The role of complement components C1q, MBL and C1 inhibitor in pathogenesis of endometriosis

Archives of Gynecology and Obstetrics, Mar 2018

Justyna Sikora, Agnieszka Wróblewska-Czech, Marta Smycz-Kubańska, Aleksandra Mielczarek-Palacz, Anna Cygal, Andrzej Witek, Zdzisława Kondera-Anasz

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The role of complement components C1q, MBL and C1 inhibitor in pathogenesis of endometriosis

The role of complement components C1q, MBL and C1 inhibitor in pathogenesis of endometriosis Justyna Sikora 0 Agnieszka Wróblewska‑Czech 0 Marta Smycz‑Kubańska 0 Aleksandra Mielczarek‑Palacz 0 Anna Cygal 0 Andrzej Witek 0 Zdzisława KonderaA‑nasz 0 0 Department of Immunology and Serology, School of Pharmacy with the Division of Medical Analytics in Sosnowiec, Medical University of Silesia in Katowice , Jedności 8, 41-200 Sosnowiec , Poland 1 Justyna Sikora Purpose The purpose of the work was to evaluate possible associations between the complement components C1q, mannosebinding lectin (MBL) and C1 inhibitor (C1INH) with pathogenesis of endometriosis. Methods Concentrations of C1q, MBL and C1INH were measured by ELISA in peritoneal fluid (PF) in 80 women with or without endometriosis. Results Significantly higher PF levels of C1q, MBL and C1INH in women with endometriosis compared to control group were observed (p < 0.0001). A higher concentration of the studied parameter was found in PF of women at the early stage of the disease, as compared to women with advanced endometriosis (p < 0.0001). Conclusions Our research suggests that in the peritoneal cavity in women with endometriosis there are abnormal regulations of both the classical and lectin pathways of the complement system. This can suggest impairments in purification of peritoneal cavity from ectopic endometrial cells and augmented local inflammation in endometriosis patients. Complement components; Endometriosis; Peritoneal fluid Introduction Endometriosis is a common gynecological condition that affects approximately 10–12% of female population in reproductive age and up to 60% of infertile women [ 1 ]. It is defined as the presence and growth of endometrial-like tissues ectopically, most commonly on the pelvic peritoneum and ovaries [ 2 ]. Although endometriosis was first described more than 150 years ago, the pathogenesis of the disease is still poorly understood. The retrograde menstruation, a widely accepted theory, explained the possibility of endometrial cells appearing in the peritoneal cavity, but did not explain why cells were living there [ 3 ]. Recently, studies Department of Gynecology and Obstetrics, School of Medicine in Katowice, Medical University of Silesia in Katowice, Medyków 14, 40-752 Katowice, Poland have strongly suggested that local and systemic dysfunction of the immune system and inflammation must be involved in the survival of endometrial implants in ectopic localization [ 4 ]. In a physiological condition, well-functioning immune system mechanisms, eliminate endometrial cells from the peritoneal cavity. However, in women with endometriosis, it seems that the immune dysfunction and an altered peritoneal environment are associated with the reduced clearance of retrogradely transported endometrial fragments [ 5 ]. In the peritoneal fluid (PF) a high accumulation of peritoneal macrophages, regulatory T suppressor cells, NK cells and cytotoxic T lymphocyte with reduced killing capacity, cytokines, immunoglobulins (Ig) and inflammatory mediators can be found [ 6, 7 ]. One of the most important immune mechanisms taking part in the peritoneal clearance and inflammation is the complement system. The complement, a crucial component of the innate immune system, consists of over 30 small proteins which act as a cascade of proteases that activate each other in an enzymatic fashion, with effector mechanisms mediated by several specific cell receptors [ 8, 9 ]. The general function of the complement is to recognize microbial pathogens and other target cells and let them lyse. The complement cascade can be activated via one of three pathways: the classical pathway, the lectin pathway and the alternative pathway. These pathways are activated via different recognition molecules. The alternative complement pathway is initiated directly by the pathological organism. The classical pathway is started by the activation of C1q, by binding to ligands such as surface-bound IgM or IgG [10]. C1q is a plasma glycoprotein produced mainly by a wide range of immune cells including monocytes and macrophages, dendritic cells, and by epithelial and endothelial cells, as well as fibroblasts and trophoblasts [ 11 ]. The connection to the globular head domain of C1q with IgG or IgM containing immune complexes, causes an activation of C1r, which in turn activates C1s [ 8 ]. The lectin pathway is like the classical pathway. The cascade is initiated by binding of mannose-binding lectin (MBL) to mannose contained on the surface of the target cells. It is associated with various MBL-associated serine proteases (MASPs), which upon activation lead to the cleavage of C2 and C4 [ 12 ]. The activated C1 complex and MBL cleave the C4 and C2 components in the classical and lectin complement cascade, resulting in the assembly of the C3 convertase (C4b2a) [ 13 ]. In all three pathways the sequence of reactions leads to the generation of proteas (...truncated)


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Justyna Sikora, Agnieszka Wróblewska-Czech, Marta Smycz-Kubańska, Aleksandra Mielczarek-Palacz, Anna Cygal, Andrzej Witek, Zdzisława Kondera-Anasz. The role of complement components C1q, MBL and C1 inhibitor in pathogenesis of endometriosis, Archives of Gynecology and Obstetrics, 2018, pp. 1-7, DOI: 10.1007/s00404-018-4754-0