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

Abstract

<span><b>Background</b>: </span> <span><span>Recurrent miscarriage (RM) affects 2-5% of pregnant women. Paternal</span></span> 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 1 <em><span>a</span></em><span>, 25-dihydroxy-vitamin-D3 (vitamin D3) may improve the outcome.</span> <span><br/><b>Objectives</b>: </span> <span><span>To investigate the effect of vitamin D3 on the balance of two essential T</span></span> cells subsets, T helper (Th) 17 and T regulatory (Treg) cells, which contribute to the immune tolerance during pregnancy. <span><br/><b>Methods</b>: </span><span>The expression levels of CD4 and</span> 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. <span><br/><b>Results</b>: </span><span>Vitamin D3 therapy</span> 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 <span><</span><span>0.05).</span> <span><br/><b>Conclusion</b>: </span> <span><span>Considering that RM patients have a higher Th17/Treg ratio in peripheral</span></span> blood, vitamin D3 may be a candidate therapeutic approach in this disease.