Cellular Immunity to β2-Glycoprotein-1 in Patients with the Antiphospholipid Syndrome

Abstract

Abstract Patients with antiphospholipid syndrome (APS) suffer recurrent thromboses, thrombocytopenia, and/or fetal loss in association with Abs that can be detected in phospholipid-dependent assays. Despite the name, the Igs associated with APS are predominantly directed against epitopes on phospholipid-binding plasma proteins, such as β2-glycoprotein-1 (β2GP1) and prothrombin. The aim of this study was to examine the cellular immune response to β2GP1 in patients with APS. Using a serum-free stimulation assay, PBMCs from 8 of 18 patients with APS proliferated to purified β2GP1 or to the β2GP1 present in serum, whereas no stimulation was observed by PBMCs from healthy individuals, patients with other autoimmune diseases, or anticardiolipin Ab-positive patients without histories of thromboses or fetal loss. The immune response was Ag-specific, requiring class II molecules, CD4+ T cells, and APCs, and was associated with a selective expansion of CD4+ but not CD8+ T cells. The proliferating T cells produced IFN-γ but not IL-4, indicating a bias toward a type 1 immune response. Chronic low grade stimulation of autoreactive β2GP1-specific, IFN-γ-producing Th1 CD4+ T cells may contribute to the high risk of thromboses and pregnancy failure in patients with APS.