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Wirestam, L., Enocsson, H., Skogh, T., Padyukov, L., Jonsen, A., Urowitz, M. B., . . . Sjöwall, C. (2019). Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort. Journal of Rheumatology, 46(5), 492-500
Open this publication in new window or tab >>Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort
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2019 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 46, no 5, p. 492-500Article in journal (Refereed) Published
Abstract [en]

Objective. In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes. Methods. We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age-and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively. Results. Compared to controls, baseline OPN was raised 4-fold in SLE cases (p amp;lt; 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI amp;gt;= 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p amp;lt; 0.0001), and patients with high disease activity (SLEDAI-2K amp;gt;= 5) had raised serum OPN (p amp;lt; 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p amp;lt; 0.0001) and impaired estimated glomerular filtration rate (p = 0.01). Conclusion. The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.

Place, publisher, year, edition, pages
J RHEUMATOL PUBL CO, 2019
Keywords
SYSTEMIC LUPUS ERYTHEMATOSUS; BIOMARKERS; OSTEOPONTIN; DISEASE ACTIVITY; ORGAN DAMAGE; PROGNOSIS
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-156906 (URN)10.3899/jrheum.180713 (DOI)000466402600010 ()30647177 (PubMedID)
Note

Funding Agencies|Swedish Rheumatism Association; County Council of Ostergotland; Swedish Society of Medicine; King Gustaf V and Queen Victorias Freemasons foundation; King Gustaf Vs 80-year anniversary foundation; Hanyang University [201600000001387]; Lupus UK; NIHR/Wellcome Trust Clinical Research Facility; US National Institutes of Health (NIH) [AR43727]; Singer Family Fund for Lupus Research; Arthritis Research UK; NIHR Manchester Biomedical Research Centre; NIHR/Wellcome Trust Clinical Research Facility at Manchester University National Health Service (NHS) Foundation Trust; Danish Rheumatism Association [A1028]; NIH [RR00046]

Available from: 2019-05-28 Created: 2019-05-28 Last updated: 2019-06-18
Olsson, L. M., Johansson, Å. C., Gullstrand, B., Jönsen, A., Saevarsdottir, S., Rönnblom, L., . . . Holmdahl, R. (2017). A single nucleotide polymorphism in the NCF1 gene leading to reduced oxidative burst is associated with systemic lupus erythematosus. Annals of the Rheumatic Diseases, 76(9), 1607-1613
Open this publication in new window or tab >>A single nucleotide polymorphism in the NCF1 gene leading to reduced oxidative burst is associated with systemic lupus erythematosus
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2017 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, no 9, p. 1607-1613Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Ncf1 polymorphisms leading to low production of reactive oxygen species (ROS) are strongly associated with autoimmune diseases in animal models. The human NCF1 gene is very complex with both functional and non-functional gene copies and genotyping requires assays specific for functional NCF1 genes. We aimed at investigating association and function of the missense single nucleotide polymorphism (SNP), rs201802880 (here denoted NCF1-339) in NCF1 with systemic lupus erythematosus (SLE).

METHODS: We genotyped the NCF1-339 SNP in 973 Swedish patients with SLE and 1301 controls, using nested PCR and pyrosequencing. ROS production and gene expression of type 1 interferon-regulated genes were measured in isolated cells from subjects with different NCF1-339 genotypes.

RESULTS: We found an increased frequency of the NCF1-339 T allele in patients with SLE, 11% compared with 4% in controls, OR 3.0, 95% CI 2.4 to 3.9, p=7.0×10(-20). The NCF1-339 T allele reduced extracellular ROS production in neutrophils (p=0.004) and led to an increase expression of type 1 interferon-regulated genes. In addition, the NCF1-339 T allele was associated with a younger age at diagnosis of SLE; mean age 30.3 compared with 35.9, p=2.0×1(-6).

