 6 months.

    CONCLUSION: In this population-based cohort, 45% of the patients presenting with a new-onset arthritis had had a prior infection. Campylobacter ReA dominated the ReA group. There were only a few cases preceded by infections by C. trachomatis, B. burgdorferi, C. pneumoniae, and parvovirus B19 infections. Remission during the first 6 months was especially frequent in the group of patients with a prior infection, but the remission rate was relatively high even for arthritis without prior infection.

  • 110.
    Söderlin, Maria
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Kautianen, Hannu
    Rheumatism Foundation Hospital, Heinola, Finland.
    Jonsson, Dick
    Linköpings universitet, Institutionen för medicin och hälsa, Medicinsk teknologiutvärdering. Linköpings universitet, Hälsouniversitetet.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Leirisalo-Repo, Marjatta
    Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Huch, Finland.
    The costs of early inflammatory joint disease: a population-based study in southern Sweden2003Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, Vol. 32, nr 4, s. 216-224Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To study the costs and use of healthcare for patients during the first months with early joint inflammation, in a population-based prospective referral study in Southern Sweden.

    Methods: Adult patients with arthritis for <3 months and with onset of symptoms between 1 May 1999 and 1 May 2000 were referred from primary health centres to rheumatologists. Four clinical assessments were performed during a 6-month follow-up period. The direct medical costs for inpatient stays, outpatient visits, visits to general practitioners, and visits to health professionals, as well as costs for medication, radiographs, and laboratory tests were recorded from the onset of the disease up to 6 months of follow-up. Indirect costs for sick leave were also recorded.

    Results: Fifty-six of 71 referred patients agreed to participate. Thirteen (23%) had RA, 21 (38%) had reactive arthritis (ReA), 14 (25%) had undifferentiated arthritis, and eight (14%) had other arthritides. The median cost per patient in the entire group was USD 3362. The median cost per patient in the RA group was USD 4385, and USD 4085 in the ReA group. There was no statistically significant difference in the median costs per patient in the different diagnostic groups. Sick leave accounted for 44% of the total costs in the entire group, and 46% and 47%, respectively, in the RA and ReA groups.

    Conclusion: The costs of early arthritis are already considerable during the first months of the disease following the onset of the symptoms. The indirect costs due to sick leave accounted for nearly half of the costs.

  • 111.
    Thyberg, Ingrid
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Dahlström, Örjan
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten.
    Björk, Mathilda
    Department of Rehabilitation, School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Arvidsson, P.
    Thyberg, Mikael
    Linköpings universitet, Institutionen för medicin och hälsa, Rehabiliteringsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Smärt och rehabiliteringscentrum.
    Potential of the HAQ score as clinical indicator suggesting comprehensive multidisciplinary assessments: the Swedish TIRA cohort 8 years after diagnosis of RA2012Ingår i: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 31, nr 5, s. 775-783Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study explores the potential of the health assessment questionnaire (HAQ) score as a clinical indicator that can be used to suggest comprehensive multidisciplinary assessments, by relating it to more general aspects of disability. In a cohort of 132 patients with early RA (mean age 55, 68% women), 28 joint count Disease Activity Scores (DAS-28), HAQ, and Short Form 36 (SF-36) scores were registered at annual follow-up visits 8 years after diagnosis. The patients were tentatively sub-grouped into a high-HAQ group (HAQ ≥1 at the 8-year follow-up) and a low-HAQ group. The high-HAQ group, comprising 36% of the cohort, had a higher mean HAQ score at inclusion and beyond at all visits compared to the low-HAQ group, and 24% of all individual patients in the high-HAQ group had a HAQ score ≥1 at inclusion. Although the DAS-28 improved in both groups, patients in the high-HAQ group also had significantly more persistent disability according to the SF-36: five scales at each follow-up visit and all eight scales at the majority of the visits. Individual RA patients with HAQ ≥1 probably have considerable persistent disabilities according to the SF-36. The HAQ score could be used as a clinical indicator suggesting comprehensive multidisciplinary assessments of the components of disability and corresponding interventions, in addition to the established use of HAQ at group levels and in parallel with the medication strategy based on DAS-28.

