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¯uctuate 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 strati®ed into two groups: group AÐpatients previously positive () for aCL; group BÐpatients previously negative (7) for aCL. Both groups were further classi®ed 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 52a118 (44%), ab2-GPI positive in 69a118 (58%) and 82a118 (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), 9a73 (12%) were aCL positive, 27a73 (36%) were ab2-GPI positive, with 24a73 (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. Lupus (2000) 9, 33±41

IgA Anti-β2-Glycoprotein I Autoantibodies Are Associated with an Increased Risk of Thromboembolic Events in Patients with Systemic Lupus Erythematosus

“…While some studies have found an association between IgA aPL and the clinical manifestations of APS [1], [2], [6], [7], [9], [10], [12]–[17], others have reported no association [4], [5], [8], [11], [18]. Here, we have determined whether IgA aPL are associated with clinical manifestations using an approach that differs from previous studies.…”

Functional expression of IgA receptor FcαRI on human platelets

“…IgA anti-Ro/SSA, anti-La/SSB, anticardiolipin, and anti-␤ 2 -glycoprotein-I autoantibodies were found frequently in serum of patients with SLE and Sjogren's syndrome [55,56]. IgA anti-␤ 2 -glycoprotein-I autoantibodies, as the most important isotype in the antiphospholipid syndrome, were associated strongly with acute myocardial infarction and unexplained, recurrent abortions in women [57][58][59][60][61][62]. Furthermore, a significantly increased IgA rheumatoid factor (IgA-RF; IgA autoantibodies) was found in rheumatoid arthritis (RA) patients, and the appearance of IgA-RF is a good indicator for the development of RA [63].…”

FcαRI (CD89) Alleles Determine the Proinflammatory Potential of Serum IgA

“…Although the mean IgA1 and total IgA in samples from SLE patients are significantly higher than those from the normal population (50), IgA Abs have received little attention in SLE. IgA anti-Ro/SSA, anti-La/SSB, anti-cardiolipin, and anti-␤ 2 -glycoprotein-I autoantibodies are present in the serum of patients with SLE, Sjogren's syndrome, and anti-cardiolipin syndrome (45,51,52) and, very recently, reports indicate that not only EBV seropositivity but also a specific IgA Ab against EBV are associated with SLE patients (46,53). The reports of IgA autoantibodies and IgA anti-EBV seropositivity suggest a provocative and perhaps underappreciated link in which a more activating host response to IgA might influence an autoimmune and inflammatory response.…”