Elsevier

Immunology Letters

Volume 231, March 2021, Pages 43-48
Immunology Letters

Insights into the role of complement system in the pathophysiology of endometriosis

https://doi.org/10.1016/j.imlet.2021.01.005Get rights and content

Highlights

  • •

    There is immune system dysfunction in patients with endometriosis.

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    Complement system participate in the pathophysiology of the disease.

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    In this review we provide state-of-the-art knowledge about the role of the complement system in the pathophysiology of EM.

Abstract

Endometriosis (EM) is a gynecologic disorder characterized by the presence of endometrium-like tissue outside of normal location that affects up to 10 % of all women in reproductive age. The pathogenesis of endometriosis is not completely known. The relationship between complement and EM has already been demonstrated in some studies, indicating an important role in the pathophysiology of the disease, however, researches are scarce and sometimes controversial. The objective of this review is to bring state-of-the-art knowledge on the subject and promote better understanding of the complement system role in the pathophysiology of EM. We searched in databases up to December 2020 and found 1213 articles that were screened, from which were selected 54 articles from title and abstract. We found that there is a dysfunction of the immune system on endometriosis, including the complement system. Apparently, the complement system is dysregulated in endometriosis and several proteins of the three complement pathways presented serum levels altered in women with endometriosis compared with those without the disease. The most studied protein is C3. Future investigations on the innate immune response and complement system could offer a further understanding on the inflammatory pathogenesis of EM, which will support a new therapeutic plan.

Section snippets

Background

Endometriosis (EM) is a common gynecologic estrogen-dependent disorder characterized by the presence of endometrium-like tissue outside their normal location [1,2]. The main clinical symptoms are painful and mainly involve pelvic pain, infertility, dysmenorrhea, and dyspareunia; however, the majority of the cases of EM are asymptomatic [2,3]. Although the exact prevalence of EM is unknown, some studies estimate that it affects up to 10 % of women in the reproductive age [[1], [2], [3], [4]].

Objectives

The objective of this review is to provide state-of-the-art knowledge regarding this subject and to promote better understanding of the role of the complement system in the pathophysiology of EM.

Search strategy

This research was conducted by searching the following databases: PubMed, Scopus, Web of Science, and BVS-Biblioteca Virtual em Saúde (Health virtual Library). Original research reports (up to December 2020) that correlated EM with inflammation or complement were searched. The following keywords were used in the database search: “endometriosis,” “complement,” and “inflammation.”

First, 1213 articles were obtained. After thoroughly reading the titles and abstracts, we excluded studies that

Complement system

Complement is a complex system with more than 50 soluble and membrane-associated proteins, including receptors and regulatory proteins, that triggers immunological and inflammatory processes far beyond pathogen elimination [36]. Once activated, complement pathways converge in the formation of active enzyme complexes (C3 and C5 convertases) and culminate in the formation of the membrane attack complex (MAC), which is inserted into the target membrane leading to cell lysis. In addition to lytic

Endometriosis and complement system

EM is a chronic inflammatory disease with delayed diagnosis due to the absence of appropriate complementary examinations and biomarkers that can indicate the presence of the disease, and treatment mainly focuses on the symptoms (pain and/or infertility) [3,4]⁠. Inflammation is a key process in the pathogenesis of EM. Inflammatory cells such as neutrophils and macrophages participate in inflammation, and the latter is associated with estrogen, suggesting an immune response in EM [37]. However,

Therapeutic target in endometriosis

EM does not have a specific treatment regimen. Almost all currently available treatments of EM are suppressive and not curative. The treatment of EM-associated pain is based on suppressing estrogen production and inducing amenorrhea [48], such as combined hormonal contraceptives, progestagens, danazol, GnRH agonists, gestrinone, and aromatase inhibitors [2]. The treatment of EM-associated infertility is based on assisted reproductive technology [49]. Another option for EM treatment that

Conclusions

Previous studies have pointed out that EM has an important immunological factor and that the complement system acts incisively on the disease. It had been proved that the innate immune system participates in the physiopathology of EM. Despite this, there are only few studies about this theme, and some of them are controversial.

Therefore, is necessary to provide better insights into EM physiopathology. Future investigations on the innate immune response and complement system could offer a

Author contributions

Rahal, D participated in the design, planning, selection of papers and writing of the manuscript. Nisihara, R participated in the design, planning and revision of the manuscript. Andrade, F participated in the review and creation of images.

Funding

None.

Declaration of Competing Interest

No potential conflict of interest was reported by the author(s).

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