  • 112.
    Thyberg, Ingrid
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Dahlström, Örjan
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten.
    Björk, Mathilda
    School of Health Sciences, Jönköping University, Sweden.
    Stenström, Birgitta
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Adams, Jo
    University of Southampton, UK.
    Hand pains and general pain in women and men in early RA: a one year follow up after diagnosis in the TIRA-2 cohort2013Konferensbidrag (Övrigt vetenskapligt)
  • 113.
    Turesson, Carl
    et al.
    Skåne University Hospital.
    Cöster, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Lysholm, Jorgen
    Falun County Hospital.
    RHEUMATOID ARTHRITIS: INSIGHTS, STRATEGIES AND EXPECTATIONS?SWEDISH RESULTS OF THE RAISE PATIENT NEEDS SURVEY in SCANDINAVIAN JOURNAL OF RHEUMATOLOGY, vol 39, issue , pp 23-232010Ingår i: SCANDINAVIAN JOURNAL OF RHEUMATOLOGY, Informa Healthcare , 2010, Vol. 39, s. 23-23Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 114.
    van Vollenhoven, R.F.
    et al.
    Karolinska University Hospital.
    Ernestam, S.
    Karolinska University Hospital.
    Geborek, P.
    Lund University Hospital.
    Petersson, I.F.
    Lund University Hospital.
    Cöster, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Waltbrand, E.
    Lasarettet, Borås.
    Zickert, A.
    Danderyds Hospital.
    Theander, J.
    Centralsjukhuset, Kristianstad.
    Thorner, A.
    Mälarsjukhuset.
    Hellstrom, H.
    Lasarettet, Falun.
    Teleman, A.
    Spenshult Hospital.
    Dackhammar, C.
    University Hospital, Mölndal.
    Akre, F.
    University Hospital, Örebro.
    Forslind, K.
    Lund University Hospital.
    Ljung, L.
    University Hospital, Umeå.
    Oding, R.
    Centrallasarettet, Västerås.
    Chatzidionysiou, A.
    Karolinska University Hospital.
    Wornert, M.
    Karolinska University Hospital.
    Bratt, J.
    Karolinska University Hospital.
    Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial2009Ingår i: The Lancet, ISSN 0140-6736, Vol. 374, nr 9688, s. 459-466Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: New treatment strategies for early rheumatoid arthritis are evolving rapidly. We aimed to compare addition of conventional disease-modifying antirheumatic drugs (sulfasalazine and hydroxychloroquine) with addition of a tumour necrosis factor antagonist (infliximab) to methotrexate in patients with early rheumatoid arthritis. Methods: We undertook a randomised trial in 15 rheumatology units in Sweden. We enrolled patients with early rheumatoid arthritis (symptom duration less than1 year) and administered methotrexate (up to 20 mg per week). After 3-4 months, those who had not achieved low disease activity but who could tolerate methotrexate were randomly allocated by computer addition of either sulfasalazine and hydroxychloroquine or infliximab. Primary outcome was achievement of a good response according to European League Against Rheumatism (EULAR) criteria at 12 months. Patients were followed up to 24 months; here, we present findings at 12 months. Analysis was by intention to treat and we used non-responder imputation. The Swefot (Swedish Pharmacotherapy) study is registered in the WHO database at the Karolinska University Hospital, number CT20080004. Findings: 487 patients were initially enrolled. Of 258 who had not achieved low disease activity with methotrexate, 130 were allocated sulfasalazine and hydroxychloroquine and 128 were assigned infliximab. 32 of 130 (25%) patients allocated sulfasalazine and hydroxychloroquine achieved the primary outcome compared with 50 of 128 (39%) assigned infliximab (risk ratio 1·59 [95% CI 1·10-2·30], p=0·0160). Adverse events were balanced fairly well between the two groups and accorded with known adverse events of the drugs used. No deaths occurred in either group. Interpretation: In patients with early rheumatoid arthritis in whom methotrexate treatment failed, addition of a tumour necrosis factor antagonist to methotrexate monotherapy is clinically superior to addition of conventional disease-modifying antirheumatic drugs. Funding: Swedish Rheumatism Association, Schering-Plough.

