The Increase of Circulating PD-1- and PD-L1-Expressing Lymphocytes in Endometriosis: Correlation with Clinical and Laboratory Parameters

Walankiewicz, Monika; Grywalska, Ewelina; Polak, Grzegorz; Korona-Głowniak, Izabela; Witt, Elżbieta; Surdacka, Agata; Kotarski, Jan; Roliński, Jacek

doi:10.1155/2018/7041342

Cited by 33 publications

(29 citation statements)

References 59 publications

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“…Considering the above immune regulatory functions of soluble immune checkpoint molecules, it seems that they play a crucial role in the pathogenesis of endometriosis. Recently, the membrane‐bound PD‐1/PD‐L1 expressed by lymphocytes and endometrial tissues were described in endometriosis 17‐19 . In the current study, we hypothesize that soluble immune checkpoint molecules in peripheral circulation and peritoneal fluid will be elevated during endometriosis in infertile women.…”

Section: Introductionmentioning

confidence: 64%

“…Previous studies have reported a systemic anti‐inflammatory state in endometriosis patients with elevated concentration of serum IL‐10, which is known as one of the effector molecules in immune checkpoint signaling pathway 22,23 . The significantly higher level of sCTLA‐4 and sPD‐L1 in the sera of advanced‐stage endometriosis might also be the outcome of increased proteolytic cleavage of membrane forms from the local endometrial‐like cell lesions, which then circulate into the periphery 17,18,20 …”

Section: Resultsmentioning

confidence: 98%

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Soluble immune checkpoints CTLA‐4, HLA‐G, PD‐1, and PD‐L1 are associated with endometriosis‐related infertility

Santoso

Sa’adi

Dwiningsih

et al. 2020

American J Rep Immunol

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Problem: Soluble immune checkpoint molecules constitute the emerging novel mediators in immune regulation. Their role in the pathogenesis of endometriosis has not been fully addressed. In this study, we aimed to investigate the relationship between the clinical manifestation of endometriosis-associated infertility and the level of four soluble immune checkpoints: sCTLA4, sHLA-G, sPD-1, and sPD-L1. Method of study: The soluble immune checkpoint concentrations in serum and peritoneal fluid from 88 patients who underwent laparoscopy were evaluated by the enzyme-linked immunosorbent assay (ELISA). Clinical and hematological parameters were documented and analyzed. Results: Endometriosis cases were evident to have significantly higher levels of serum sPD-L1 and all four molecules in peritoneal fluid compared to non-endometriosis control. Contrary, no significant differences were found in the concentration of serum sCTLA-4, sHLA-G and, sPD-1 between endometriosis and control group. There were significant positive correlations between serum and peritoneal fluid concentrations of sCTLA-4, sPD-L1, and sHLA-G. Serum sPD-L1 could discriminate endometriosis-related infertility to other pathological control. At a cutoff of 14,61 pg/ mL, serum sPD-L1 had a sensitivity of 77% and specificity of 83%. Moreover, sPD-L1 level showed positive correlations with pelvic adhesion score and myeloid cell count. Conclusion: The elevated level of sPD-L1 in serum and immune checkpoint molecules in the peritoneal fluid could represent the hallmark of immune regulation in endometriosis. Serum sPD-L1 could serve as a potential noninvasive endometriosis biomarker. Also, the immune compartment related to the local immune checkpoint molecules may be implicated in biological mechanisms underlying endometriosisrelated infertility.

