Patterns of Immune Infiltration in Endometriosis and Their Relationship to r-AFS Stages

Zhong, Qiyu; Yang, Fan; Chen, Xiaochuan; Li, Jinbo; Zhong, Cailing; Chen, Shuqin

doi:10.3389/fgene.2021.631715

Cited by 20 publications

(25 citation statements)

References 33 publications

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“…A recent paper identified the presence of naïve B cells, memory B cells and plasma cells in ectopic endometrial tissue, eutopic endometrial tissue and normal endometrial tissues by analysing 309 cases of gene transcriptome data in endometriosis research. A positive correlation of naïve B cells with CD4 memory activated T cells (r 2 = 0.7) and resting dendritic cells (r 2 = 0.62), and a negative correlation of naïve B cells with memory B cells (r 2 = −0.52), was observed in ectopic endometrial tissue ( Zhong et al , 2021 ). However, as the transcriptomic data were pulled from a public database, the patient characteristics were unclear (age, menstrual cycle phase when samples were obtained, etc.…”

Section: Discussionmentioning

confidence: 99%

The role of endometrial B cells in normal endometrium and benign female reproductive pathologies: a systematic review

Shen

O’Donnell

Leon

et al. 2021

Human Reproduction Open

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STUDY QUESTION What are the similarities and differences in endometrial B cells in the normal human endometrium and benign reproductive pathologies? SUMMARY ANSWER Endometrial B cells typically constitute less than 5% of total endometrial CD45+ lymphocytes, and no more than 2% of total cells in the normal endometrium, and while their relative abundance and phenotypes vary in benign gynaecological conditions current evidence is inconsistent. WHAT IS KNOWN ALREADY B cells are vitally important in the mucosal immune environment and have been extensively characterised in secondary lymphoid organs and tertiary lymphoid structures (TLSs), with the associated microenvironment germinal centre. However, in the endometrium, B cells are largely overlooked, despite the crucial link between autoimmunity and reproductive pathologies and the fact that B cells are present in normal endometrium and in benign female reproductive pathologies, scattered or in the form of lymphoid aggregates (LAs). A comprehensive summary of current data investigating B cells will facilitate our understanding of endometrial B cells in the endometrial mucosal immune environment. STUDY DESIGN, SIZE, DURATION This systematic review retrieved relevant studies from four databases (MEDLINE, EMBASE, Web of Science Core Collection, CINAHL) from database inception until November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS The search strategy combined the use of subject headings and relevant text words related to ‘endometrium’, ‘B cells’ and B cell derivatives such as ‘antibody’ and ‘immunoglobulin’. Non-benign diseases were excluded using cancer related free-text terms, and searches were limited to English language and human subjects. Only peer-reviewed research papers were included. Each paper was graded as ‘Good’, ‘Fair’, or ‘Poor’ quality based on the NEWCASTLE-OTTAWA quality assessment scale. Only ‘Good’ quality papers were included. MAIN RESULTS AND THE ROLE OF CHANCE Twenty-seven studies met the selection criteria and were included in this review: 10 cross-sectional studies investigated B cells in the normal endometrium; and 17 case-control studies compared the characteristics of endometrial B cells in control and benign female reproductive pathologies including endometritis, endometriosis, infertility, abnormal uterine bleeding, endometrial polyps and uterine fibroids. In all studies, B cells were present in the endometrium, scattered or in the form of LAs. CD20+ B cells were more abundant in patients with endometritis, but the data were inconsistent as to whether B cell numbers were increased in endometriosis and patients with reproductive pathologies. LIMITATIONS, REASONS FOR CAUTION Although only “good” quality papers were included in this systematic review, there are variations in patients’ age, diagnostic criteria for different diseases and sample collection time among included studies. Additionally, a large number of the included studies only used immunohistochemistry as the identification method for endometrial B cells, which may fail to provide an accurate representation of the numbers of endometrial B cells. WIDER IMPLICATIONS OF THE FINDINGS Histological studies found that endometrial B cells are either scattered or surrounded by T cells in LAs: the latter structure seems to be under hormonal control throughout the menstrual cycle and resembles TLSs that have been observed in other tissues. Further characterisation of endometrial B cells and LAs could offer insights to endometrial B cell function, particularly in the context of autoimmune-associated pathologies such as endometriosis. Additionally, clinicians should be aware of the limited value of diagnosing plasma cell infiltration using only CD138. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Finox Biotech. The authors have no conflicts of interests to declare. PROSPERO REGISTRATION NUMBER This systematic review was registered in PROSPERO in January 2020 (PROSPERO ID: CRD42020152915).

