Study on the immunomodulatory mechanism of vitamin D in patients with unexplained recurrent spontaneous abortion

To investigate the mechanism of vitamin D level on the regulation of peripheral blood lymphocyte subsets and serum Th1/Th2 cytokines in patients with unexplained recurrent spontaneous abortion (URSA).

Eighty female patients with URSA attending Sichuan Jinxin Xinan Women's and Children's Hospital from January 2020 to May 2021 were selected as the study group, and 30 age-matched women with a history of healthy deliveries were chosen as the control group, and peripheral blood lymphocyte subpopulations and serum Th1/Th2 cytokines of people with different levels of vitamin D were detected in the study group by flow cytometry, respectively. The results of immune factors before and after supplementation were analyzed in 40 of these patients with low vitamin D levels. The results of lymphoid subpopulations and Th1/Th2 cytokines in 19 patients with normal pregnancy before and after vitamin D supplementation and after normal pregnancy were also analyzed comparatively.

(1) Serum 25(OH)D in the study group was lower than in the control group; peripheral blood Th cells, B cells and NK cells in the study group were higher than in the control group; IL-2, TNF-α, IFN-γ and IL-6 in the study group were higher than in the control group, while IL-4 and IL-10 in the study group were lower than in the control group (P < 0.05). (2) Th cells, B cells and NK cells of URSA patients in the vitamin D low level group were higher than those in the vitamin D normal group; serum cytokines IL-2, TNF-α and IFN-γ of patients in the vitamin D low level group were higher than those in the vitamin D normal group (P < 0.05); (3) Th cells, B cells and NK cells in URSA patients after vitamin D supplementation were lower than before vitamin D supplementation; serum cytokines IL-2, TNF-α and IFN-γ after vitamin D supplementation were lower than before vitamin D supplementation, IL-4 and IL-10 after vitamin D supplementation were higher than before vitamin D supplementation (P < 0.05), and there was no significant difference in IL-6 before and after vitamin D supplementation. (4) Th cells, B cells and NK cells in patients with normal pregnancy after vitamin D supplementation and after pregnancy were lower than those before vitamin D supplementation; serum cytokines IL-2, TNF-α and IFN-γ after vitamin D supplementation and after pregnancy were lower than those before vitamin D supplementation, and serum cytokines IL-4 and IL-10 after vitamin D supplementation and after pregnancy were higher than those before vitamin D supplementation, TNF -α, IFN-γ after pregnancy were lower than after vitamin D supplementation (P < 0.05), IL-6 was not significantly different before and after vitamin D supplementation and after pregnancy.

Vitamin D deficiency rate was high in URSA patients. Th、B、NK cells and IL-2, TNF-α, IFN-γ, IL-6 cytokines were high, while IL-6 and IL-10 were low in URSA patients. IL-2, TNF-α, IFN-γ cytokines and Th, B, NK cells were increased in vitamin D deficient URSA patients, and Vitamin D deficiency may be an important cause or aggravating factor of immune dysfunction in URSA patients. Vitamin D has an immunomodulatory effect on URSA patients, promoting successful pregnancy by down-regulating peripheral blood Th, B, and NK cells and IL-2, TNF-α, and IFN-γ cytokines, while up-regulating IL-4 and IL-10.