High frequency of abnormal levels of IgA anti-beta2-glycoprotein I antibodies in patients with systemic lupus erythematosus: relationship with antiphospholipid syndrome.

OBJECTIVE: To determine the frequency of IgA, in addition to IgM and IgG, anti-beta2-GPI and anticardiolipin (aCL) antibodies in patients with systemic lupus erythematosus (SLE), and to relate the presence of these antibodies to symptoms of antiphospholipid antibody syndrome (APS).

METHODS: Sera from 100 blood bank donors (controls) and 48 patients with SLE were tested by ELISA. The same enzyme conjugates were used in the measurement of aCL and anti-beta2-GPI. Medical records were reviewed for the presence of manifestations of APS: arterial occlusion, pulmonary embolism, cerebrovascular accident, transient ischemic attack, venous thrombosis (deep or superficial), hemolytic anemia, thrombocytopenia, repeated fetal loss, leg ulcers, seizures, avascular bone necrosis, cerebritis, or migraine.

RESULTS: Above normal levels of antibodies of all 3 isotypes against beta2-GPI were found in 5% of controls and 73% of patients with SLE. Antibodies against cardiolipin in the 2 groups were found in 5 and 37%, respectively. IgA anti-beta2-GPI was found in 2% of controls and 58% of patients with SLE; in contrast, only 2% of patients with SLE had IgA aCL. In the 48 patients studied, thrombosis and fetal loss were present in 10 (Group 1), other manifestations of APS were present in 18 (Group 2), and none in 20 (Group 3). Antibodies to beta2-GPI of all 3 isotypes were found in a higher proportion of APS (Group 1 plus Group 2) (82%) than in Group 3 (50%) (p < 0.01, chi-squared). There was also a significantly higher proportion of patients with elevated anti-beta2-GPI in Group 1 (90%) than in Group 3 (p < 0.02). There was a significantly higher frequency (p < 0.01) and level (p < 0.05) of IgA anti-beta2-GPI in patients with APS than in those with no APS manifestations. Moreover, compared to aCL and with other isotypes of anti-beta2-GPI, the highest antibody levels were observed in IgA antibeta2-GPI.

CONCLUSION: The sensitivity of the anti-beta2-GPI antibody test for APS in patients with SLE is significantly increased by measuring IgA, in addition to IgM and IgG isotype.