Soluble immune checkpoints CTLA‐4, HLA‐G, PD‐1, and PD‐L1 are associated with endometriosis‐related infertility

Budi Santoso, Sa'adi A, Ashon Sa'adi, Ashon Sa’adi, Dwiningsih SR, Sri Ratna Dwiningsih, Arif Tunjungseto, Tunjungseto A, Widyanugraha MYA, Muhammad Yohanes Ardianta Widyanugraha, Mufid AF, Alfin Firasy Mufid, Nanda Yuli Rahmawati, Fadhil Ahsan
American journal of reproductive immunology (New York, N.Y. : 1989) · 2020 · vol. 84(4) , pp. e13296 · doi:10.1111/aji.13296 · PMID:32593225 · W3037664525
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This study found that elevated serum sPD-L1 and peritoneal fluid immune checkpoints are associated with endometriosis-related infertility and could serve as biomarkers.

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Abstract

PROBLEM: Soluble immune checkpoint molecules constitute the emerging novel mediators in immune regulation. Their role in the pathogenesis of endometriosis has not been fully addressed. In this study, we aimed to investigate the relationship between the clinical manifestation of endometriosis-associated infertility and the level of four soluble immune checkpoints: sCTLA4, sHLA-G, sPD-1, and sPD-L1. METHOD OF STUDY: The soluble immune checkpoint concentrations in serum and peritoneal fluid from 88 patients who underwent laparoscopy were evaluated by the enzyme-linked immunosorbent assay (ELISA). Clinical and hematological parameters were documented and analyzed. RESULTS: Endometriosis cases were evident to have significantly higher levels of serum sPD-L1 and all four molecules in peritoneal fluid compared to non-endometriosis control. Contrary, no significant differences were found in the concentration of serum sCTLA-4, sHLA-G and, sPD-1 between endometriosis and control group. There were significant positive correlations between serum and peritoneal fluid concentrations of sCTLA-4, sPD-L1, and sHLA-G. Serum sPD-L1 could discriminate endometriosis-related infertility to other pathological control. At a cutoff of 14,61 pg/mL, serum sPD-L1 had a sensitivity of 77% and specificity of 83%. Moreover, sPD-L1 level showed positive correlations with pelvic adhesion score and myeloid cell count. CONCLUSION: The elevated level of sPD-L1 in serum and immune checkpoint molecules in the peritoneal fluid could represent the hallmark of immune regulation in endometriosis. Serum sPD-L1 could serve as a potential noninvasive endometriosis biomarker. Also, the immune compartment related to the local immune checkpoint molecules may be implicated in biological mechanisms underlying endometriosis-related infertility.

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Condition tags

endometriosisinfertility

MeSH descriptors

Ascitic Fluid B7-H1 Antigen CTLA-4 Antigen Endometriosis HLA-G Antigens Immune Checkpoint Proteins Programmed Cell Death 1 Receptor Adult Ascitic Fluid B7-H1 Antigen Biomarkers CTLA-4 Antigen Disease Progression Endometriosis Female HLA-G Antigens Humans Immune Checkpoint Proteins Infertility Pregnancy

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References (30)

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