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Immunological Indicators of Recurrent Pregnancy Loss: A Mendelian Randomization Study

  • General Gynecology: Original Article
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Abstract

Recurrent pregnancy loss (RPL) is thought to be related to maternal-fetal immune tolerance disorders. Immune monitoring of RPL patients mainly involves two aspects: inflammatory factors and immune cells. However, most observational studies have reported controversial findings. This study aimed to confirm whether abnormal inflammatory factors and immune cells in peripheral blood may lead to RPL, and guide clinical immune monitoring. We demonstrated causality using two-sample Mendelian randomization. Sensitivity analysis, reverse Mendelian randomization and meta-analysis were used to enhance the effectiveness of the results. There was a causal relationship between the level of IL-12 (OR = 1.78, 95% CI = 1.25–2.55; P = 0.00149) and RPL for 41 inflammatory factors. We screened 5 groups of immune cell subtypes that were causally associated with RPL: switched memory B-cell absolute count (OR = 0.66, 95% CI = 0.49–0.87, P = 0.00406), IgD + CD24 + B-cell absolute count (OR = 0.69, 95% CI = 0.53–0.88, P = 0.00319), CD39 + resting CD4 regulatory T-cell %CD4 regulatory T-cell (OR = 0.86, 95% CI = 0.78–0.95, P = 0.00252), activated & resting CD4 regulatory T-cell %CD4 regulatory T-cell (OR = 0.89, 95% CI = 0.82–0.97, P = 0.00938) and CD45 RA + CD28-CD8 + T-cell %CD8 + T-cell (OR = 0.99, 95% CI = 0.98-1.00, P = 0.01231). In terms of inflammatory factors, a causal relationship between IL-12 and RPL in peripheral blood was confirmed. We also identified five immune cell phenotypes that play a protective role. This suggests that there may be protective B cells and CD8 + T-cell subsets in peripheral blood, and the protective effect of Tregs was proved again. Immune monitoring of peripheral blood in patients with RPL seems to be necessary and the foundation for precision medicine.

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Data Availability

The data that support the findings of this study are openly available in https://pubmed.ncbi.nlm.nih.gov/33239672, https://pubmed.ncbi.nlm.nih.gov/27989323, and https://pubmed.ncbi.nlm.nih.gov/32929287, reference number 19, 20 and 21.

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Acknowledgements

Thanks to all the open data providers whose excellent work is the basis of this study. The authors thank all the reviewers and editors for their useful suggestions for improving this study.

Funding

This study was funded by the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya hospital of Central South University [YX202212].

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Authors and Affiliations

  1. Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Pediatric Department of the 3rd Xiangya Hospital, Central South University, Changsha, 410078, China

    Jingrouzi Wu, Qingtai Cao, Jingnan Liao, Guangxiu Lu, Fei Gong, Ge Lin & Mingyi Zhao

  2. Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, 410078, China

    Jingrouzi Wu, Jingnan Liao, Yuan Li, Guangxiu Lu, Fei Gong & Ge Lin

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  1. Jingrouzi Wu
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Contributions

MZ and GL conceived and designed the study. JW drafted the manuscript. MZ, GL, and JW reviewed and revised the manuscript. QC, JL and JW collected the data and performed the data analysis. QC, FG, YL and JW produced the charts. All authors approved the final submission of the manuscript and agreed to be responsible for all aspects of the work.

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Correspondence to Ge Lin or Mingyi Zhao.

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Wu, J., Cao, Q., Liao, J. et al. Immunological Indicators of Recurrent Pregnancy Loss: A Mendelian Randomization Study. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01555-2

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