Unveiling Potential Blood Markers for Endometriosis Through the Integration and Experimental Validation of Immune Cell Traits Genome and Genome-Wide Associated Data.

Abstract

Background: While endometriosis (EM) has been previously associated with multiple immune factors, the causal relationship underlying these associations remains unclear.

Objective: In this study, Two-sample Mendelian randomization (MR) method was employed to investigate the causal relationship between 731 immune cell traits and EM based on tabulated data from genome-wide association studies (GWAS).

Methods: MR method includes inverse variance weighting (IVW), the weighted median (WM), MR-Egger, the weighted model, and the simple model. IVW is used as the primary method for judging causal effects. Peripheral blood was obtained from EM patients, and the positive immune cell phenotype was confirmed using flow cytometry.

Results: After P-value correction, our two-sample MR showed that CD28 on CD28+ DN (CD4-CD8-) had a suggestive causal relationship with EM (β =0.040, 95% CI =1.02-1.06, P =0.00029, P_FDR = 0.1984). The results of the other two main methods were similar: Weighted median (OR =1.031, 95% CI =1.00-1.07, P =0.082); MR-Egger (OR =1.032, 95% CI =1.10-1.06, P =0.044). The flow cytometry results indicated that the expression level of CD28 on CD28+ DN (CD4-CD-8) was significantly increased in the ectopic intima of EM patients.

Conclusion: Our study demonstrated a causal relationship between immune traits and EM, and the results were verified by clinical samples. The study may provide new biomarkers for the early diagnosis and immunotherapy of EM.