Isotype distribution and clinical relevance of anti-β2-glycoprotein I (β2-GPI) antibodies: importance of IgA isotype

Abstract

The aim of this study was to evaluate the prevalence of IgG, IgA and IgM anti-beta2-GPI antibodies in anti-phospholipid syndrome (APS), and to establish the clinical significance of IgA type antibodies compared with the other isotypes. Anti-beta2-GPI antibodies were measured in the sera of 70 patients by solid-phase enzyme immunoassay in gamma-irradiated polystyrene plates coated with human purified beta2-GPI. Thirty-three out of the 70 patients were classified as having APS: three of them had primary, and 30 had secondary APS related to systemic lupus erythematosus (SLE). The remaining 37 patients had SLE without APS. Anti-beta2-GPI antibodies of IgG, IgA and IgM isotypes were present in 84.8%, 59.3% and 51.5% of patients with APS. Both the frequency and the level of each isotype were significantly higher in patients with APS. This association was very strong for IgA (P = 0.0004 for the antibody frequency and P < 0.0001 for the antibody level), as well as for IgG type antibodies (P < 0.0001 and P < 0.0001), whereas it was weaker for IgM (P = 0.01 and P = 0.04). A strong relationship was demonstrated between increased IgA anti-beta2-GPI antibody levels and a history of venous thrombosis, thrombocytopenia, heart valve disease, livedo reticularis and epilepsy. IgG anti-beta2-GPI antibodies were associated with the presence of lupus anticoagulant (LA) in addition to the main features of APS. However, antibodies of IgM isotype were related only to thrombocytopenia and heart valve disease. We recommend the evaluation of anti-beta2-GPI antibodies of IgA isotype in addition to IgG in patients with clinical suspicion of APS.

Differential assay reactivity of immunglobulin A anti-ß2 glycoprotein I antibodies: implications for the clinical interpretation of antiphospholipid antibody testing

“…In these patients, most of the pro-thrombotic antiphospholipid antibodies are directed to the lipid-binding plasma protein β 2 glycoprotein I (β 2 GPI) or to β 2 GPI/phospholipid complexes, rather than to phospholipids alone (3,4). The primary serological criteria to classify APS includes the demonstration of IgG or IgM β 2 GPI-dependent anti-cardiolipin (aCL) and/or IgG or IgM anti-β 2 GPI antibodies detected by solid-phase immunoassays (5).…”

IgA Antiphospholipid Antibodies and Anti-Domain 1 of Beta 2 Glycoprotein 1 Antibodies are Associated with Livedo Reticularis and Heart Valve Disease in Antiphospholipid Syndrome

“…Other non-criteria APS manifestations include livedo reticularis (LR), thrombocytopenia and heart valve disease (HVD) [3]. These manifestations can be observed in 20-30% of the APS patients [4,5].…”

“…The role of these antibodies in APS is, however, unclear. Lagos et al [3] found that LR, HVD, thrombocytopenia, and epilepsy are more common among subjects with increased IgA anti-β-2GPI antibodies. They also reported associations between increased IgA aCL antibodies and both LR and epilepsy [3].…”

The Prevalence and Clinical Significance of Iga Anti-Phosphatidylserine/ Prothrombin Antibodies in Systemic Autoimmune Diseases

“…IgA anti-β2GPI seem to be more prevalent in SLE patients as compared to IgA aCL (review in [8]). Therefore, IgA anti-β2GPI have gained clinical relevance and were recently included among the antiphospholipid antibodies tests in the novel SLICC classification criteria for SLE [15]. For that reason, in selected patients where clinical suspicion of APS is high (but all other antiphospholipid antibodies tests are negative) testing for IgA anti-β2GPI might be clinically useful and therefore recommended [16][17][18].…”