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Autoantibodies associated with RNA are more enriched than anti-dsDNA antibodies in circulating immune complexes in SLE
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Systemic Autoimmunity)
Unit of Rheumatology, Department of Medicine, Karolinska Institutet.
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2012 (English)In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 21, no 6, 586-595 p.Article in journal (Refereed) Published
Abstract [en]

To what extent different autoantibodies accumulate in systemic lupus erythematosus (SLE) immune complexes (ICs), and whether such accumulation is associated with disease activity has been investigated. ICs were isolated from SLE sera by both polyethylene glycol (PEG) precipitation and C1q-binding. Autoantibody specificities were determined using a lineblot assay quantified by densitometry. To compare the relative levels of autoantibodies, levels were normalized to the total levels of IgG measured by ELISA in sera and parallel ICs. Samples were investigated both in a cross-sectional design as well as in a paired design with samples obtained during both active and inactive SLE. All investigated autoantibody specificities except anti-dsDNA were enriched in circulating ICs as compared with parallel sera. The group of antibodies against RNA-associated antigens (anti-RNP/Sm, anti-Sm, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB/La) all exhibited higher median enrichment than the DNA-associated (anti-dsDNA, anti-histones, anti-nucleosomes) or cytoplasmic (anti-ribosomal P) antigens. In particular autoantibodies against RNP/Sm and SSA/Ro52 had the highest degree of enrichment in SLE PEG precipitates. These findings were corroborated by analysis of autoantibody content in C1q-bound ICs. There was no difference in degree of IC accumulation of the investigated autoantibodies during active and inactive SLE. Our findings demonstrate a difference in enrichment between autoantibodies against RNA- and DNA-associated autoantigens in isolated SLE IC, suggesting that the RNA-associated autoantibodies are more prone to form circulating ICs in SLE, in contrast to antibodies against DNA-associated autoantigens such as dsDNA. These finding have implications in understanding mechanisms of differential autoantibody accumulation in target organs in SLE.

Place, publisher, year, edition, pages
2012. Vol. 21, no 6, 586-595 p.
Keyword [en]
SLE, Immune complexes, anti-SSA, anti-SSB, Ro52, Ro60, anti-dsDNA, ANA
National Category
Rheumatology and Autoimmunity Immunology in the medical area
Research subject
Clinical Immunology
URN: urn:nbn:se:uu:diva-139527DOI: 10.1177/0961203311434938ISI: 000302915200002OAI: oai:DiVA.org:uu-139527DiVA: diva2:381557
Available from: 2010-12-28 Created: 2010-12-28 Last updated: 2012-05-22Bibliographically approved
In thesis
1. Functional Role of Immune Complexes in Rheumatic and Parasitic Diseases
Open this publication in new window or tab >>Functional Role of Immune Complexes in Rheumatic and Parasitic Diseases
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Immune complexes (IC) have key pathological roles in both autoimmune and infectious diseases. In this thesis functional mechanisms behind IC-driven inflammation in rheumatic diseases and tropical infections have been studied, with special focus on the contribution of autoantibodies and cytokine-inducing properties of IC. In the autoimmune disease SLE, increased levels of IC-induced cytokines were associated with both increased classical complement activation and the occurrence of the autoantibodies anti-SSA and anti-SSB, both directed against RNA-associated antigens. In addition, complement activation and anti-SSA synergistically predisposed to higher levels of IC in sera. In the following study it was demonstrated that also other autoantibodies against RNA-associated autoantigens were more enriched than anti-dsDNA in SLE IC.

Sudanese Visceral Leishmaniasis (VL) patients had elevated IC levels, and precipitated IC induced higher levels of GM-CSF, IL10, IL6 and IL1RA than control IC. Levels of IC were especially prominent in severely ill patients receiving antimony treatment, and a parallel association with IC induction of GM-CSF was demonstrated. Leishmania-infected patients were often rheumatoid factor (RF) positive and a substantial number displayed reactivity towards cyclic citrullinated peptide (CCP) antigens. Contrary to what was seen in Sudanese RA sera, the CCP reactivity was not restricted to citrulline but reacted equally well with arginine-containing control peptides. Levels of anti-CCP among VL patients were not due to cross-reactions with, or CCP-reactivity bound to IC.

I have demonstrated that IC are associated with the presence of autoantibodies in both SLE and in Leishmania infection. In SLE, autoantibodies against RNA-associated antigens were more prone to form circulating IC than anti-dsDNA. In Leishmania infection false reactivity against the CCP-autoantigen correlated to IC levels although the IC themselves did not contain such reactivity. In both diseases higher IC levels were associated with a more active disease, and purified IC induced key cytokines in disease pathogeneses.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 68 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 636
National Category
Immunology in the medical area
Research subject
Medical Science
urn:nbn:se:uu:diva-139529 (URN)978-91-554-7981-7 (ISBN)
Public defence
2011-02-17, Rudbecksalen, Dag Hammarskjölds väg 20, Uppsala, 09:15 (English)
Available from: 2011-01-27 Created: 2010-12-28 Last updated: 2011-03-11Bibliographically approved

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Mathsson, LindaEloranta, Maija-LeenaRönnblom, LarsRönnelid, Johan
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