CONCLUSIONS: These results clearly demonstrate that a genetically controlled reduced production of ROS increases the risk of developing SLE and confirm the hypothesis that ROS regulate chronic autoimmune inflammatory diseases.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2017
Keywords
NADPH oxidase complex, NCF1, SLE, autoimmunity, reactive oxygen species
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-139139 (URN)10.1136/annrheumdis-2017-211287 (DOI)000407833100033 ()28606963 (PubMedID)2-s2.0-85024929994 (Scopus ID)
Note

Funding agencies: Knut and Alice Wallenberg Foundation; Swedish Rheumatism Association; Swedish Medical Research Council; Swedish Research Council; Swedish Foundation for Strategic Research; King Gustaf Vs 80-Year Fund; Alfred Osterlund, Greta and Johan Kock, Anna-Greta Cr

Available from: 2017-07-03 Created: 2017-07-03 Last updated: 2018-05-03Bibliographically approved
Wirestam, L., Frodlund, M., Enocsson, H., Skogh, T., Wetterö, J. & Sjöwall, C. (2017). Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE. Lupus Science and Medicine, 4(1), Article ID 000225.
Open this publication in new window or tab >>Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE
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2017 (English)In: Lupus Science and Medicine, ISSN 2053-8790, E-ISSN 1625-9823, Vol. 4, no 1, p. 7article id 000225Article in journal (Refereed) Published
Abstract [en]

Objective The variety of disease phenotypes among patients with SLE challenges the identification of new biomarkers reflecting disease activity and/or organ damage. Osteopontin (OPN) is an extracellular matrix protein with immunomodulating properties. Although raised levels have been reported, the pathogenic implications and clinical utility of OPN as a biomarker in SLE are far from clear. Thus, the aim of this study was to characterise OPN in SLE.

Methods Sera from 240 well-characterised adult SLE cases classified according to the American College of Rheumatology (ACR) and/or the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and 240 population-based controls were immunoassayed for OPN. The SLE Disease Activity Index 2000 (SLEDAI-2K) was used to evaluate disease activity and the SLICC/ACR Damage Index (SDI) to detect damage accrual.

Results Serum OPN levels were in average raised fourfold in SLE cases compared with the controls (p<0.0001). OPN correlated with SLEDAI-2K, especially in patients with a disease duration of <12 months (r=0.666, p=0.028). OPN was highly associated with SDI (p<0.0001), especially in the renal (p<0.0001), cardiovascular (p<0.0001) and malignancy (p=0.012) domains. Finally, OPN associated with coherent antiphospholipid syndrome (APS; p=0.009), and both clinical and laboratory criteria of APS had significant positive impact on OPN levels.

Conclusions In this cross-sectional study, circulating OPN correlates with disease activity in recent-onset SLE, reflects global organ damage and associates with APS. Longitudinal studies to dissect whether serum OPN also precedes and predicts future organ damage are most warranted.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2017. p. 7
National Category
Rheumatology and Autoimmunity Neurology Clinical Laboratory Medicine Cardiac and Cardiovascular Systems Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-140711 (URN)10.1136/lupus-2017-000225 (DOI)
Available from: 2017-09-08 Created: 2017-09-08 Last updated: 2017-09-08Bibliographically approved
Wirestam, L., Schierbeck, H., Skogh, T., Gunnarsson, I., Ottosson, L., Erlandsson-Harris, H., . . . Sjöwall, C. (2015). Antibodies against High Mobility Group Box protein-1 (HMGB1) versus other anti-nuclear antibody fine-specificities and disease activity in systemic lupus erythematosus. Arthritis Research & Therapy, 17(338)
Open this publication in new window or tab >>Antibodies against High Mobility Group Box protein-1 (HMGB1) versus other anti-nuclear antibody fine-specificities and disease activity in systemic lupus erythematosus
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2015 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 17, no 338Article in journal (Refereed) Published
Abstract [en]