  • 115.
    Verma, Deepti
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Eriksson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Sahdo, Berolla
    Örebro universitet, Sweden.
    Persson, Alexander
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Ejdebäck, Mikael
    Skövde universitet, Sweden.
    Särndahl, Eva
    Örebro universitet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Two adult siblings with atypical cryopyrin-associated periodic syndrome due to a novel M299V mutation in NLRP32010Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 62, nr 7, s. 2138-2143Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The NALP3 inflammasome is a multiprotein complex that triggers caspase 1-mediated interleukin-1beta (IL-1beta) release. Mutations in the gene encoding NALP3 (NLRP3) underlie the cryopyrin-associated periodic syndrome (CAPS). The aim of this study was to report a novel NLRP3 mutation in 2 siblings of Swedish descent in whom symptoms first presented in adulthood.

    METHODS: Mutation analysis of NLRP3 was performed on DNA from patients with CAPS and 100 control subjects. For assessment of caspase 1 and IL-1beta, blood was collected from patients and age- and sex-matched healthy control subjects. Genetic constructs containing mutant or wild-type NLRP3 were transduced into THP-1 cells, followed by assessment of IL-1beta levels in cell supernatant.

    RESULTS: Both siblings carried a novel M299V mutation in NLRP3, which was not present in the control population. The samples obtained from the patients displayed increased caspase 1 activity and elevated IL-1beta levels at basal conditions as compared with healthy control subjects. THP-1 cells expressing mutated M299V revealed almost 10-fold higher IL-1beta production compared with the wild-type construct.

    CONCLUSION: M299V is an activating mutation in NLRP3 resulting in elevated spontaneous caspase 1 activity and IL-1beta levels. The classic CAPS phenotype was lacking in these adult siblings. Whereas one sibling displayed a milder phenotype that has so far responded satisfactorily to oral nonsteroidal antiinflammatory drugs in combination with low-dose corticosteroids, the inflammatory symptoms in the sibling with the more severe case responded well to IL-1beta blockade. Understanding the pathogenic mechanism underlying such disorders can be helpful for the physician. Our study reinforces the importance of genetic testing and laboratory investigations in combination with careful phenotypic evaluation for the diagnosis of such patients.

  • 116.
    Verma, Deepti
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Lerm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Blomgran Julinder, Robert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Eriksson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Söderkvist, Peter
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi.
    Särndahl, Eva
    Örebro Universitet, Örebro.
    Gene polymorphisms in the NALP3 inflammasome are associated with interleukin-1 production and severe inflammation: Relation to Common Inflammatory Diseases?2008Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 58, nr 3, s. 888-894Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: NALP3, ASC, and TUCAN are components of the NALP3 inflammasome, which triggers caspase 1-mediated interleukin-1β (IL-1β) release. Activating mutations in the gene encoding NALP3 (NLRP3) have recently been linked to familial periodic fever syndromes. We undertook this study to determine whether a patient with arthritis and antibiotic-resistant fever carried mutations in the genes encoding the NALP3 inflammasome.

    Methods: Genetic analysis of NLRP3 and the gene encoding TUCAN (CARD-8) was performed on genomic DNA from the patient and from a population-based collection of DNA (806 subjects). For in vitro studies of IL-1β production and caspase 1 activity, blood was obtained from the patient at different time points after administration of anakinra, an IL-1 receptor antagonist, as well as from 5 healthy age- and sex-matched control subjects.

    Results: Mutation analysis of the patient's genes encoding NALP3, ASC, and TUCAN revealed variations in the NLRP3 (Q705K) and CARD-8 (C10X) genes. The allele frequencies of these single-nucleotide polymorphisms (SNPs) in the population were 6.5% and 34%, respectively. The elevated activity of caspase 1 and the high levels of IL-1β measured in samples from the patient returned to normal levels after treatment with anakinra.

