Complement System and Rheumatoid Arthritis: Relationships with Autoantibodies, Serological, Clinical Features, and Anti-TNF Treatment

Abstract

The first two authors contributed equally to this work 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>20U/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 1l0±25mgldl, P=O.0012; C4 29.7±10.2 vs 22.7±8.3mgldl, 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<O.OOI). 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.Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease affecting primarily the joints and resembling the features of autoimmunity. This complex multi-factorial disease affects approximately 0.5-1% of the population and leads to progressive joint destruction. Both environmental and genetic factors seem to be responsible for the susceptibility and phenotype (1).

Seroprevalence of Anti-Mannose Binding Lectin Autoantibodies in Patients With Rheumatoid Arthritis in Sana'a City- Yemen

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Recurrent Angioedema: Occurrence, Features, and Concomitant Diseases in an Italian Single-Center Study

“…Moreover, 62.5% of the aut-I-AAE patients had autoimmune thyroid disorders, representing a prevalence of 5.6% in the whole cohort. Clinical associations between urticarial/recurrent AE and autoimmune thyroid disease [24,46] , connective-tissue disorders, and systemic vasculitis are reported in the literature [47,48] . Defining a cause-effect relation between autoimmune disease and AE is still difficult.…”

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