The prevalence and clinical associations of anticardiolipin antibodies in a large inception cohort of patients with connective tissue diseases.
OBJECTIVE
To determine the prevalence and clinical associations of anticardiolipin antibodies (aCL) in a blinded, controlled study of patients with a variety of connective tissue diseases (CTD) using a standardized aCL testing system.


METHODS
Anticardiolipin antibodies (IgG, IgM, and IgA) were measured by direct enzyme-linked immunosorbent assay (ELISA) in the baseline serum samples of patients enrolled in a Cooperative Study of Systematic Rheumatic Diseases (CSSRD), National Institutes of Health (NIH) supported, 5-year inception-cohort, prospective study of early rheumatic diseases: rheumatoid arthritis (RA, n = 70), systemic lupus erythematosus (SLE, n = 70), scleroderma (PSS, n = 45), myositis (PM/DM, n = 36), and early undifferentiated connective tissue disease (EUCTD, n = 165). Diagnosis was based on standardized criteria and determined at the last study visit. A nested group of patients with Sjögren's syndrome (SJ, n = 44) was also defined. Serum from 200 blood donors (BB) served as controls. Additional patients with known antiphospholipid syndrome (APS, n = 33) and ANCA-related renal vasculitis (ANCA, n = 52) were also studied. Laboratory personnel were blinded to sample diagnostic group.


RESULTS
The prevalence of either IgG or IgM aCL among each diagnostic group was RA 15.7%, SLE 15.76%, PSS 6.7%, PM/DM 8.3%, EUCTD 9.1%, SJ 6.8%, ANCA 3.8%, and BB controls 4.0%. Prevalence of aCL was significantly different for both the RA and SLE groups versus BB controls (P < 0.01) but not among other diagnostic groups. Only 2 study patients had positive tests for IgA aCL (1 with PM/DM and 1 with EUCTD) versus 15% of APS with positive IgA aCL. Study patients positive for IgG or IgM aCL were significantly more likely to have hemolytic anemia or a positive serologic test for syphilis and less likely to have Raynaud's phenomenon. However, no associations were found between aCL positivity and thrombocytopenia, seizures, renal insufficiency, presence of a positive antinuclear antibody or rheumatoid factor, subcutaneous nodules or digital ulcers.


CONCLUSIONS
Based on results from this large CSSRD inception cohort, anticardiolipin antibodies are present in approximately 16% of patients with RA or SLE but are less common in patients with PSS, PM/DM, EUCTD, SJ, and ANCA vasculitis, where their prevalence approaches that in the normal population. Few consistent clinical association can be found among patients with CTD who are aCL positive. The complete diagnostic and prognostic importance and specificity of these antibodies remains to be fully determined.
Merkel
P A
PA
Arthritis Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Chang
Y
Y
Pierangeli
S S
SS
Convery
K
K
Harris
E N
EN
Polisson
R P
RP
D017153:Antibodies, Anticardiolipin / Q000097:blood*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000276:immunology; D016022:Case-Control Studies; D015331:Cohort Studies; D003240:Connective Tissue Diseases / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D009220:Myositis / Q000276:immunology; D009316:National Institutes of Health (U.S.); D015995:Prevalence; D011446:Prospective Studies; D012109:Research Support as Topic; D012595:Scleroderma, Systemic / Q000276:immunology; D016037:Single-Blind Method; D012859:Sjogren's Syndrome / Q000276:immunology; D014481:United States; D014657:Vasculitis / Q000276:immunology
D017153:Antibodies, Anticardiolipin; D019268:Antibodies, Antineutrophil Cytoplasmic; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M