Heparin and aspirin combination therapy restores T-cell phenotype in pregnant patients with antiphospholipid syndrome-related recurrent pregnancy loss

Abstract

Recurrent pregnancy loss (RPL) is the most common manifestation of anti-phospholipid syndrome (APS), and activated CD4⁺ T cells are involved in its pathogenesis. Treatment with low-molecular weight heparin (LMWH) and aspirin combination improves pregnancy outcome, however, its mechanism of action is unclear. We investigated the effect of this therapy on Th1/Th2 cells in 89 patients with APS-RPL. The results showed that serum cytokine levels, T cell phenotypes, and transcription factors' gene expression levels representing Th1 responses were higher, whereas those representing Th2 responses were lower in patients with APS-RPL at the time of early pregnancy. This Th1-bias was reversed in patients who had live birth after receiving the combination therapy at the time of delivery. Patients with miscarriages continued to exhibit Th1-bias. In conclusion, these data support a role of Th1-bias in the pathogenesis of APS-RPL and suggest restoring T-cell phenotype as a new immunomodulatory mechanism of LMWH/aspirin combination.

Keywords: Antiphospholipid syndrome; Aspirin; Low molecular weight heparin (LMWH); Recurrent pregnancy loss; Th1 polarization; Th2.