P–305 The expression of innate immune factors in the eutopic endometrium of women with endometriosis

Abstract

Abstract Study question Is the expression of IL–17A and antimicrobial peptides (AMPs) altered in endometriosis? Summary answer IL–17A protein levels were similar in the endometrium of women with and without endometriosis but the expression of several AMPs was reduced in endometriosis. What is known already Chronic inflammation and aberrant immune signalling in the eutopic endometrium underlies the pathophysiology of endometriosis. Endometrial IL–17 levels have previously been shown by our group to be negatively correlated with successful pregnancy. IL–17 has also been associated with endometriosis. Among its immunomodulatory functions, IL–17 regulates the expression of several antimicrobial peptides (AMPs), highly conserved proteins that are involved in the innate immune response. Despite the well accepted paradigm of immune dysregulation in endometriosis, surprisingly little is known about the relationship between endometrial IL–17, AMPs and endometriosis, particularly in the context of infertility. Study design, size, duration This was a prospective cohort study. Endometrial biopsy samples were collected at the time of endometrial scratch testing, or during elective laparoscopy, over a 15-month period. The aim was to evaluate and compare IL–17A protein levels and the expression of specific AMPs (SLPI, elafin, beta-defensin 1, S100A7, S100A8, S100A9) [MW1] , in the endometrium of patients with endometriosis, and those without the disease. Participants/materials, setting, methods Thirty-two patients were recruited for the study, with 26 included in the final analysis. Biopsies were obtained at the time of planned endometrial scratch (mid-luteal phase) prior to ART (n = 7), or at the time of laparoscopy (n = 19). RNA was extracted and Q-PCR analysis for AMP transcript levels was performed. ELISA was carried out to quantify levels of IL–17A in endometrial tissue in a subgroup (n = 17). Main results and the role of chance: In our cohort IL–17A protein levels were not significantly different in the endometrium of patients with disease compared to those without (p = 0.3636). The expression of the AMPs elafin, SLPI, BD1 and S100A9, as measured by a Q-PCR transcript profiling approach, were found to be significantly reduced in the eutopic endometrium in cases of endometriosis as compared to cases without endometriosis. There was no significant difference in AMP expression between disease stages. No demonstrable difference in IL–17A protein levels, or AMP expression was detected between the proliferative and secretory phases of the menstrual cycle. Limitations, reasons for caution Numbers may not have been large enough to fully evaluate the impact of endometriosis stage or the effect of cycle phase. While all patients with endometriosis had surgical confirmation of disease, not all patients in the control cohort had a laparoscopy, though they had no clinical features suggestive of endometriosis. Wider implications of the findings: Our findings indicate that the innate immune environment of the eutopic endometrium is altered in endometriosis. Endometrial expression of AMPs was diminished in endometriosis, independent of disease stage. This work supports the model of dysregulated innate immune system in endometriosis, and reveals AMPs as novel immune players in disease pathogenesis. Trial registration number Not applicable