    Conclusion: Our results indicate that the patient's symptoms were due to elevated levels of IL-1β, since treatment with anakinra effectively abolished the symptoms. The compound SNPs may explain the increased IL-1β levels and inflammatory symptoms observed, but further studies are needed to reveal a functional relationship. The prevalence of the polymorphisms (4% of the population carry both SNPs) in the general population may suggest a genetic predisposition for common inflammatory disorders.

  • 117.
    Verma, Deepti
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Lerm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Eriksson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Fredriksson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Andersson, Henrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, Jan-Ingvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell hematologi. Linköpings universitet, Hälsouniversitetet.
    Särndahl, Eva
    Department of Clinical Medicine, School of Health & Medical Sciences, Örebro University, SE-701 82 Örebro, Sweden.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    The Q705K polymorphism in NLRP3 is a gain-of-function alteration leading to excessive interleukin-1β and IL-18 production2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The Q705K polymorphism in NLRP3 has been implicated in several chronic inflammatory diseases. In this study, we determine the functional role of this commonly occurring polymorphism using an in-vitro system.

    Methods / Principle findings: NLRP3-WT and NLRP3-Q705K were retrovirally transduced into the human monocytic cell line THP-1, followed by the assessment of IL-1β and IL-18 levels in the cell culture supernatant. THP-1 cells expressing the above NLRP3 variants were sorted based upon Green Fluorescent Protein (GFP) expression. Cytokine response to alum (one of the most widely used adjuvants in vaccines) in the cells stably expressing NLRP3-WT and NLRP3-Q705K were determined. IL-1β and IL-18 levels were found to be elevated in THP-1 cells transduced with NLRP3-Q705K compared to the NLRP3-WT. Upon exposure to alum, THP-1 cells stably expressing NLRP3-Q705K displayed an increased production of IL-1β, IL-18 and TNF-α, in a caspase-1 and IL-1 receptor-dependent manner.

    Conclusions: Collectively, these findings show that the Q705K polymorphism in NLRP3 is a gain-of-function alteration leading to an overactive NLRP3 inflammasome. The option of IL-1β blockade may be considered in patients with chronic inflammatory disorders that are unresponsive to conventional treatments.

  • 118.
    Wang, C.
    et al.
    Uppsala University, Sweden .
    Ahlford, A.
    Uppsala University, Sweden .
    Laxman, N.
    Uppsala University, Sweden .
    Nordmark, G.
    Uppsala University, Sweden .
    Eloranta, M-L
    Uppsala University, Sweden .
    Gunnarsson, I.
    Karolinska Institute, Sweden .
    Svenungsson, E.
    Karolinska Institute, Sweden .
    Padyukov, L.
    Karolinska Institute, Sweden .
    Sturfelt, G.
    Lund University, Sweden .
    Jonsen, A.
    Lund University, Sweden .
    Bengtsson, A. A.
    Lund University, Sweden .
    Truedsson, L.
    Lund University, Sweden .
    Rantapaa-Dahlqvist, S.
    Umeå University, Sweden .
    Sjöwall, Christoffer
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Sandling, J. K.
    Uppsala University, Sweden Wellcome Trust Sanger Institute, England .
    Ronnblom, L.
    Uppsala University, Sweden .
    Syvanen, A-C
    Uppsala University, Sweden .
    Contribution of IKBKE and IFIH1 gene variants to SLE susceptibility2013Ingår i: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 14, nr 4, s. 217-222Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The type I interferon system genes IKBKE and IFIH1 are associated with the risk of systemic lupus erythematosus (SLE). To identify the sequence variants that are able to account for the disease association, we resequenced the genes IKBKE and IFIH1. Eighty-six single-nucleotide variants (SNVs) with potentially functional effect or differences in allele frequencies between patients and controls determined by sequencing were further genotyped in 1140 SLE patients and 2060 controls. In addition, 108 imputed sequence variants in IKBKE and IFIH1 were included in the association analysis. Ten IKBKE SNVs and three IFIH1 SNVs were associated with SLE. The SNVs rs1539241 and rs12142086 tagged two independent association signals in IKBKE, and the haplotype carrying their risk alleles showed an odds ratio of 1.68 (P-value = 1.0 x 10(-5)). The risk allele of rs12142086 affects the binding of splicing factor 1 in vitro and could thus influence its transcriptional regulatory function. Two independent association signals were also detected in IFIH1, which were tagged by a low-frequency SNV rs78456138 and a missense SNV rs3747517. Their joint effect is protective against SLE (odds ratio = 0.56; P-value = 6.6 x 10(-3)). In conclusion, we have identified new SLE-associated sequence variants in IKBKE and IFIH1, and proposed functional hypotheses for the association signals.

