Complement activation in patients with primary antiphospholipid syndrome

• Published in: Annals of the rheumatic diseases Vol. 68; no. 6; pp. 1030 - 1035
• Main Authors: Oku, K, Atsumi, T, Bohgaki, M, Amengual, O, Kataoka, H, Horita, T, Yasuda, S, Koike, T
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2009; BMJ Publishing Group; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Anticoagulants; Antigen-Antibody Complex - analysis; Antiphospholipid Syndrome - blood; Antiphospholipid Syndrome - immunology; Biological and medical sciences; Blood Coagulation; Blood platelets; Case-Control Studies; Complement Activation - immunology; Complement C3 - analysis; Complement C3a - analysis; Complement C4 - analysis; Complement C4a - analysis; Connective Tissue Diseases - immunology; Cross-Sectional Studies; Disease; Diseases of the osteoarticular system; Female; Humans; Hypotheses; Immunoglobulins; Lupus; Male; Medical imaging; Medical sciences; Middle Aged; NMR; Nuclear magnetic resonance; Plasma; Pregnancy; Retrospective Studies; Statistics, Nonparametric; Thrombosis; Tumor Necrosis Factor-alpha - blood; Tumor necrosis factor-TNF; Young Adult; Vascular disease; Human; Immunopathology; Platelet; Antiphospholipid antibody syndrome; Rheumatology; Autoimmune disease; Cardiovascular disease; Hemopathy; Activation
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/ard.2008.090670

Objective:To investigate the significance of complement activation in patients with primary antiphospholipid syndrome (APS).Methods:Thirty-six patients with primary APS, 42 control patients with non-systemic lupus erythematosus (SLE) connective tissue diseases, and 36 healthy volunteers were analysed retrospectively. Serum complement levels (C3, C4, CH50) and anaphylatoxins (C3a, C4a, C5a) were examined in all subjects, and serum complement regulatory factors (factor H and factor I) were measured in patients with primary APS. Plasma anticoagulant activity was determined in a mixing test using the activated partial thromboplastin time.Results:Serum complement levels were significantly lower in patients with primary APS than in patients with non-SLE connective tissue diseases (mean (SD) C3: 81.07 (17.86) vs 109.80 (22.76) mg/dl, p<0.001; C4: 13.04 (8.49) vs 21.70 (6.96) mg/dl, p<0.001; CH50: 31.32 (8.76) vs 41.40 (7.70) U/ml, p<0.001) or healthy volunteers. Only two healthy subjects with low serum C4 levels showed hypocomplementaemia, whereas most patients with primary APS showed raised serum C3a and C4a. No subjects showed raised C5a. Patients with primary APS with low serum C3 or C4 had significantly higher levels of C3a or C4a than healthy controls. No patients had low serum complement regulatory factors. Among patients with primary APS, hypocomplementaemia was significantly more common in those with high anticoagulant activity than in those with low or normal activity.Conclusion:Hypocomplementaemia is common in patients with primary APS, reflecting complement activation and consumption, and was correlated with anticoagulant activity, suggesting that antiphospholipid antibodies may activate monocytes and macrophages via anaphylatoxins produced in complement activation.