Imbalance of circulating CTLA4+ follicular helper and follicular regulatory T cells in obstetric antiphospholipid syndrome

Abstract

Obstetric antiphospholipid syndrome (OAPS) is a systemic autoimmune disease that is characterized clinically by a variety of obstetric manifestations (fetal death and recurrent abortions) and serologically by the presence of antiphospholipid antibodies (aPLs). Whether dysregulation of Follicular helper T (Tfh) and Follicular regulatory T (Tfr) cells contribute to the immunopathogenesis in OAPS is still unknown. We analyzed phenotypic characterizations of circulating Tfh cells and Tfr cells in OAPS patients and healthy individuals. CTLA4(Cytotoxic T lymphocyte antigen 4)+ Tfh cells and CTLA4+ Tfr cells were declined and CTLA4+ Tfr/Tfh ratio and IL-21 were increased in OAPS patients compared with healthy controls. Percentages of CTLA4+ Tfh cells and CTLA4+ Tfr cells were the lowest in OAPS patients whose antiphospholipid antibodies (aPL) were triple positive. Increased CTLA4+ Tfr/Tfh ratio was positively correlated with anti-β2 glycoprotein I (anti-β2GPI) IgM, Complement 4(C4) or IL-21 in OAPS. Increased Th17 subtype and decreased Th1, Th2 subtypes in Tfh cells and Tfr cells, increased effector memory subtype and decreased central memory subtype of Tfh cells and Tfr cells were also observed in OAPS compared with healthy individuals. Our data demonstrated that an imbalance of circulating CTLA4+ Tfh cells, and Tfr cells correlates with the immunopathogenesis of OAPS.