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Section: Introductionmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 98%

Soluble immune checkpoints CTLA‐4, HLA‐G, PD‐1, and PD‐L1 are associated with endometriosis‐related infertility

Santoso

Sa’adi

Dwiningsih

et al. 2020

American J Rep Immunol

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“…Hyporesponsiveness of T CD8+ cells may be contributing to their exhaustion [ 49 ]. In our previous research, we showed that advanced EMS was characterized by higher frequencies of programmed death-1 (PD-1)-positive T and B cells, which were the hallmark of T cell exhaustion [ 50 ]. Our results are interesting in light of a recently published study, in which CD200 overexpression on AML blasts suppressed CD4+ and CD8+ T lymphocyte function via the CD200/CD200R pathway.…”

Section: Discussionmentioning

confidence: 99%

CD200 and CD200R Expression on Peripheral Blood Lymphocytes and Serum CD200 Concentration as a New Marker of Endometriosis

Abramiuk

Grywalska

Korona-Głowniak

et al. 2020

JCM

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The causes of endometriosis (EMS) remain unknown; however, a number of immunological abnormalities contribute to the pathogenesis of the disease. The cluster of differentiation-200 (CD200) and its receptor (CD200R) maintain peripheral self-tolerance by negatively regulating immune responses. In this comparative cross-sectional study, we investigated the expression of CD200 and CD200R on T and B lymphocytes and the serum level of soluble CD200 (sCD200) using flow cytometry and ELISA, respectively. Peripheral blood samples were collected from 54 female patients and 20 healthy, age-matched controls. Results were tested for correlation with disease severity and selected clinical parameters. We demonstrated that the differences in sCD200 levels (p = 0.001), the frequencies of CD200-positive T and B lymphocytes (p < 0.001 and p = 0.004, respectively), and the frequencies of CD200R-positive T and B lymphocytes (p < 0.001 for all comparisons) in the study group correlated positively with disease severity. Receiver operating characteristic (ROC) analysis indicated that aberrant expression of CD200/CD200R might serve as a marker to distinguish between EMS cases. Finally, negative co-stimulatory factors may contribute to the induction and persistence of inflammation associated with EMS. It seems that it is essential to determine whether alteration in the CD200/CD200R pathway can be therapeutically targeted in EMS.

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“…88 Immunomodulatory factors may also be a result of lesion establishment, as suggested by greater numbers of circulating PD-1 þ T and B cells in advanced endometriosis. 89…”

Section: Genomic Regulation Of Cellular Pathways Involved In Endometrmentioning

confidence: 99%

Cellular Origins of Endometriosis: Towards Novel Diagnostics and Therapeutics

et al. 2020

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Endometriosis remains an enigmatic disease of unknown etiology, with delayed diagnosis and poor therapeutic options. This review will discuss the cellular, physiological, and genomic evidence of Sampson's hypothesis of retrograde menstruation as a cause of pelvic endometriosis and as the basis of phenotypic heterogeneity of the disease. We postulate that collaborative research at the single cell level focused on unlocking the cellular, physiological, and genomic mechanisms of endometriosis will be accompanied by advances in personalized diagnosis and therapies that target unique subtypes of endometriosis disease. These advances will address the clinical conundrums of endometriosis clinical care—including diagnostic delay, suboptimal treatments, disease recurrence, infertility, chronic pelvic pain, and quality of life. There is an urgent need to improve outcomes for women with endometriosis. To achieve this, it is imperative that we understand which cells form the lesions, how they arrive at distant sites, and what factors govern their ability to survive and invade at ectopic locations. This review proposes new research avenues to address these basic questions of endometriosis pathobiology that will lay the foundations for new diagnostic tools and treatment pathways.

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The Increase of Circulating PD-1- and PD-L1-Expressing Lymphocytes in Endometriosis: Correlation with Clinical and Laboratory Parameters

Cited by 33 publications

References 59 publications

Soluble immune checkpoints CTLA‐4, HLA‐G, PD‐1, and PD‐L1 are associated with endometriosis‐related infertility

Soluble immune checkpoints CTLA‐4, HLA‐G, PD‐1, and PD‐L1 are associated with endometriosis‐related infertility

CD200 and CD200R Expression on Peripheral Blood Lymphocytes and Serum CD200 Concentration as a New Marker of Endometriosis

Cellular Origins of Endometriosis: Towards Novel Diagnostics and Therapeutics

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