  • 119.
    Wang, Chuan
    et al.
    Uppsala University, Sweden.
    Ahlford, Annika
    Uppsala University, Sweden.
    Jarvinen, Tiina M.
    University of Helsinki, Finland.
    Nordmark, Gunnel
    Uppsala University, Sweden.
    Eloranta, Maija-Leena
    Uppsala University, Sweden.
    Gunnarsson, Iva
    Karolinska University Hospital, Sweden.
    Svenungsson, Elisabet
    Karolinska University Hospital, Sweden.
    Padyukov, Leonid
    Karolinska University Hospital, Sweden.
    Sturfelt, Gunnar
    Lund University, Sweden.
    Jonsen, Andreas
    Lund University, Sweden.
    Bengtsson, Anders A.
    Lund University, Sweden.
    Truedsson, Lennart
    Lund University, Sweden.
    Eriksson, Catharina
    University of Umeå Hospital, Sweden.
    Rantapaa-Dahlqvist, Solbritt
    Umeå University, Sweden.
    Sjöwall, Christoffer
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Julkunen, Heikki
    Peijas Hospital, Finland.
    Criswell, Lindsey A.
    University of Calif San Francisco, CA USA.
    Graham, Robert R.
    Genentech Inc, CA USA.
    Behrens, Timothy W.
    Genentech Inc, CA USA.
    Kere, Juha
    University of Helsinki, Finland.
    Ronnblom, Lars
    Uppsala University, Sweden.
    Syvanen, Ann-Christine
    Uppsala University, Sweden.
    Sandling, Johanna K.
    Uppsala University, Sweden.
    Genes identified in Asian SLE GWASs are also associated with SLE in Caucasian populations2013Ingår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 21, nr 9, s. 994-999Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent genome-wide association studies (GWASs) conducted in Asian populations have identified novel risk loci for systemic lupus erythematosus (SLE). Here, we genotyped 10 single-nucleotide polymorphisms (SNPs) in eight such loci and investigated their disease associations in three independent Caucasian SLE case–control cohorts recruited from Sweden, Finland and the United States. The disease associations of the SNPs in ETS1, IKZF1, LRRC18-WDFY4, RASGRP3, SLC15A4, TNIP1 and 16p11.2 were replicated, whereas no solid evidence of association was observed for the 7q11.23 locus in the Caucasian cohorts. SLC15A4 was significantly associated with renal involvement in SLE. The association of TNIP1 was more pronounced in SLE patients with renal and immunological disorder, which is corroborated by two previous studies in Asian cohorts. The effects of all the associated SNPs, either conferring risk for or being protective against SLE, were in the same direction in Caucasians and Asians. The magnitudes of the allelic effects for most of the SNPs were also comparable across different ethnic groups. On the contrary, remarkable differences in allele frequencies between Caucasian and Asian populations were observed for all associated SNPs. In conclusion, most of the novel SLE risk loci identified by GWASs in Asian populations were also associated with SLE in Caucasian populations. We observed both similarities and differences with respect to the effect sizes and risk allele frequencies across ethnicities.

