Reduced frequency of perforin-positive CD8+ T cells in menstrual effluent of endometriosis patients

Timo Schmitz, Verena Hoffmann, Hoffmann V, Olliges E, Elisabeth Olliges, Alina Bobinger, Bobinger A, Popovici R, Roxana Popovici, Nößner E, Elfriede Nößner, Karin Meißner, Karin Meissner
Journal of Reproductive Immunology · 2021 · vol. 148 , pp. 103424 · doi:10.1016/j.jri.2021.103424 · PMID:34563756 · W3199182300
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Endometriosis patients have fewer perforin-positive CD8+ T cells in their menstrual effluent compared to healthy controls, indicating reduced cytotoxic potential.

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This study compared immunologic features in menstrual effluent (ME) and peripheral blood (PB) among 12 women with endometriosis (rASRM stages I–IV) and 11 healthy controls, using menstrual cup collection, flow cytometry on mononuclear cells from ME (MMC) and PB (PBMC), and ELISA measurement of cytokines (IL-6, IL-8, TNF-α) and adhesion molecules (ICAM-1, VCAM-1). Women with endometriosis had significantly fewer perforin-positive CD8+ T cells in ME, indicating reduced cytotoxic potential, along with lower plasma ICAM-1 levels, and ME-derived NK cells showed a lower perforin+ frequency than PB-derived NK cells. The authors found that MMC differed from PBMC by containing fewer T cells and more B cells, with a higher CD4/CD8 ratio and fewer Tregs in MMC. This paper is centrally about endometriosis — it analyzes perforin-positive cytotoxic immune cell frequencies in menstrual effluent as an immunological feature of endometriosis.

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Abstract

Endometriosis is a widespread disease and commonly reduces the life quality of those affected. Scientific literature indicates different underlying immunological changes. Frequently examined tissues are peripheral blood, endometrial tissue and peritoneal fluid. Yet, knowledge on immunological differences in menstrual effluent (ME) is scarce. In this study, between January 2018 and August 2019, 12 women with endometriosis (rASRM classification: stages I-IV) and 11 healthy controls were included. ME was collected using menstrual cups and venous blood samples (PB) were taken. Mononuclear cells were obtained from ME (MMC) and PB (PBMC) and analyzed using flow cytometry. Concentrations of cell adhesion molecules (ICAM-I and VCAM-I) and cytokines (IL-6, IL-8 and TNF-α) were measured using ELISA. CD8 + T cells obtained from ME were significantly less often perforin-positive in women with endometriosis compared to healthy controls. A comparison between MMC and PBMC revealed that MMC contained significantly less T cells and more B cells. The CD4/CD8 ratio was significantly higher in MMC, and Tregs were significantly less frequently in MMC. In ME, T cells and NK cells expressed significantly more CD69. NK cells obtained from ME were predominantly CD56bright/CD16dim and had a lower frequency of perforin + cells compared to PBMC NK cells. Moreover, ICAM-1 plasma levels were significantly reduced in women with endometriosis compared to healthy controls. In conclusion, CD8 + T cells obtained from the ME were significantly less perforin-positive in endometriosis patients indicating a reduced cytotoxic potential. MMC are distinctively different from PBMC and, thus, seem to be of endometrial origin.
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| Open Access Green | | as soon as is submitted to ZB. J. Reprod. Immunol. 148:103424 (2021) Endometriosis is a widespread disease and commonly reduces the life quality of those affected. Scientific literature indicates different underlying immunological changes. Frequently examined tissues are peripheral blood, endometrial tissue and peritoneal fluid. Yet, knowledge on immunological differences in menstrual effluent (ME) is scarce. In this study, between January 2018 and August 2019, 12 women with endometriosis (rASRM classification: stages I-IV) and 11 healthy controls were included. ME was collected using menstrual cups and venous blood samples (PB) were taken. Mononuclear cells were obtained from ME (MMC) and PB (PBMC) and analyzed using flow cytometry. Concentrations of cell adhesion molecules (ICAM-I and VCAM-I) and cytokines (IL-6, IL-8 and TNF-α) were measured using ELISA. CD8 + T cells obtained from ME were significantly less often perforin-positive in women with endometriosis compared to healthy controls. A comparison between MMC and PBMC revealed that MMC contained significantly less T cells and more B cells. The CD4/CD8 ratio was significantly higher in MMC, and Tregs were significantly less frequently in MMC. In ME, T cells and NK cells expressed significantly more CD69. NK cells obtained from ME were predominantly CD56bright/CD16dim and had a lower frequency of perforin + cells compared to PBMC NK cells. Moreover, ICAM-1 plasma levels were significantly reduced in women with endometriosis compared to healthy controls. In conclusion, CD8 + T cells obtained from the ME were significantly less perforin-positive in endometriosis patients indicating a reduced cytotoxic potential. MMC are distinctively different from PBMC and, thus, seem to be of endometrial origin. Altmetric Additional Metrics? Edit extra informations Login Publication type Article: Journal article Document type Scientific Article Keywords Endometriosis ; Menstrual Effluent ; Perforin ; T Cells; Intercellular-adhesion Molecule-1; Natural-killer-cells; Regulatory T-cells; Granzyme-b; Nk Cells; Pathogenesis; Lymphocytes; Involvement; Cancer; Serum ISSN (print) / ISBN 0165-0378 e-ISSN 0165-0378 Quellenangaben Volume: 148, Article Number: 103424 Publisher Elsevier Publishing Place Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland Reviewing status Peer reviewed Institute(s) Institute of Virology (VIRO) Grants Schweizer-Arau Foundation, Germany

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Condition tags

endometriosis

MeSH descriptors

B-Lymphocyte Subsets CD8-Positive T-Lymphocytes Endometriosis Killer Cells, Natural Menstrual Cycle Perforin T-Lymphocytes Adult B-Lymphocyte Subsets CD8-Positive T-Lymphocytes Cytokines Cytokines Cytotoxicity, Immunologic Endometriosis Female Humans Intercellular Adhesion Molecule-1 Intercellular Adhesion Molecule-1 Killer Cells, Natural Lymphocyte Count

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