Causal Relationship Between Circulating Immune Cells and Recurrent Spontaneous Abortion: A Bidirectional Mendelian...

Area of Science:

• Immunology
• Reproductive Medicine
• Genetics

Background:

• Recurrent spontaneous abortion (RSA) is a common pregnancy complication with incompletely understood causes, though immunologic factors are implicated.
• Investigating the causal role of circulating immune cells in RSA is crucial for understanding its etiology.

Purpose of the Study:

• To evaluate the causal impact of circulating immune cells on recurrent spontaneous abortion (RSA).
• To identify specific immunophenotypes associated with the number of spontaneous abortions and recurrent miscarriage.

Main Methods:

• A comprehensive two-sample Mendelian randomization (MR) study was conducted.
• Analyzed 731 immunophenotypes of human peripheral blood lymphocytes for causal associations with spontaneous abortions and recurrent miscarriage.
• Performed sensitivity analyses to address heterogeneity, horizontal pleiotropy, and reverse causality.

Main Results:

• Eight immunophenotypes were significantly associated with the number of spontaneous abortions, including markers on CD4+ T cells, CD8+ T cells, and B cells.
• Two immunophenotypes, HLA DR on B cell and CD19 on naive-mature B cell, were associated with recurrent miscarriage.
• No evidence of heterogeneity, horizontal pleiotropy, or reverse causality was found.

Conclusions:

• The study establishes a strong genetic link between adaptive immune cells and recurrent spontaneous abortion (RSA).
• Identified immunophenotypes may serve as potential diagnostic biomarkers or therapeutic targets for RSA.