title: 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.
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)alpha, interleukin (IL)1beta 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.
authors.affiliation: Unit of Clinical Immunology, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Rudbeck Laboratory C5, SE-75185 Uppsala, Sweden.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Mullazehi
authors.forename: Linda
authors.initials: L
authors.lastname: Mathsson
authors.forename: Jon
authors.initials: J
authors.lastname: Lampa
authors.forename: Johan
authors.initials: J
authors.lastname: Rönnelid
mesh_terms: D000208:Acute Disease; D000936:Antigen-Antibody Complex / Q000276:immunology*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D053583:Interleukin-1beta / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000936:Antigen-Antibody Complex; D018501:Antirheumatic Agents; D001323:Autoantibodies; D015415:Biomarkers; D024043:Collagen Type II; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein