Endometriosis and inflammatory immune responses: Indian experience

Abstract

Endometriosis is a public health disorder affecting ∼ 247 million women globally and ∼ 42 million women in India. Women with endometriosis suffer from dysmenorrhea, chronic pelvic pain, dyspareunia, dyschezia, fatigue, depression, and infertility leading to significant socioeconomic impact and morbidity. The etiology of endometriosis is not understood well even after 100 years of research. Currently, there is no permanent cure for endometriosis. The inflammatory immune response is one of the important features of etiopathogenesis of endometriosis and therefore understanding the inflammatory immune response would lead to a better understanding of this enigmatic disorder and may also lead to biomarker discovery for diagnosis of endometriosis. We investigated the autoimmune etiology of endometriosis in the Indian population. Using the proteomics approach, anti-endometrial antibodies (AEAs) were detected in Indian women with endometriosis [anti-endometrial antibodies - tropomyosin 3 (TPM3), stomatin-like protein2 (SLP-2), and tropomodulin 3 (TMOD3)]. The studies on AEAs provided a better understanding of autoimmune mechanisms in endometriosis. All three subtypes of endometriosis; superficial peritoneal, ovarian endometrioma, and deep infiltrating endometriosis were reported in Indian women. In this review, we discuss our experiences of the inflammatory immune response, autoimmunity, comorbidities, and clinical phenotypes in women with endometriosis in India.

Keywords: GWAS; WERF-EPHect; autoimmunity; clinical; endometriosis; genetic; inflammation; risk factors.

Figure 1

Map of India showing centers using the World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking harmonisation Project (WERF-EPHect) modified endometriosis patient questionnaire (EPQ), standard surgical form (SSF), and standard operating procedures (SOPs) for endometriosis research

Figure 2. Representative laparoscopic images of endometriosis sub-phenotypes and adhesions.

(A) Endometriosis on the surface of the left ovary; (B) Left endometrioma; (C) Endometrioma on left ovary with filmy adhesions; (D) DIE on both uterosacral ligaments; (E) DIE with dense adhesions on uterus, ovary, bowel, and left uterosacral ligament; (F) Web adhesions [UT-uterus, POD-pouch of douglas, OV-ovary, BO-bowel]

Figure 3. Representative laparoscopic images of endometriotic lesions.

(A) Red lesions on the right broad ligament; (B) Blue/ black lesions on the left broad ligament; (C) Brown lesion; (D) Yellow lesion; (E) Vascular lesions; (F) Allen-Masters peritoneal defect on the right broad ligament

Figure 4. Schematic presentation of the immune dysfunction involved in endometriosis.

(A) The female reproductive anatomy in healthy women and those with endometriosis. Endometriotic lesions are indicated as brown areas; endometriotic lesions contain epithelial cells (pink) and stromal cells (yellow), nerve fiber (blue), blood vessels (red). EMSC contributes to lesion establishment. (B1) Immune cell population involved during lesion development in ectopic locations; (B2) Immune cells involved in lesion maintenance; (C) Inflammatory mechanisms involved in the pathogenesis of endometriosis