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

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 (a beta 2-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 (-) for aCL. Both groups were further classified according to disease severity. Patients were retested for both aCL and a beta 2-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%), a beta 2-GPI positive in 69/118 (58%) and 52/118 (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 a beta 2-GPI, and 75.7% were positive for one or both assays. When only one assay was positive, a beta 2-GPI was most frequent (P = 0.0096). Overall, IgA a beta 2-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 a beta 2-GPI positive, with 24/73 (32.9%) having isolated a beta 2-GPI. Of those positive for a beta 2-GPI, IgA a beta 2-GPI was present in 74.1%. Many of these patients had documented APS. Conclusion: Based on our data, a beta 2-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 a beta 2-GPI and aCL. IgA a beta 2-GPI appears to be the most important isotype detected.