Cellular immunity to beta(2)-glycoprotein-1 in patients with the antiphospholipid syndrome

Patients with antiphospholipid syndrome (APS) suffer recurrent thromboses, thrombocytopenia, and/or fetal loss in association with Abs that can be det ected in phospholipid-dependent assays. Despite the name, the Igs associate d with APS are predominantly directed against epitopes on phospholipid-bind ing plasma proteins, such as beta(2)-glycoprotein-1 (beta(2)GP1) and prothr ombin. The aim of this study was to examine the cellular immune response to beta(2)GP1 in patients with APS, Using a serum-free stimulation assay, PBM Cs from 8 of 18 patients with APS proliferated to purified beta(2)GP1 or to the beta(2)GP1 present in serum, whereas no stimulation was observed by PB MCs from healthy individuals, patients with other autoimmune diseases, or a nticardiolipin Ab-positive patients without histories of thromboses or feta l 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-gamma but not IL-4, indicating a bias toward a type 1 immune response. Chronic l ow grade stimulation of autoreactive beta(2)GP1-specific, IFN-gamma-produci ng Th1 CD4(+) T cells may contribute to the high risk of thromboses and pre gnancy failure in patients with APS.