  • 120.
    Wetterö, Jonas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Pettersson, Sofia
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi.
    Holmgren Peterson, Kajsa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    A cellular imaging CDIO project for 2nd semester students in engineering biology2006Ingår i: World Transactions on Engineering and Technology Education, ISSN 1446-2257, Vol. 5, nr 2, s. 279-282Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The demand for exact engineering within the life sciences is growing and the Engineering Biology programme at Linköping University, Linköping, Sweden, prepares students for a career at this interface. Conceive – Design – Implement – Operate (CDIO) was recently pioneered in an introductory project course. Groups of six to seven students apply a LIPS scalable project model from traditional engineering educational environments on, for example, a cellular imaging task in a hospital setting, prior to taking courses in cell biology/optics. Besides facilitating the implementation of CDIO in higher courses, students gain early career insight and enhance their communication skills. A customer (senior teacher) needs to visualise structures in cells, and the student group is contracted to deliver an applied and optimised method to meet specified requirements. The customer reviews deliverables before the tollgates and communicates with the student project leader. Other students are responsible for documentation and subsystems. The project is allocated laboratory facilities and hardware, and two fictitious subcontractors supply samples and consumables. Extra teachers perform supervision and methodological consultation. In summary, CDIO is indeed applicable and rewarding in cellular imaging, yet is also challenging.

  • 121.
    Wetterö, Jonas
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi.
    Hellerstedt, T.
    Nygren, Patrik
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik.
    Broo, K.
    Occupational and Environmental Medicine, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden.
    Aili, Daniel
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik.
    Liedberg, Bo
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik.
    Magnusson, Karl-Eric
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi.
    Immobilized chemoattractant peptides mediate adhesion and distinct calcium-dependent cell signaling in human neutrophils2008Ingår i: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 24, nr 13, s. 6803-6811Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chemotaxis is the stimulated directional migration of cells in response to chemotactic factors, manifested for instance during leukocyte interaction with chemoattractants in inflammation. The N-formyl-Met-Leu-Phe (fMLF) bacterial peptide family is particularly potent in attracting and activating neutrophilic granulocytes. To accomplish defined circumstances for recruitment and activation of cells, we fabricated semitransparent gold-coated glass coverslips functionalized with chemoattractant fMLF receptor peptide agonist analogues. Peptides based on a common leading four-amino-acid sequence Gly-Gly-Gly-Cys were thus coupled to two potent fMLF receptor agonists, N-formyl-Tyr-Nle-Phe-Leu- Nle-Gly-Gly-Gly-Cys and N-formyl-Met-Leu-Phe-Gly-Gly-Gly-Cys, and a formylated control peptide, N-formyl-Gly-Gly-Gly-Cys. They were anchored via the SH group of Cys either directly to the gold surface or a mixed self-assembled monolayer composed of maleimide- and hydroxyl-terminated oligo(ethylene glycol) alkyldisulfides. The overall peptide immobilization procedure was characterized with ellipsometry, contact angle measurement, and infrared spectroscopy. When exposed to granulocytes, the agonist surface rapidly recruited neutrophils and the cells responded with extensive spreading and intracellular calcium transients within minutes. The reference peptide generated no such activation, and the cells maintained a more spherical morphology, suggesting that we have been able to immobilize chemoattractant receptor agonist peptides with retained bioactivity. This is a crucial step in designing surfaces with specific effects on cellular behavior. © 2008 American Chemical Society.

  • 122.
    Wetterö, Jonas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Sjöwall, Christoffer
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Reduced serum levels of autoantibodies against monomeric C-reactive protein (CRP) in patients with acute coronary syndrome2009Ingår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 400, nr 1-2, s. 128-131Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Inflammation is pivotal in atherosclerosis. Minor C-reactive protein (CRP) response reflects low-grade vascular inflammation and the high-sensitivity CRP test with levels >= 3.0 mg/l predicts coronary vascular events and survival in angina pectoris as well as in healthy subjects. We and others recently reported autoantibodies against monomeric CRP (anti-CRP) in rheumatic conditions, e.g. systemic lupus erythematosus (SLE), and a connection between anti-CRP and cardiovascular disease in SLE has been suggested.

