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SP0181 Failure of natural regulatory autoantibody network as cause of autoimunity
  1. OC Marques,
  2. on behalf of Lubeck University. Prof. Riemekasten
  1. Reumathology, University of Lübeck, 23562 Lübeck, Germany

Abstract

The role of autoantibodies in normal physiology is under debate. In investigating autoantibody (aab) concentrations against G protein-coupled receptors (GPCR) in different autoimmune diseases, we found both increased and decreased aab concentrations, which suggests physiological anti-GPCR aab levels may be dysregulated in autoimmune diseases. During our analysis of healthy donor antibodies to 16 GPCR and 15 growth factors and related signaling molecules, we discovered several clusters of correlations in these antibody concentrations. Possible functional interactions of these 31 autoantibody target molecules were studied by STRING, DAVID, and enriched Gene Ontology analyses. Through these analyses, a network of GPCR, growth factors, and signaling molecules with endothelin receptor type A (ETAR) in the center was revealed. Migration and locomotion were suggested to be the most significant functions regulated by the antibody network. Accordingly, IgG from healthy donors induced both IL-8 expression by peripheral blood mononuclear cells (PBMCs) as well as migration of neutrophils and tumor cells, which was specifically diminished by the ETAR inhibition. These data supports a change of paradigm from the notion that autoantibodies are an exclusive autoimmune phenomenon to the concept that they are part of the normal human physiology, which become dysregulated under the influence of different factors and subsequently cause autoimmune diseases.

Disclosure of Interest None declared

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