HLA-G is upregulated in advanced endometriosis

Objective: To assess whether the HLA-G immunomodulatory protein is potentially involved in the pathophysiology of endometriosis or disease progression. Study design: Cross-sectional observational study of 227 women who underwent laparoscopy, being 146 for endometriosis excision and 81 for elective tubal ligation (control group). Soluble HLA-G (sHLA-G) levels in the serum and peritoneal fluid (PF), as well as the HLA-G protein expression in matched eutopic and ectopic endometrium of women with and without endometriosis were evaluated by ELISA and immunohistochemistry assays, respectively. Women with endometriosis were separated into groups according to the initial (I/II, n=60) and advanced (III/IV, n=86) stages of disease. sHLA-G measurement was performed only in women with matched serum and PF samples in both the control (CTRL; n=77) and endometriosis (EDT; I-II, n=60; n=83) groups. HLA-G protein expression was evaluated in 26 women with deep endometriosis (I-II, n=12; III-IV, n=14) and 22 controls. Results: Higher concentrations of sHLA-G (P=0.013) in the serum but not in the PF were observed in women with advanced endometriosis compared to the control group. In situ expression of HLA-G protein was also higher in ectopic (P=0.018) but not in eutopic endometrium of women with advanced endometriosis compared to control group. Conclusion: Our findings suggest that HLA-G upregulation in advanced stages may contribute to the state of immunosuppression in endometriosis as disease progresses.