Immune imbalance mediates the relationship between plasma vitamin D concentration and preeclampsia in Chinese pregnant women: A case-control study

Huanan Chen^1,2Yacong Bo³Yuan Cao⁴Jin Liu⁵Jiaqi Nie³Dandan Duan⁶Weifeng Dou³Xianlan Zhao⁷Wenjun Fu⁷Yi Zhang^5,8,9Yanhua Liu^1*

• ¹Department of Nutrition, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
• ²Department of Medical Record Management and Statistics, Shandong Provincial Qianfoshan Hospital, Jinan, China
• ³Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, China
• ⁴The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
• ⁵Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
• ⁶Department of Clinical Nutrition, Luoyang Dongfang People's Hospital, Luoyang, China
• ⁷Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
• ⁸School of Public Health, Zhengzhou University, Zhengzhou, China
• ⁹Zhongyuan Cell and Immunotherapy Laboratory, Henan Academy of Sciences, Zhengzhou, China

Vitamin D insufficiency is associated with an increased risk of preeclampsia. However, the role of T helper cell type 1 (Th1)/Th2 and Th17/regulatory T cell (Treg) balance in this association is unclear. We conducted a case-control study to explore the mediating effects of immune balance on the relationship between the plasma vitamin D concentration and preeclampsia. This study included 373 pregnant women recruited between March 2016 and February 2019 (192 cases and 181 controls). The cytokines as well as various T cell subsets were analyzed using ELISA and Flow cytometry, respectively. Spearman's correlation was used to investigate the association between vitamin D and cytokines as well as T cell subsets and mediating analysis was performed to identify the modifying effects of immune balance on this association. The Th1/Th2 and Th17/Treg ratios were negatively associated with the plasma concentration of 25-hydroxyvitamin D2 (25(OH)D2). Mediation analysis found that the Th1/Th2 as well as Th17/Treg ratios mediated the effect of 25(OH)D2 on the risk of preeclampsia, the mediating effects accounted for 59.59% and 40.45%, respectively. Our results provided preliminary evidence for a potential mediating role of the Th1/Th2 and Th17/Treg balance in the association between plasma 25(OH)D₂ and preeclampsia. Keeping higher levels of vitamin D, especially 25(OH)D2 might help maintain the immune balance and decrease the risk of preeclampsia.