Introduction: The non-histone nuclear protein high mobility group box protein-1 (HMGB1) is typically associated with nucleosomes, but may shuttle between the nucleus and the cytoplasm, and under some conditions also be released extracellularly and participate in systemic inflammation. Monoclonal HMGB1-targeting antibodies can ameliorate murine polyarthritis and lupus-like disease. Interestingly, autoantibodies against HMGB1 have also been described in patients with systemic lupus erythematosus (SLE), but their clinical implications remain elusive. The main aims of this study were to detect serum anti-HMGB1 antibodies in patients with SLE and relate them to other types of antinuclear antibodies (ANA), and to disease activity. Methods: 188 Swedish SLE patients meeting the 1982 American College of Rheumatology classification criteria and/or the 2012 Systemic Lupus International Collaborating Clinics classification criteria participated in the study. Anti-HMGB1 antibody levels were analysed in patient and control (n = 112) sera by an in-house ELISA using recombinant histidine-tagged HMGB1. SLE sera were also analysed for ANA by immunofluorescence (IF) microscopy (IF-ANA) using fixed HEp-2 cells, and by a line-blot assay for antigen fine-specificities. To quantify antibodies to double-stranded DNA, a fluoroenzyme-immunoassay was employed. Results: At inclusion, 23 % of the SLE patients were anti-HMGB1 antibody positive compared to 5 % of the controls. Anti-HMGB1 antibodies occurred in 49 % of the IF-ANA positive SLE patients, and in 34 % of IF-ANA negative cases (p = 0.004). Levels of anti-HMGB1 antibodies correlated with anti-dsDNA antibody levels (r = 0.49; p less than 0.001). Significant, but less pronounced correlations were found regarding anti-HMGB1 and SLE disease activity index (SLEDAI-2K: r = 0.15; p = 0.04), classical complement function (r = -0.24; p = 0.002) and complement protein C4 (r = -0.23; p = 0.002). Average anti-HMGB1 antibody levels were significantly higher among patients with homogenous +/- other IF-ANA staining patterns (median 180 AU) compared to IF-ANA negative cases (median 83 AU) (p = 0.004). Rabbit anti-HMGB1 antibodies gave rise to cytoplasmic, but not nuclear, staining of HEp-2 cells. Conclusions: We confirm that anti-HMGB1 antibodies are common in SLE and correlate with disease activity variables. Although anti-HMGB1 antibodies measured by ELISA often coincide with nuclear IF-ANA staining, our results indicate that anti-HMGB1 antibodies do not give rise to nuclear staining of the predominantly used commercial HEp-2 cell slides.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2015
Keywords
HMGB1; Autoantibodies; SLE; Antinuclear antibodies; Inflammation; Clinical phenotype; Complement proteins
National Category
Basic Medicine
Identifiers
urn:nbn:se:liu:diva-123521 (URN)10.1186/s13075-015-0856-2 (DOI)000365252900001 ()26596890 (PubMedID)
Note

Funding Agencies|Swedish Society for Medical Research, Region Ostergotland; Swedish Research Council; Swedish Rheumatism Association; Swedish Society of Medicine; Professor Nanna Svartz foundation; King Gustaf Vs 80-year foundation

Available from: 2015-12-22 Created: 2015-12-21 Last updated: 2018-01-10
Enocsson, H., Sjöwall, C., Wirestam, L., Dahle, C., Kastbom, A., Ronnelid, J., . . . Skogh, T. (2015). Four Anti-dsDNA Antibody Assays in Relation to Systemic Lupus Erythematosus Disease Specificity and Activity. Journal of Rheumatology, 42(5), 817-825
Open this publication in new window or tab >>Four Anti-dsDNA Antibody Assays in Relation to Systemic Lupus Erythematosus Disease Specificity and Activity
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2015 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, no 5, p. 817-825Article in journal (Refereed) Published
Abstract [en]

Objective. Analysis of antibodies against dsDNA is an important diagnostic tool for systemic lupus erythematosus (SLE), and changes in anti-dsDNA antibody levels are also used to assess disease activity. Herein, 4 assays were compared with regard to SLE specificity, sensitivity, and association with disease activity variables. Methods. Cross-sectional sera from 178 patients with SLE, of which 11 were followed consecutively, from a regional Swedish SLE register were analyzed for immunoglobulin G (IgG) anti-dsDNA by bead-based multiplex assay (FIDIS; Theradig), fluoroenzyme-immunoassay (EliA; Phadia/Thermo Fisher Scientific), Crithidia luciliae immunofluorescence test (CLIFT; ImmunoConcepts), and line blot (EUROLINE; Euroimmun). All patients with SLE fulfilled the 1982 American College of Rheumatology and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) classification criteria. Healthy individuals (n = 100), patients with rheumatoid arthritis (n = 95), and patients with primary Sjogren syndrome (n = 54) served as controls. Results. CLIFT had the highest SLE specificity (98%) whereas EliA had the highest sensitivity (35%). When cutoff levels for FIDIS, EliA, and EUROLINE were adjusted according to SLICC-12 (i.e., double the reference limit when using ELISA), the specificity and sensitivity of FIDIS was comparable to CLIFT. FIDIS and CLIFT also showed the highest concordance (84%). FIDIS performed best regarding association with disease activity in cross-sectional and consecutive samples. Fishers exact test revealed striking differences between methods regarding associations with certain disease phenotypes. Conclusion. CLIFT remains a good choice for diagnostic purposes, but FIDIS performs equally well when the cutoff is adjusted according to SLICC-12. Based on results from cross-sectional and consecutive analyses, FIDIS can also be recommended to monitor disease activity.

