Moderator of 1 Session
Presenter of 2 Presentations
IS021 - ANTI-COLLAGEN TYPE II ANTIBODIES PROGNOSTICATE GOOD PROGNOSIS IN RHEUMATOID ARTHRITIS (ID 857)
Abstract
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Antibodies against the fibrillar cartilage collagen type II (anti-CII) can be detected in 6-9% of patients with rheumatoid arthritis (RA). Whereas rheumatoid factor and antibodies against citrullinated peptides/proteins (ACPA) can be detected many years before RA onset, anti-CII are absent during the years predating clinical disease, but seem to appear close to diagnosis in conjunction to clinical symtoms. We have described that in anti-CII positive patients, autoantibody levels are high at the time of diagnosis and thereafter decrease during the first year. We have developed an in vitro model to study the functional effects of surface-bound anti-CII-containing immune complexes (IC), mimicking how anti-CII can act when binding to CII exposed in hyaline cartilage in RA joints. Using that model, we have shown how anti-CII-containing IC induce the inflammatory cytokines TNF-α, IL-1β and IL-8 via FcγRIIa-mediated macrophage stimulation, and that granulocytes are especially important by co-stimulating macrophages to produce IL-8 and other chemokines via a mechanism dependent on TLR4 and the granulocyte enzymes elastase, cathepsin and myeloperoxidase. In agreement with these proinflammatory functions in vitro and declining anti-CII levels in vivo after RA diagnosis, anti-CII positive patients show an RA phenotype with acute onset with high levels of inflammatory markers but with good long-term prognosis This represents the opposite to ACPA-positive RA where the long-term prognosis is poor. Thus, analysis of anti-CII might be a means to define a group of newly diagnosed RA patients where special therapeutic considerations might be applicable. This hypothesis is currently investigated in large RA cohorts in an ongoing Scandinavian collaboration.
In this talk I will present our work on the functional role of anti-CII in vitro as well as our clinical studies in propectively followed RA cohorts.
IS029 - QUANTIFICATION OF AUTOANTIBODIES IN CIRCULATING IMMUNE COMPLEXES AS A PROGNOSTIC MARKER IN SLE (ID 878)
Abstract
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Published autoimmune serology research almost universally only concern free autoantibodies in body fluids, mostly in serum. In a number of autoimmune diseases, like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), disease-associated autoantibodies are known to form immune complexes (IC) in the circulation and/or in the target organs; in joints of RA patients and in e.g. in kidneys and skin of SLE patients. We regard “serum” as functionally constituting two separate compartments: free monomeric autoantibodies, and autoantibodies bound in immune complexes (IC), and hypothesise that the autoantibody fraction bound in IC is pathologically more relevant in a number of IC-associated autoimmune diseases. Following this hypothesis, it is logical to aim to evaluate autoantibody levels in the IC fraction in serum. But techniques to quantitate and to study the functional role of autoantibodies in IC is an unmet need, which our group explores. We have developed a technique to quantitate autoantibodies in the IC fraction in sera and other body fluids. The technique is based on magnetic beads with covalently coupled bioactive C1q. When the beads are mixed with body fluids, IgG/IgM-containing IC attach. Subsequently we elute and dissolve the bound IC, whereafter autoantibody content is measured in the eluates and results compared to serum levels and related to clinical phenotypes e.g. disease activity and treatment responses.
In the presentation I will present our work using this technique to study the role of IC-bound autoantibodies in SLE.