title: Complement system and rheumatoid arthritis: relationships with autoantibodies, serological, clinical features, and anti-TNF treatment.
abstract: Autoantibodies (rheumatoid factor, RF; anti-citrullinated-protein antibodies, ACPA) and complement system are involved in rheumatoid arthritis (RA). ACPA and anti-TNF agents are capable of in vitro modulating complement activity. We investigated the relationships between complement, autoantibodies, and anti-TNF treatment in vivo. One-hundred fourteen RA patients (89F/25M), diagnosed according to 1987 ACR criteria, and 30 healthy controls were enrolled. Serological analysis included ESR, CRP, complement C3, C4 and CH50, RF and ACPA (ELISA, cut-off>20 U/ml). Split-products (SP) of C3 and B were studied by immunoelectrophoresis/counterimmunoelectrophoresis. Seventy-six patients started anti-TNF treatment and were studied at baseline and after 22 weeks. Disease activity was measured with DAS28 and response to therapy with EULAR criteria. At baseline, RA patients showed significantly higher levels of C3 and C4 than controls (C3 127.9±26.5 vs 110±25 mg/dl, P=0.0012; C4 29.7±10.2 vs 22.7±8.3mg/dl, P=0.0003). No differences in C3, C4 and CH50 levels were observed between ACPA+ (n=76) and ACPA- (n=38) patients. After 22 weeks of anti-TNF, C3, C4 and RF were significantly reduced (P<0.003, <0.005 and <0.04, respectively) and RF changes showed negative correlation with CH50. SP of C3 and B were observed neither at baseline nor after 22 weeks. DAS28 significantly improved after 22 weeks. Patients showing higher baseline C3 or lower reduction of C3 levels after 22 weeks had a worse EULAR outcome (X2=22.793, P<0.001). RF levels seem to correlate with complement CH50. The presence of high levels of C3 in RA patients may reflect a pro-inflammatory status and represent a negative prognostic factor for anti-TNF therapy.
authors.affiliation: Rheumatology, Allergology and Clinical Immunology, Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Di Muzio
authors.forename: C
authors.initials: C
authors.lastname: Perricone
authors.forename: E
authors.initials: E
authors.lastname: Ballanti
authors.forename: B
authors.initials: B
authors.lastname: Kroegler
authors.forename: E
authors.initials: E
authors.lastname: Greco
authors.forename: L
authors.initials: L
authors.lastname: Novelli
authors.forename: P
authors.initials: P
authors.lastname: Conigliaro
authors.forename: P
authors.initials: P
authors.lastname: Cipriani
authors.forename: R
authors.initials: R
authors.lastname: Giacomelli
authors.forename: R
authors.initials: R
authors.lastname: Perricone
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003176:Complement C3 / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism; D015941:Complement Hemolytic Activity Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007122:Immunoelectrophoresis; D007558:Italy; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011446:Prospective Studies; D012217:Rheumatoid Factor / Q000097:blood; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D015415:Biomarkers; D003176:Complement C3; D003181:Complement C4; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor