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

• Published in: Lupus 2000-01, Vol.9 (1), p.33-41
• Main Authors: Greco, T P, Amos, M D, Conti-Kelly, A M, Naranjo, J D, Ijdo, J W
• Format: Article
• Language: English
• Subjects: Adult; Antibodies; Antibodies, Anticardiolipin - analysis; Anticoagulants; Anticoagulants - analysis; antiphospholipid syndrome; Antiphospholipid Syndrome - diagnosis; Antiphospholipid Syndrome - immunology; b2-glycoprotein I; beta 2-Glycoprotein I; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Glycoproteins - analysis; Humans; Immunoglobulin A - analysis; Immunoglobulin Isotypes - analysis; Laboratories; Lupus; Male; Middle Aged; Patients; Prospective Studies; Rheumatology
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/096120330000900107

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.