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Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, Australia
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
ß2-glycoprotein-1 (ß2GP1) and prothrombin.
The aim of this study was to examine the cellular immune response to
ß2GP1 in patients with APS. Using a serum-free
stimulation assay, PBMCs from 8 of 18 patients with APS proliferated to
purified ß2GP1 or to the ß2GP1 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-
but not IL-4,
indicating a bias toward a type 1 immune response. Chronic low grade
stimulation of autoreactive ß2GP1-specific,
IFN-
-producing Th1 CD4+ T cells may contribute to the
high risk of thromboses and pregnancy failure in patients with
APS.
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