Seronegative antiphospholipid syndrome (SNAPS) is an autoimmune disease present in patients with clinical manifestations highly suggestive of Antiphospholipid Syndrome (APS) but with persistently negative consensus antiphospholipid antibodies (a-PL). IgA anti-β2 Glycoprotein I (aB2-GPI) antibodies are associated with APS. However, they are not currently considered to be laboratory criteria due to the heterogeneity of published works and the use of poor standardized diagnostic systems. We have aimed to assess aPL antibodies in a group of patients with clinical manifestations of APS (C-APS) to evaluate the importance of the presence of IgA aB2GPI antibodies in APS and its relation with other aPL antibodies. Only 14% of patients with C-APS were positive for any consensus antibody, whereas the presence of isolated IgA aB2GPI antibodies was found in 22% of C-APS patients. In patients with arterial thrombosis IgA aB2GPI, antibodies were the only aPL antibodies present. Serologic profile in primary APS (PAPS) is different from systemic autoimmune disorders associated APS (SAD-APS). IgA aB2GPI antibodies are more prevalent in PAPS and IgG aB2GPI antibodies are predominant in SAD-APS. The analysis of IgA aB2GPI antibodies in patients with clinical manifestations of PAPS might avoid underdiagnosed patients and provide a better diagnosis in patients with SAD-APS. Laboratory consensus criteria might consider including analysis of IgA aB2GPI for APS diagnosis.

BackgroundThe antiphospholipid syndrome (APS) is defined by simultaneous presence of vascular clinical events and antiphospholipid antibodies (aPL). The aPL considered as diagnostics are lupus anticoagulant and antibodies anticardiolipin (aCL) and anti-ß2 glycoprotein-I (aB2GP1). During recent years, IgA aB2GP1 antibodies have been associated with thrombotic events both in patients positive, and mainly negative for other aPL, however its value as a pro-thrombotic risk-factor in asymptomatic patients has not been well defined.ObjectiveTo test the role of IgA anti B2GP1 as a risk factor for the development of APS-events (thrombosis or pregnancy morbidity) in asymptomatic population with a 5-year follow-up.Methods244 patients isolated positive for anti-beta2-glycoprotein I IgA (Group-1 study) and 221 negative patients (Group-2 control) were studied. All the patients were negative for IgG and IgM aCL.ResultsDuring the follow-up, 45 patients (9.7%) had APS-events, 38 positive for IgA-aB2GP1 and 7 negative (15.6% vs 3.2%, p<0.001).The incidence rate of APS-events was 3.1% per year in IgA-aB2GP1 positive patients and 0.6% per year in the control group. Arterial thrombosis were the most frequent APS-events (N = 25, 55%) and were mainly observed in Group-1 patients (21 vs 4, p = 0.001). Multivariate analysis were shown as independent risk-factors for the development of APS-events, age, sex (men) and presence of IgA-aB2GP1 (odds ratio 5.25, 95% CI 2.24 to 12.32).ConclusionThe presence of IgA-aB2GP1 in people with no history of APS-events is the main independent risk factor for the development of these types of events, mainly arterial thrombosis.

IgA antibeta 2 Glycoprotein I (β2GPI) antibodies test can identify some patients with antiphospholipid syndrome (APS) that are negative for other isotypes. Controversy exists because some studies have reported a strong association of these antibodies with vascular disease, while others have not confirmed this observation. Our hypothesis is that these contradictory results may be due to differences among commercial diagnostic kits. To answer this question, we have compared the results obtained with several of the most commonly used commercial IgA anti β2GPI antibodies (aβ2GPI) diagnostic assays on specimens from individuals suspected of having APS. Sera from 69 patients (37 positive and 32 negative for IgA aβ2GPI) were analyzed with seven different commercial ELISA kits for IgA aβ2GPI, following instructions and cutoffs provided by the manufacturer. Our results showed important differences in the sensitivity and specificity of the different assays. Two of the seven kits tested had a sensitivity level below 65% for IgA aβ2GPI, and three showed levels of specificity lower than 80%. Some commercial kits to detect IgA aβ2GPI are suboptimal. Variability between kits may account for the discrepancy in results obtained and for the lack of consensus concerning their clinical significance. It is important that the scientific community work to standardize assay performance so that the true clinical significance of this important clinical marker can be clearly established.

In conclusion, pretransplant IgA-aB2GP1 was the main risk factor for graft thrombosis and early graft loss. Further research should be made on whether anticoagulation in antibody-positive patients could ameliorate this catastrophic complication.