Testing for the antiphospholipid syndrome: importance of IgA anti-beta 2-glycoprotein I

Abstract

Background: Testing for the antiphospholipid syndrome (APS) using anticardiolipin antibodies (aCL) has been problematic. Titers may fluctuate or even become negative. Anti-beta 2 glycoprotein I assays (ab2-GPI) may be more reliable for diagnosis.Methods: In a prospective, blinded study over a nine-month period we retested all patients seen for routine follow-up visits in our clinic who had previously been evaluated for aCL-associated illnesses. Patients were stratified into two groups: group A—patients previously positive (/) for aCL; group B—patients previously negative (7) for aCL. Both groups were further classified according to disease severity. Patients were retested for both aCL and ab2-GPI (isotypes G, M, A for each) using uniform testing standards.Results: 118 patients with previously positive aCL (group A) were retested. Repeat aCL were positive in 52=118 (44%), ab2-GPI positive in 69=118 (58%) and 82=118 (69.5%) were positive for one or both assays. In patients with serious organ damage (92% with documented APS), 48.6% were aCL positive, 64% positive for ab2-GPI, and 75.7% were positive for one or both assays. When only one assay was positive, ab2-GPI was most frequent (P = 0.0096). Overall, IgA ab2-GPI was the most frequent isotype found (60.9%).On retesting of 73 aCL-negative patients (group B), 9=73 (12%) were aCL positive, 27=73 (36%) were ab2-GPI positive, with 24=73 (32.9%) having isolated ab2-GPI. Of those positive for ab2 GPI, IgA ab2-GPI was present in 74.1%. Many of these patients had documented APS.Conclusion: Based on our data, ab2-GPI assays are superior to aCL assays for diagnosis of APS. The combined use of both assays enhance positive testing results in up to 75% of patients with APS at any stage of illness. ACL negative patients suspected of having APS should be retested for both ab2-GPI and aCL. IgA ab2-GPI appears to be the most important isotype detected.