The presence of IgG antibodies against β2‐glycoprotein I predicts the risk of thrombosis in patients with the lupus anticoagulant

Abstract

Summary. Background: Lupus anticoagulant (LA) is a strong risk factor of thrombosis. However, a subgroup of patients positive for LA is unaffected by thrombosis and currently no predictive markers are available to identify patients positive for LA at increased risk for thrombosis. Objective: The aim of the study was to investigate whether anti‐beta‐2‐glycoprotein I (anti‐β2GPI) or anticardiolipin antibodies (ACA) are associated with an increased risk of thrombosis in patients persistently positive for LA. Patients and methods: A cohort of 87 consecutive patients persistently positive for LA was investigated, 55 with and 32 without a history of thrombosis. Immunoglobulin G (IgG) and M (IgM) antibodies against β2GPI and cardiolipin were determined by enzyme‐linked immunoassay. Results: Patients positive for LA with thrombosis had significantly higher levels of anti‐β2GPI IgG (median 16.7 standard units, interquartile range 3.0–75.2, P = 0.002) and of ACA IgG (41.1 IgG phospholipid units per mL, 8.9–109.0, P = 0.002) than those without thrombosis (2.6, 1.4–7.9 and 9.7, 4.6–22.1, respectively). Levels of anti‐β2GPI IgM and ACA IgM did not differ significantly between LA patients with and without thrombosis (P = 0.25 and 0.12, respectively). Elevated anti‐β2GPI IgG was associated with an increased risk for thrombosis (OR = 4.0, 95% CI 1.2–13.1), especially for venous thromboembolism (OR = 5.2, 95% CI 1.5–18.0). Conclusions: Increased levels of anti‐β2GPI IgG were associated with thrombosis. We conclude that anti‐β2GPI IgG levels above normal predict an increased risk of thrombosis in patients persistently positive for LA.

Biosensor Analysis of β2-Glycoprotein I–Reactive Autoantibodies: Evidence for Isotype-Specific Binding and Differentiation of Pathogenic from Infection-Induced Antibodies

“…The significance of IgM and IgA isotypes, however, is questionable (11)(12)(13). The finding that particularly high affinity anti-␤2GPI IgGs are associated with clinical signs (14,15 ) suggests that antigen-induced affinity maturation of polyreactive natural IgM antibodies and IgG isotype switching both contribute to the development of APS (16 ). Thus, avidity testing was considered an appropriate method for differentiating between pathogenic and nonpathogenic anti-␤2GPI (17 ).…”

A Comparison of Lupus Anticoagulant–Positive Patients With Clinical Picture of Antiphospholipid Syndrome and Those Without

“…Although the criterion of single test positivity was maintained at the recent Sydney consensus conference, the association of a single positive test with clinical events appears weaker. 6,8 Further studies will clarify the nature of the differences observed in the laboratory profiles of LAC positive subjects with or without relevant clinical events.From Clinical Cardiology (V.P., A.B. ),…”

The Management of Antiphospholipid Antibodies Affected Pregnancy

“…(33)(34)(35)(36)(37)(38). A multivariate analysis in a multicenter study has demonstrated that aβ2GPI and aPE, but not LA or aCL, were significantly associated with thrombosis (31).…”