Human leukocyte antigen-G, a ligand for the natural killer receptor KIR2DL4, is expressed by eutopic endometrium only in the menstrual phase

ObjectiveTo investigate menstrual cycle changes in expression by eutopic endometrium of a nonclassic human leukocyte antigen, HLA-G, which binds to the killer immunoglobulin-like receptor (KIR) 2DL4 (CD158d) on natural killer (NK) cells. Such antigens have been linked to endometriosis.DesignCase-control study.SettingUniversity hospital.Patient(s)We examined 20 Japanese women undergoing hysterectomy for endometriosis and 17 undergoing hysterectomy for myoma.Intervention(s)Immunohistochemical HLA-G staining of eutopic endometrium and peritoneal fluid (PF) cells from women with and without endometriosis. Flow cytometric analysis of PF NK cells from women with and without endometriosis.Main Outcome Measure(s)HLA-G staining in eutopic endometrium was quantified by image analysis. The KIR2DL4-expressing NK cells in PF were investigated by flow cytometry.Result(s)The HLA-G was expressed by eutopic endometrium only in the menstrual phase and not in the late proliferative or secretory endometrium. Intensity of HLA-G staining did not differ significantly between women with and without endometriosis. The HLA-G- expressing cells were detected in PF during the menstrual period. These cells are morphologically and flow cytometrically different from mesothelial cells and NK cells.Conclusion(s)The HLA-G expression is observed in eutopic endometrium only during the menstrual phase, and no differences were observed between women with and without endometriosis. Epithelial cells bearing HLA-G may enter the peritoneal cavity during retrograde menstruation, allowing the antigen to react locally with KIR2DL4.