Place, publisher, year, edition, pages
Journal of Rheumatology, 2015
Keywords
SYSTEMIC LUPUS ERYTHEMATOSUS; DOUBLE-STRANDED DNA; IMMUNOASSAY; AUTOANTIBODIES; INFLAMMATION; RHEUMATIC DISEASE
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-118866 (URN)10.3899/jrheum.140677 (DOI)000353779400013 ()25684763 (PubMedID)
Note

Funding Agencies|Swedish Research Council [K2012-69X-14594-10-3, K2011-68X-20611-04-3]; Swedish Society for Medicine [SLS-331171]; Swedish Society Against Rheumatism [R-313701, R-307291]; Swedish Society for Medical Research; King Gustaf V 80-year Foundation [FAI2013-0066]; Professor Nanna Svartz foundation

Available from: 2015-06-08 Created: 2015-06-04 Last updated: 2018-11-07
Björk, M., Dahlström, Ö., Wetterö, J. & Sjöwall, C. (2015). Quality of life and acquired organ damage are intimately related to activity limitations in patients with systemic lupus erythematosus. BMC Musculoskeletal Disorders, 16(188)
Open this publication in new window or tab >>Quality of life and acquired organ damage are intimately related to activity limitations in patients with systemic lupus erythematosus
2015 (English)In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 16, no 188Article in journal (Refereed) Published
Abstract [en]

Background: Systemic lupus erythematosus (SLE) is an autoimmune multi-organ disease, characterized by episodes of disease flares and remissions over time, which may restrain affected patients ability to perform daily activities. The purpose of the present study was to characterize variation in activity limitations among well-defined SLE patients, and to describe disease phenotypes, acquired organ damage and their relations to activity limitation and self-reported health, respectively. Methods: The disease phenotypes were organized into 4 different clinical groups and logistic regression analyses were used to identify how an elevated health assessment questionnaire (HAQ) score was related to disease variables such as phenotypes, disease activity and damage accrual. Correlation and multiple linear regression analyses were used to examine the association between each group of variables - background variables, disease variables and self-reported measurements - and the degree of elevated HAQ. Results: We found a higher proportion of activity limitation in patients with skin and joint involvement compared to others. The presence of activity limitation, as detected by the HAQ instrument, was significantly associated with quality of life (EuroQol-5D) and accrual of organ damage using the Systemic Lupus International Collaborative Clinics/ACR damage index. Conclusions: The findings highlight the differing requirements of the multi-professional rehabilitation interventions for the various SLE phenotypes in order to optimize the clinical care of the patients.

Place, publisher, year, edition, pages
BioMed Central / Springer Verlag (Germany), 2015
Keywords
Systemic lupus erythematosus; Disease burden; Organ damage; Disability; Quality of life; Activity limitation; Disease phenotype
National Category
Basic Medicine
Identifiers
urn:nbn:se:liu:diva-120858 (URN)10.1186/s12891-015-0621-3 (DOI)000359281700001 ()26264937 (PubMedID)
Note

Funding Agencies|County Council of Ostergotland; Swedish Society for Medical Research; Swedish Rheumatism Association; Swedish Society of Medicine; Professor Nanna Svartz foundation; King Gustaf V 80-year foundation; research foundation in memory of Clas Groschinsky; research foundation in memory of apotekare Hedberg

Available from: 2015-08-28 Created: 2015-08-28 Last updated: 2018-04-07
Enocsson, H., Sjöwall, C. & Wetterö, J. (2015). Soluble urokinase plasminogen activator receptor: A valuable biomarker in systemic lupus erythematosus?. Clinica Chimica Acta, 444, 234-241
Open this publication in new window or tab >>Soluble urokinase plasminogen activator receptor: A valuable biomarker in systemic lupus erythematosus?
2015 (English)In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 444, p. 234-241Article, review/survey (Refereed) Published
Abstract [en]

