Linking the complement system to endometriosis pathogenesis: a systematic review of diagnostic potential
Year: 2026
Type: review
Abstract: Endometriosis (EM) is a chronic gynecological disorder affecting roughly 5-10% of women in their reproductive age, with symptom onset often occurring during adolescence but diagnosis frequently delayed for several years. Its pathogenesis is multifactorial, involving immunological, hormonal, genetic, and environmental factors. Increasing evidence suggests that immune dysregulation, particularly involving the complement system, a key effector of innate immunity and mediator of inflammatory responses, contributes to EM pathogenesis by sustaining chronic inflammation, angiogenesis, and lesion development. This review summarizes the available evidence on the involvement of complement components in EM pathogenesis and evaluates their potential use as biomarkers. A systematic literature search was performed in PubMed, Scopus, and Embase following PRISMA guidelines, including all eligible studies published up to July 2026. After full-text screening, 64 of 652 studies were selected and included in the final analysis. Overall, evidence supported a predominant involvement of the alternative complement pathway in EM, with complement component C3 emerging as the most extensively investigated molecule (35/64 studies). Evidence for the classical and lectin pathways was comparatively limited and heterogeneous. Moreover, several complement regulators emerged as differentially expressed in transcriptomic studies of endometriotic lesions. Overall, complement dysregulation appeared to be predominantly localized to the lesion microenvironment, while evidence of systemic complement activation remained limited. C3, C7, and FH emerged as the most consistently dysregulated molecules and appeared to be promising candidates for a complement-based biomarker panel for EM. Further validation in well-characterized and independent cohorts is required to determine their diagnostic value.
Source: Frontiers in Immunology
Institutions: IRCCS Materno Infantile Burlo Garofolo, University of Trieste
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7226003112