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Section: Discussionmentioning

confidence: 99%

The role of endometrial B cells in normal endometrium and benign female reproductive pathologies: a systematic review

Shen

O’Donnell

Leon

et al. 2021

Human Reproduction Open

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“…58 Also, with the progression of the disease, there is no significant difference in the total number of B cells. 33 7 OTHER CELLS…”

Section: B Lymphocytementioning

confidence: 99%

“…Among EC endometrium and eutopic (EU) endometrium, neutrophils do not change significantly. As the disease progresses, the fraction of this cell increases slightly 33 …”

Section: Innate Immune Cells In Endometriosismentioning

confidence: 99%

“…35 Also, the fraction of macrophage in the EC endometrium is significantly higher than the EU endometrium in these patients. 33 Macrophages are a key component of inflammatory processes, which are differentiated into proinflammatory (classical /M1) or antiinflammatory (alternative /M2) phenotypes depending on the microenvironment and peritoneal environment. 36,37 The number of both types of macrophages increases in endometriosis regardless of the stage of the disease.…”

Section: Macrophagementioning

confidence: 99%

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Immunopathogenesis of endometriosis: An overview of the role of innate and adaptive immune cells and their mediators

Moghaddam

Ansariniya

Seifati

et al. 2022

American J Rep Immunol

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Background Endometriosis is a chronic inflammatory disease associated with the growth and proliferation of endometrial‐like tissues outside the uterus. Although the exact etiology and mechanism of the pathogenesis of the disease have not been fully elucidated, the immune system cells and the mediators produced by them can be named as effective factors in the onset and progression of the disease. Aims We aim to attempt to review studies on the role of the immune system in endometriosis to better understand the pathogenesis of endometriosis. Content Abundant production of inflammatory mediators by neutrophils and macrophages and reduced cytotoxicity of defined cells promote endometriosis at the early stages of the disease. Following an increase in the inflammation of the environment, the body takes compensatory mechanisms to reduce inflammation and establish homeostasis. For this purpose, the body produces remodeling and anti‐inflammatory factors leading to slow conversion of the inflammatory environment into a non‐inflammatory environment with proliferative and immunosuppressive properties. Environmental conditions induce M2 macrophages, TH2 cells, and Tregs differentiation, promoting disease progression by producing angiogenic and immunosuppressive factors. However, the exact molecular mechanism involved in changing inflammatory to non‐inflammatory conditions is not yet fully understood. Implications Due to the common characteristics of endometriotic cells and cancer cells, most potential treatment options for endometriosis have been suggested due to the results of these methods in the treatment of cancer. In this pathway, immune system cells and soluble mediators can be used as targets.

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“…Women of childbearing age are the main patients with endometriosis, and the clinical manifestations of endometriosis are dysmenorrhea, abnormal menstruation, and sexual pain ( 3 ). When the staging standard of endometriosis reaches the stage III-IV of the revised American Fertility Society classification (r-AFS) scoring system, it will lead to infertility and greatly affect the daily life and fertility of patients ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Laparoscopic Surgery Combined With Leuprorelin in the Treatment of Endometriosis Associated With Infertility and Analysis of Influencing Factors for Recurrence

Sun

Fang

2022

Front. Surg.

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ObjectiveTo explore the curative effect of laparoscopic surgery combined with leuprorelin in the treatment of endometriosis with infertility and the related factors of recurrence after treatment.MethodsA total of 158 patients with endometriosis and infertility were selected in our hospital from January 2019 to June 2020. Patients were randomly divided into the control group and the observation group, with 79 patients in each group. Patients in the control group was treated by laparoscopy surgery combined with dydrogesterone, while those in the observation group was treated with laparoscopic surgery combined with leuprorelin. The hormone levels, recurrence rate, pregnancy rate and adverse reaction of the two groups were compared. Combined with clinical and pathological information, the related factors of postoperative recurrence were analyzed.ResultsAfter treatment, the levels of luteinizing hormone, follicle-stimulating hormone and estradiol in the observation group were lower than those in the control group (P < 0.05). The recurrence rate at 12 months after operation in the observation group was lower than that in the control group, and the pregnancy rate was higher than that in the control group (P < 0.05). However, there was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Preoperative dysmenorrhea was an independent risk factor for postoperative recurrence in patients with endometriosis, and postoperative pregnancy was a protective factor for postoperative recurrence in patients with endometriosis (P < 0.05).ConclusionLaparoscopy combined with leuprorelin in the treatment of endometriosis with infertility can improve hormone levels, increase the pregnancy rate and reduce the recurrence rate. Preoperative dysmenorrhea is an independent risk factor for postoperative recurrence, which should be quantified and included in the recurrence risk prediction model. Postoperative pregnancy can reduce the recurrence rate after operation, and patients with fertility requirements should be encouraged to make activ preparations for postoperative pregnancy.

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Patterns of Immune Infiltration in Endometriosis and Their Relationship to r-AFS Stages

Cited by 20 publications

References 33 publications

The role of endometrial B cells in normal endometrium and benign female reproductive pathologies: a systematic review

The role of endometrial B cells in normal endometrium and benign female reproductive pathologies: a systematic review

Immunopathogenesis of endometriosis: An overview of the role of innate and adaptive immune cells and their mediators

Efficacy of Laparoscopic Surgery Combined With Leuprorelin in the Treatment of Endometriosis Associated With Infertility and Analysis of Influencing Factors for Recurrence

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