Dual role of humoral immunity and complement system in endometriosis

Endometriosis (EM) is a chronic gynaecological condition affecting approximately 5-10% of women of reproductive age. It is characterized by the presence of functional endometrial-like tissue outside the uterine cavity, most commonly involving the ovaries, peritoneum, and utero-sacral ligaments. The cyclical hormonal stimulation of these ectopic lesions leads to recurrent bleeding, chronic inflammation, tissue remodeling, chronic pelvic pain, and infertility. EM exhibits a complex and paradoxically "dual" immune profile. Although humoral immunity and the complement system are physiologically responsible for detecting and eliminating altered self-tissues, in EM these mechanisms are hijacked to promote lesion survival, angiogenesis, chronic pelvic inflammation, and tissue invasion. Numerous studies have established that epithelial and stromal cells within endometriotic lesions produce and secrete complement components, coagulation factors, and cytokines. The complement system represents a crucial arm of humoral immunity, acting as a bridge between innate and adaptive immune responses. Its activation is interconnected with other major proteolytic cascades, including the coagulation and contact systems. In concert with additional soluble host-defense factors, these pathways constitute an integrated network of innate and adaptive defenses. Emerging multi-omics studies have identified differential expression of genes and proteins belonging to these pathways in ectopic endometrial tissues, suggesting a significant contribution to EM pathogenesis.While several studies have demonstrated the local synthesis of these mediators within endometriotic lesions, their precise contribution to lesion development, disease progression, symptom severity, and recurrence remains poorly investigated. This Research Topic aims to gather research articles and literature reviews investigating the role of humoral immunity and soluble host-defense factors in EM. Particular emphasis will be placed on the molecular mechanisms regulating the local synthesis of these factors, the cross-talk among complement, coagulation, and kallikrein-kinin pathways, as well as their interactions with the broader immune system and the microbiota. To identify novel diagnostic biomarkers, prognostic indicators, intraoperative biomarkers, and therapeutic targets, a major goal of this Research Topic is to elucidate the signaling pathways, factors, and epigenetic mechanisms that drive the activation of humoral immune responses and the local synthesis of mediators within the endometriotic microenvironment.We welcome the submission of original articles, reviews, systematic reviews, and brief research reports addressing, but not limited to, the following topics:- The role of soluble host-defense factors – including complement components, cytokines, defensins, mucins, lectins, collectins, antimicrobial peptides – in the pathogenesis of EM.- The molecular and cellular mechanisms regulating the local production of soluble host-defense factors and activation of humoral immune responses within the endometriotic microenvironment. - The contribution of complement activation, coagulation pathway, and the contact system to lesion development, symptom manifestation, disease progression, and prognosis of EM.- The cross-talk between humoral and cellular innate immunity, as well as the interactions between humoral immunity and the microbiota in the pathogenesis of EM. Topic editors: Chiara Agostinis, Andrea Balduit, Roberta Bulla, Ilona Hromadnikova Source: https://www.frontiersin.org/research-topics/82119/dual-role-of-humoral-immunity-and-complement-system-in-endometriosis