IgG antibodies to plasminogen and their relationship to IgG anti-β2-glycoprotein 1 antibodies and thrombosis

Abstract

Reduced fibrinolytic activity has been described in primary antiphospholipid syndrome (PAPS) and may be responsible for thrombotic events. Some evidence supports a relationship between anti-plasminogen (PLG) antibodies, anti-beta(2)-glycoprotein 1 (beta(2)GP1) antibodies, and fibrinolysis, but their relationship is still unclear. The aim of study is to evaluate the association between IgG anti-beta(2)GP1 and IgG anti-PLG antibodies and thrombosis. Two groups of consecutive patients with PAPS and systemic lupus erythematosus (SLE): 32 patients with lupus anticoagulant (LAC), 32 patients without LAC, and 40 healthy controls were included. IgG against beta(2)GP1 and PLG antibodies were measured by enzyme-linked immunosorbent assay, and a value above the 99th percentile of the normal healthy control was considered as positive, and their interrelationship with thrombosis was evaluated by Pearson Chi-squared test. Cross-reactive antibodies binding to PLG and beta(2)GP1 were determined in a competitive and cross-inhibition assay. Levels of fibrinolytic activity in the presence of IgG fractions from patients and healthy controls were examined using a plasmin fluorogenic substrate assay. A high frequency of IgG anti-PLG antibodies (35.9%) was found in 64 patients, and its presence was associated with thrombosis (p = 0.001), which may be due to its ability to inhibit exogenous fibrinolysis. Coexistence of IgG anti-PLG and IgG anti-beta(2)GP1 antibodies was found in 11 of 64 patients and was related with thrombosis (p = 0.001). Cross-reactive antibody binding to PLG and beta(2)GP1 was found in IgG fractions from three patients and a monoclonal anti-beta(2)GP1 antibody BD4, and one of these three patients had thrombotic history. However, no significant association was found between IgG anti-PLG and IgG anti-beta(2)GP1 antibodies in patients. In conclusion, the prevalence of IgG anti-PLG was high in patients with PAPS and SLE and might relate with thrombosis. Cross-reactivity of IgG anti-beta(2)GP1 antibodies with PLG may occur in the sera of patients.