    Patients and methods: Anti-CRP serum levels were determined with ELISA in 140 individuals; 50 healthy controls and 90 patients with angiographically verified coronary artery disease of which 40 presented with acute coronary syndrome (ACS) and 50 with stable angina pectoris (SA).

    Results: Significantly lower anti-CRP levels were observed in ACS compared to SA and controls (p=0.019). ACS patients, who had not been prescribed statins before their respective cardiovascular event, had lower anti-CRP (p = 0.049). BMI correlated directly to anti-CRP levels in cross section analysis (p = 0.043), but there was no association between anti-CRP and smoking or cholesterol.

    Discussion: In ACS, it is plausible that ruptured plaques and inflamed tissue may be more prone to opsonization by monomeric CRP leading to consumption of anti-CRP, Hypothetically, surface-bound anti-CRP could thereby enhance the local inflammation in plaques.

  • 123.
    Ying, Fei
    et al.
    Affiliated Hospital, Guiyang Medical College.
    Chalise, Jaya Prakash
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Chenna Narendra, Sudeep
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Mattias
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Type I IFN protects against antigen-induced arthritis2011Ingår i: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 41, nr 6, s. 1687-1695Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autoimmune diseases including rheumatoid arthritis (RA) involve immune reactions against specific antigens. The type I IFN system is suspected to promote autoimmunity in systemic lupus erythematosus, but may also dampen immune reactions in e. g. inflammatory bowel disease. This prompted us to investigate the role of type I IFN in antigen-induced arthritis (AIA). The importance of type I IFN in methylated (m) BSA-induced arthritis was studied by using mice deficient for the type I IFN receptor (IFNAR) and by administration of the IFN-alpha activator viral double-stranded (ds) RNA or recombinant IFN-alpha at antigen sensitization. In IFNAR knock-out mice, arthritis severity was significantly higher than in WT mice. Administration of dsRNA at antigen sensitization protected WT but not IFNAR KO mice from arthritis. Also, addition of recombinant IFN-alpha during the immunization, but not the induction phase of arthritis, almost abolished arthritis. Protection mediated by IFN-alpha was accompanied by delayed and decreased antigen-specific proliferative responses, including impaired lymph node recall responses after intra-articular antigenic challenge. In conclusion, we demonstrate that type I IFN can prevent joint inflammation by downregulating antigen-specific cellular immunity.

  • 124.
    Zeffer, Elisabeth
    et al.
    Karolinska Institute.
    Salomonsson, Stina
    Karolinska Institute.
    Dzikaite, Vijole
    Karolinska Institute.
    Eliasson, Hakan
    Karolinska Institute.
    Ambrosi, Aurelie
    Karolinska Institute.
    Bergman, Gunnar
    Karolinska Institute.
    Fernlund, Eva
    Skane University Hospital.
    Theander, Elke
    Skane University Hospital.
    Ohman, Annika
    Uppsala University.
    Rydberg, Annika
    Umea University Hospital.
    Skogh, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Länskliniken för Reumatologi i Östergötland.
    Rantapaa-Dahlqvist, Solbritt
    Umea University Hospital.
    Elfving, Ase
    Karolinska Institute.
    Fored, Michael
    Karolinska Institute.
    Blomqvist, Paul
    Karolinska Institute.
    Ekbom, Anders
    Karolinska Institute.
    Lindstrom, Ulla
    Sahlgrens University Hospital.
    Melander, Mats
    Sahlgrens University Hospital.
    Winqvist, Ola
    Karolinska Institute.
    Sonesson, Sven-Erik
    Karolinska Institute.
    Gadler, Fredrik
    Karolinska Institute.
    Jonzon, Anders
    Uppsala University.
    Wahren-Herlenius, Marie
    Karolinska Institute.
    A Population-Based Investigation of the Autoantibody Profile in Mothers of Children with Atrioventricular Block in SCANDINAVIAN JOURNAL OF IMMUNOLOGY, vol 72, issue 3, pp 274-2752010Ingår i: SCANDINAVIAN JOURNAL OF IMMUNOLOGY, Blackwell Publishing Ltd , 2010, Vol. 72, nr 3, s. 274-275Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

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