Systemic lupus erythematosus (SLE) is a potentially severe autoimmune condition with an unpredictable disease course, often with fluctuations in disease activity over time. Long term inflammation and drug-related side-effects may subsequently lead to permanent organ damage, a consequence which is intimately connected to decreased quality of life and mortality. New lupus biomarkers that convey information regarding inflammation and/or organ damage are thus warranted. Today, there is no clinical biomarker that indicates the risk of damage accrual. Herein we highlight the urokinase plasminogen activator receptor (uPAR) and especially its soluble form (suPAR) that besides having biological functions in e.g. proteolysis, cell migration and tissue homeostasis, recently has emerged as a promising biomarker of inflammation and prognosis of several disorders. A strong association between suPAR and organ damage in SLE was recently demonstrated, and preliminary data (presented in this review) suggests the possibility of a predictive value of suPAR blood levels. The involvement of suPAR in the pathogenesis of SLE remains obscure, but its effects in leukocyte recruitment, phagocytic uptake of dying cells (efferocytosis) and complement regulation suggests that the central parts of the SLE pathogenesis could be regulated by suPAR, and vice versa.

National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-115149 (URN)10.1016/j.cca.2015.02.031 (DOI)000353007500041 ()25704300 (PubMedID)
Available from: 2015-03-10 Created: 2015-03-10 Last updated: 2017-12-04
Enocsson, H., Sjöwall, C., Kastbom, A., Skogh, T., Eloranta, M.-L., Rönnblom, L. & Wetterö, J. (2014). Association of Serum C-Reactive Protein Levels With Lupus Disease Activity in the Absence of Measurable Interferon-α and a C-Reactive Protein Gene Variant. Arthritis & rheumatology (Hoboken, N.J.), 66(6), 1568-1573
Open this publication in new window or tab >>Association of Serum C-Reactive Protein Levels With Lupus Disease Activity in the Absence of Measurable Interferon-α and a C-Reactive Protein Gene Variant
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2014 (English)In: Arthritis & rheumatology (Hoboken, N.J.), ISSN 2326-5191, Vol. 66, no 6, p. 1568-1573Article in journal (Refereed) Published
Abstract [en]

Objectives: The type I interferon (IFN) system is important in the pathogenesis of systemic lupus erythematosus (SLE). We previously demonstrated an inhibitory effect of IFNα on interleukin 6 (IL-6) induced C-reactive protein (CRP) in vitro, hypothetically explaining the poor correlation between disease activity and CRP levels in SLE. Herein we investigated disease activity, IL-6 and CRP in relation to a CRP gene polymorphism and IFN.

Methods: Sera from 155 SLE patients and 100 controls were analyzed for CRP. Patients were genotyped for a CRP single nucleotide polymorphism (rs1205) associated with low CRP levels. Serum IFNα and IL-6 was quantified by immunoassays. Clinical disease activity was assessed by SLE disease activity index 2000 (SLEDAI-2K).

Results: CRP levels were increased in SLE patients compared to controls, but were not associated with SLEDAI-2K or IL-6 levels. However, exclusion of patients carrying at least one rs1205 minor allele revealed an association between disease activity and CRP levels (p=0.005). We found a strong association between disease activity and CRP levels (p<0.0005) when patients with measurable IFNα as well as the minor allele of rs1205 where excluded from the analysis. Similarly, when patients with raised IFNα and/or the rs1205 polymorphism were excluded, IL-6 associated with CRP levels.

Conclusions: The present study demonstrates that serum IFNα as well as CRP genotype affects the CRP response in SLE patients. Lack of correlation between serum levels of CRP and disease activity could therefore be explained by activation of the type I IFN system and polymorphisms in the CRP gene. © 2014 American College of Rheumatology.

Place, publisher, year, edition, pages
Hoboken, NJ, United States: John Wiley & Sons, 2014
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-105501 (URN)10.1002/art.38408 (DOI)000337366200018 ()24574329 (PubMedID)
Available from: 2014-03-25 Created: 2014-03-25 Last updated: 2015-08-31Bibliographically approved
Sjöwall, C., Olin, A. I., Skogh, T., Wetterö, J., Mörgelin, M., Nived, O., . . . Bengtsson, A. A. (2013). C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis. Autoimmunity, 46(3), 205-214
Open this publication in new window or tab >>C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis
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2013 (English)In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 46, no 3, p. 205-214Article in journal (Refereed) Published
Abstract [en]

