Altered Th17/Treg Ratio in Recurrent Miscarriage after Treatment with Paternal Lymphocytes and Vitamin D3: a Double-Blind Placebo-Controlled Study.

BACKGROUND Recurrent miscarriage (RM) affects 2-5% of pregnant women. Paternal lymphocyte immunotherapy is a common treatment for RM patients but the outcome has not been consistent. Therefore, combined therapy with other immunosuppressive drugs such as 1a, 25-dihydroxy-vitamin-D3 (vitamin D3) may improve the outcome. OBJECTIVES To investigate the effect of vitamin D3 on the balance of two essential T cells subsets, T helper (Th) 17 and T regulatory (Treg) cells, which contribute to the immune tolerance during pregnancy. METHODS The expression levels of CD4 and forkhead box protein 3 (FOXP3) in Treg cells, and the expression levels of CD4 and IL-17 in Th17 cells, were evaluated pre- and 3 months post-immunotherapy in RM patients treated with a combination of paternal lymphocytes and vitamin D3 compared with RM patients receiving lymphocyte immunotherapy alone. RESULTS Vitamin D3 therapy decreased the frequency of Th17 cells in addition to reducing the Th17/Treg ratio in peripheral blood of RM patients compared with the control group (p<0.05). CONCLUSION Considering that RM patients have a higher Th17/Treg ratio in peripheral blood, vitamin D3 may be a candidate therapeutic approach in this disease.