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Four Anti-dsDNA Antibody Assays in Relation to Systemic Lupus Erythematosus Disease Specificity and Activity
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0002-2125-2931
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Linköping University, Faculty of Health Sciences.
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2015 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, no 5, 817-825 p.Article 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. Vol. 42, no 5, 817-825 p.
Keyword [en]
SYSTEMIC LUPUS ERYTHEMATOSUS; DOUBLE-STRANDED DNA; IMMUNOASSAY; AUTOANTIBODIES; INFLAMMATION; RHEUMATIC DISEASE
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-118866DOI: 10.3899/jrheum.140677ISI: 000353779400013PubMedID: 25684763OAI: oai:DiVA.org:liu-118866DiVA: diva2:817968
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: 2017-09-08
In thesis
1. Biomarkers and mediators in systemic lupus erythematosus: IFNα versus the CRP response, and evaluation of suPAR and anti-dsDNA antibody assays
Open this publication in new window or tab >>Biomarkers and mediators in systemic lupus erythematosus: IFNα versus the CRP response, and evaluation of suPAR and anti-dsDNA antibody assays
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which may affect multiple organ systems. Interferon alpha (IFNα) and autoantibodies that form immune complexes with nuclear antigens (ANA) are hallmarks believed to drive the disease into a vicious circle of inflammation, tissue damage, autoantigen exposure and autoantibody production.

In SLE, the disease course is characterized by episodes of exacerbations alternating with remissions. In order to best treat the patient it is important to closely monitor symptoms and signs of disease activity. Because of the disease heterogeneity, no single biomarker has yet been found to reflect SLE disease activity in general, although antidouble stranded DNA (anti-dsDNA) antibodies sometimes indicate activity, primarily with renal involvement, and constitutes an item of the SLE disease activity score SLEDAI-2K. However, the method of anti-dsDNA measurement is not standardized and therefore varies between different laboratories. In many other inflammatory conditions, such as rheumatoid arthritis and during bacterial infections, the C-reactive protein (CRP) level is a good indicator of ongoing inflammation, but in SLE and during viral infections, CRP commonly fails to reflect the degree of inflammation. Both viral infections and SLE are characterized by IFNα, and we thus aimed to elucidate whether IFNα can inhibit CRP production. Further, four assays for anti-dsDNA antibody measurements were evaluated with regard to SLE disease specificity and activity, and a new potential biomarker of inflammation, the soluble urokinase plasminogen activator receptor (suPAR), was assessed in relation to disease activity and organ damage.

An in vitro inhibitory effect of IFNα on CRP transcription and production was found in hepatocytes, and this was consolidated by in vivo studies of CRP and IFNα in sera from well-characterized SLE patients (KLURING; Kliniskt lupusregister i nordöstra Götaland). Here, CRP and disease activity were associated among patients without IFNα and without a CRP lowering gene variant (SNP rs1205). The poor disease activity compliance of CRP could therefore be explained, at least in part, by polymorphisms in the CRP gene and increased levels of IFNα. Critical differences between the methods measuring anti-dsDNA were found regarding disease specificity and ability to reflect disease activity and the results suggests the Crithidia luciliae immunofluorescence test (CLIFT) for diagnostic purposes and a bead-based multiplex assay (FIDIS) for monitoring of disease activity. Evaluation of suPAR in SLE revealed no association of suPAR with disease activity, but interestingly instead with accumulated organ damage. suPAR could therefore possibly be used to advert patients at high risk of organ damage.

A detailed biological and clinical characterization of established and emerging SLE biomarkers is of importance since it may improve the clinical management as well as increase the knowledge about disease mechanisms.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. 70 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1396
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-105505 (URN)10.3384/diss.diva-105505 (DOI)978-91-7519-393-9 (ISBN)
Public defence
2014-04-30, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
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Available from: 2014-03-25 Created: 2014-03-25 Last updated: 2017-09-08Bibliographically approved

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Enocsson, HelenaSjöwall, ChristofferWirestam, LinaDahle, CharlotteKastbom, AlfWetterö, JonasSkogh, Thomas
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