From genes to reproductive health: Immune cell influences on abortion

Background: The relationship between dysregulation of the immune system and reproductive health, particularly in the context of abortion, is an area of critical research. Identifying the immunological factors that contribute to abortion could provide valuable insights into its prevention and management. Methods: This study used bidirectional two-sample Mendelian Randomization (MR) approach to evaluate the causal link between 731 immune cell features and the risk of abortion. The study analyzed GWAS data from 257,561 Europeans, including 7,069 cases and 250,492 controls, by utilizing genetic variation as instrumental variables. The immune phenotypes included several cell types, including B cells, T cells, TBNK cells, Treg cells, and monocytes. These were analyzed using the ’TwoSampleMR’ package in R software. Results: The study identified 34 immune phenotypes that have a significant causal relationship with abortion risk. Notably, Results from the B cell group showed a positive correlation between abortion and certain phenotypes, including Unsw mem %B cell, PB/PC %B cell, IgD+ CD24+ %B cell and Naive-mature B cell %lymphocyte. In the T cell group, certain maturation stages such as Naive CD8br %T cell and CD4 on CD45RA+ CD4+ exhibited negative causal links, whereas CCR7 on naive CD8br showed a positive association. The group of Treg cells showed both positive and negative causal relationships with abortion, highlighting the complexity of immune regulation in reproductive health. Conclusions: This study reflects the causal relationship between different subtypes of different immune cells and abortion. The results underscore the importance of the immune system in reproductive health and suggest potential therapeutic interventions targeting these immunological pathways.