The over-activated peritoneal immune environment in endometriosis is characterised by a lack of PD-1 inhibition

Anna Tresso, Niharika Thota, Chloé James, Natasha Borash, Emily Brennan, Shima Bayat, Beverley Vollenhoven, Thomas T. Tapmeier
In: bioRxiv · 2024 · doi:10.1101/2024.08.30.610573 · W4402123492
preprint OA: green CC0
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Abstract

Abstract Background Endometriosis is characterised by chronic inflammation in the peritoneal cavity causing acute and chronic pelvic pain, largely explained by dysregulation in the immune environment within peritoneal fluid. The activation status of the peritoneal immune cells is unclear. In addition, a comparison with the status of the systemic immune system is desirable to explore avenues of diagnosis and treatment of endometriosis-related inflammation and pain. Objective(s) To investigate the immune environment in endometriosis in peritoneal fluid and blood by full-spectrum flow cytometry with a focus on activation and inhibition of immune cells. Study Design This was an observational study in patients undergoing laparoscopy for diagnosis or treatment of peritoneal endometriosis or for unrelated conditions; PF was collected from n=5 endometriosis patients and n=4 controls, blood from n=4 endometriosis patients and n=3 controls. Data were analysed for statistical significance using ANOVA, the Kruskal-Wallis or Mann-Whitney U test, with a p-value below 0.05 considered significant. Results We observed a prevailing of myeloid immune cells in the peritoneal fluid as opposed to lymphoid cells in the blood. The main differences between endometriosis and control samples, however, were found in the smaller compartments, i.e., in lymphoid populations in peritoneal fluid and myeloid populations in blood. PD-1 levels in peritoneal fluid endometriosis samples were significantly lower than in controls (p<0.05). Conclusion(s) The immune checkpoint PD-1 could be a new angle of treating endometriosis-related inflammation and pain in women suffering from this chronic and intractable condition. Tweetable Lack of PD-1 plays a role in endometriosis-related inflammation. AJOG at a glance The inflammatoru immune environment in endometriosis needs investigating as it iis causative of the pain, i.e., the predominant symptom. We found a lack of PD-1 expression on peritoneal fluid cells in endometriosis compared to controls. This could explain the persistent inflammation and open avenues of treatment.

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endometriosischronic_pelvic_pain

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