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High anti-collagen type-II antibody levels and induction of proinflammatory cytokines by anti-collagen antibody-containing immune complexes in vitro characterise a distinct rheumatoid arthritis phenotype associated with acute inflammation at the time of disease onset
  1. Mohammed Mullazehi1,
  2. Linda Mathsson1,
  3. Jon Lampa2,
  4. Johan Rönnelid1
  1. 1Unit of Clinical Immunology, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden
  2. 2Unit of Rheumatology, Department of Medicine, Karolinska Institute, Stockholm, Sweden
  1. Correspondence to:
    Dr J Rönnelid
    Unit of Clinical Immunology, Rudbeck Laboratory C5, SE-75185 Uppsala, Sweden; johan.ronnelid{at}klinimm.uu.se

Abstract

Objective: To investigate whether the cytokine-inducing properties of surface-bound collagen type II (CII)-containing immune complexes (IC), which were reported earlier, have any clinical impact.

Methods: Anti-CII serology was analysed in 274 patients with early rheumatoid arthritis (RA). Patients with increased levels of anti-CII were followed serially for 1–5 years with regard to anti-CII IC-induced levels of tumour necrosis factor (TNF)α, interleukin (IL)1β and IL8. Levels of antibodies and IC-induced cytokines were compared with clinical indices over 5 years of follow-up.

Results: 5/100 healthy controls and 24/274 (8.8%) patients with RA exhibited increased levels (>29 arbitrary units (AU)/ml) of anti-native CII antibodies, a non-significant difference. 9/274 (3.3%) patients with RA and no controls comprised a discrete group with high anti-CII levels >450 AU/ml. These 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, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Anti-CII-positive patients had significantly increased levels of CRP and ESR at baseline, but not later during the follow-up.

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

  • AU, arbitrary unit
  • BSA, bovine serum albumin
  • CII, collagen type II
  • CRP, C reactive protein
  • DAS, disease activity score
  • DMARD, disease-modifying antirheumatic drug
  • ESR, erythrocyte sedimentation rate
  • IC, immune complex
  • IL, interleukin
  • OD, optical density
  • PBMC, peripheral blood mononuclear cell
  • PBS, phosphate-buffered saline
  • RA, rheumatoid arthritis
  • RF, rheumatoid factor
  • TNF, tumour necrosis factor

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Footnotes

  • Published Online First 12 October 2006

  • Funding: The Swedish Fund for Research Without Animal Experiments and The Swedish Rheumatism Association.

  • Competing interests: None.

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