HLA-G Is Expressed by the Glandular Epithelium of Peritoneal Endometriosis But Not in Eutopic Endometrium

Abstract

Many studies have pointed to differences in functional immune cell phenotypes between women with and those without endometriosis, but there is as yet no evidence that endometriotic cells escape immune surveillance. HLA-G is a major histocompatibility antigen known to help in regulating immune function. Because HLA-G appears to provide protection against cell-mediated cytolysis, the investigators studied its expression in endometriotic lesions and in eutopic endometrium. In an initial experiment, tissue blocks from 15 peritoneal endometriotic lesions and 12 samples of eutopic endometrium were compared for the extent of protein immunohistochemical staining using anti-HLA-G antibody. In addition, eutopic endometrial biopsies from 24 women with and 17 without endometriosis, along with 14 peritoneal endometriotic lesions, were examined by in situ hybridization for the presence of RNA transcript. All but one of the peritoneal endometriotic lesions examined (93%) exhibited distinct HLA-G immunostaining of the glandular epithelium but not the stroma. None of 12 samples of eutopic endometrium were distinctly stained. In 5 of the peritoneal lesions, 38% of the total, more than half of epithelial glandular cells were moderately to strongly stained. On RNA in situ hybridization, HLA-G transcript was localized to glandular epithelium in 13 of 14 peritoneal lesions (93%). No transcript was identified in samples of eutopic endometrium whether from women with endometriosis or disease-free control women. The finding that lesions of human endometriosis, but not eutopic endometrium, express a known immunomodulatory molecule such as HLA-G may help in developing novel treatment strategies. It seems possible that either peritoneal inflammation or cellular stress upregulates mechanisms that promote the survival of ectopic endometrium.