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High anti-collagen type II antibody levels and induction of pro-inflammatory cytokines by anti-collagen antibody containing immune complexes in vitro characterize a distinct RA phenotype associated with acute inflammation at the time of disease onset
  1. Mohammed Mullazehi (mohammed.mullazehi{at}klinimm.uu.se)
  1. Unit of Clinical Immunology, Uppsala University, Uppsala, Sweden
    1. Linda Mathsson (linda.mathsson{at}klinimm.uu.se)
    1. Unit of Clinical Immunology, Uppsala University, Uppsala, Sweden
      1. Jon Lampa (jon.lampa{at}karolinska.se)
      1. Unit of Rheumatology, Karolinska Institute, Stockholm, Sweden
        1. Johan Rönnelid (johan.ronnelid{at}klinimm.uu.se)
        1. Unit of Clinical Immunology, Uppsala University, Uppsala, Sweden

          Abstract

          Objective: We have earlier reported cytokine- inducing properties of surface-bound collagen type II (CII)-containing immune complexes (IC). We have now investigated whether this finding might have clinical impact.

          Methods: Anti-CII serology was analyzed in 274 early RA patients. Patients with elevated levels of anti- CII were followed serially for 1-5 years concerning anti- CII IC-induced levels of TNF-a, IL-1ß and IL-8. Levels of antibodies and IC-induced cytokines were compared to clinical indices over five years of follow-up.

          Results: 5/100 healthy controls and 24/274 (8.8%) RA patients exhibited elevated levels (>29 AU/ml) of anti-native CII antibodies, a non-significant difference. 9/274 (3.3%) RA patients and no controls comprised a discrete group with very high anti-CII levels > 450 AU/ml. These very high anti-CII level sera were associated with induction of pro-inflammatory cytokines by anti-CII-containing IC formed in vitro. 8/9 patients with high baseline anti-CII levels exhibited a parallel decline in antibody levels, IC-induced cytokines, CRP and ESR. Anti-CII positive patients had significantly elevated levels of CRP and ESR at baseline but not later during the follow-up.

          Conclusions: Anti-native CII positive RA patients have a distinct clinical phenotype characterized by an early acute phase response that might be driven by anti- CII containing IC in joint cartilage.

          • antigen-antibody complex
          • collagen type II
          • cytokines
          • hyaline cartilage
          • rheumatoid arthritis

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