The pattern recognition molecules C-reactive protein (CRP) and C1q are of big interest in relation to the pathogenesis of systemic lupus erythematosus (SLE). Circulating autoantibodies against CRP and C1q are frequently found in SLE patients with active disease, particularly in lupus nephritis (LN), and rising levels reportedly relate to disease activity and outcome. If CRP-, or dsDNA- and/or C1q-containing immune complexes (ICs) are pathogenic in LN, glomerular IgG-deposits would be expected to co-localize with these antigens. In search for proof of this concept, renal biospsies from patients with active LN (n=5) were examined with high-resolution immunogold electron microscopy. Renal biopsies from patients with Henoch-Schönlein purpura, pauci-immune nephritis and renal cancer served as controls. IgG antibodies against CRP, C1q and nucleosomes were analyzed in pre–post flare sera. We could demonstrate that CRP, C1q, C3c and dsDNA were co-localized with IgG in electron dense deposits in the glomerular basement membrane/subendothelial space in all of the 5 LN patients. Deposits of IgG, CRP, complement and dsDNA were 10-fold higher in LN compared to controls. All SLE patients had circulating anti-nucleosome antibodies; 4/5 had serum antibodies against CRP, dsDNA, and C1q at biopsy/flare. Despite a limited number of cases, the results support the notion of a pathogenic role not only for anti-dsDNA antibodies, but also for anti-CRP and anti-C1q in LN. The glomerular ICs may have been generated by deposition of circulating ICs or by in situ IC formation.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
Keywords
C-reactive protein; C1q; autoantibody; immune complex; lupus nephritis; systemic lupus erythematosus; immunogold electron microscopy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-96152 (URN)10.3109/08916934.2013.764992 (DOI)000317491300003 ()
Available from: 2013-08-14 Created: 2013-08-14 Last updated: 2017-12-06Bibliographically approved
Enocsson, H., Wetterö, J., Skogh, T. & Sjöwall, C. (2013). Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus. Translational Research: The Journal of Laboratory and Clinical Medicine, 162(5), 287-296
Open this publication in new window or tab >>Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus
2013 (English)In: Translational Research: The Journal of Laboratory and Clinical Medicine, ISSN 1931-5244, E-ISSN 1878-1810, Vol. 162, no 5, p. 287-296Article in journal (Refereed) Published
Abstract [en]

Assessments of disease activity and organ damage in systemic lupus erythematosus (SLE) remain challenging because of the lack of reliable biomarkers and disease heterogeneity. Ongoing inflammation can be difficult to distinguish from permanent organ damage caused by previous flare-ups or medication side effects. Circulating soluble urokinase plasminogen activator receptor (suPAR) has emerged as a potential marker of inflammation and disease severity, and an outcome predictor in several disparate conditions. This study was done to evaluate suPAR as a marker of disease activity and organ damage in SLE. Sera from 100 healthy donors- and 198 patients with SLE fulfilling the 1982 American College of Rheumatology classification criteria and/or the Fries criteria were analyzed for suPAR by enzyme immunoassay. Eighteen patients with varying degree of disease activity were monitored longitudinally. Disease activity was assessed by the SLE disease activity index 2000 and the physicians global assessment. Organ damage was evaluated by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). Compared with healthy control subjects, serum suPAR levels were elevated significantly in patients with SLE. No association was recorded regarding suPAR levels and SLE disease activity in cross-sectional or consecutive samples. However, a strong association was observed between suPAR and SDI (P andlt; 0.0005). Considering distinct SDI domains, renal, neuropsychiatric, ocular, skin, and peripheral vascular damage had.a significant effect on suPAR levels. This study is the first to demonstrate an association between serum suPAR and irreversible organ damage in SLE. Further studies are warranted to evaluate suPAR and other biomarkers as predictors of evolving organ damage.

Place, publisher, year, edition, pages
Elsevier, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-101384 (URN)10.1016/j.trsl.2013.07.003 (DOI)000326255600003 ()
Note

Funding Agencies|Swedish Research Council|K2012-69X-14594-10-3|County Council of Ostergotland||Swedish Society of Medicine||Swedish Society for Medical Research||Swedish Rheumatism Association||King Gustaf V 80-Year, Clas Groschinsky, Ingrid Svensson, Bror Karlsson, Gunnar Trosell, Magn. Bergvall, Sigurd Elsa Golje||Nanna Svartz research foundations||

Available from: 2013-11-22 Created: 2013-11-21 Last updated: 2017-12-06
Organisations
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ORCID iD: ORCID iD iconorcid.org/0000-0002-6916-5490

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