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

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          Abstract

          The cause of endometriosis remains unknown. However, studies investigating the link between this condition and the immune system revealed several immunological abnormalities focused on cell-mediated immunity. As a major immune checkpoint, programmed cell death protein 1 (PD-1) displays an important inhibitory function in the maintenance of peripheral tolerance. The expression of PD-1 and its ligand (PD-L1) may contribute to continuous T cell activation and development of inflammation and injury of the tissue. To our knowledge, this is the first study evaluating frequencies of PD-1-positive T CD3 + cells (CD4 + and CD8 +) and B cells (CD19 +) in patients with endometriosis. Peripheral blood (PB) samples from 25 female patients and 20 healthy age and sex-matched subjects serving as controls were used in the study. Using flow cytometric analysis, we assessed the differences in the frequencies of PD-1-positive T and B lymphocytes in the study group and healthy individuals. Alteration of the PD-1/PD-L1 axis may contribute to the pathogenesis of endometriosis, as patients with advanced disease are characterized by higher frequencies of PD-1-positive T and B cells. Expression of PD-1 and PD-L1 on T and B cells could represent the hallmark of immune system reaction to chronic antigenic exposition in patients with endometriosis.

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          Most cited references46

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          The PD-1-PD-L pathway in immunological tolerance.

          Since the first observation of spontaneous autoimmune diseases in programmed cell death 1 (PD-1) knockout mice, PD-1 has been postulated to have essential roles in the regulation of autoimmunity but the precise mechanism was largely unknown. Recent studies clearly demonstrated that PD-1 has dual roles in immunological tolerance: induction and maintenance of peripheral tolerance. PD-1 ligands (PD-Ls) on antigen-presenting cells have been shown to switch off autoreactive T cells and induce peripheral tolerance, whereas those on parenchymal cells prevent tissue destruction by suppressing effector T cells to maintain tolerance. In addition, PD-1 and other immuno-inhibitory receptors have been shown to collaborate in the regulation of tolerance. Here, we review recent studies on the role of PD-1 in immunological tolerance and discuss possible clinical applications of PD-1 manipulation.
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            Endometriosis and infertility.

            Endometriosis is a debilitating condition characterized by high recurrence rates. The etiology and pathogenesis remain unclear. Typically, endometriosis causes pain and infertility, although 20-25% of patients are asymptomatic. The principal aims of therapy include relief of symptoms, resolution of existing endometriotic implants, and prevention of new foci of ectopic endometrial tissue. Current therapeutic approaches are far from being curative; they focus on managing the clinical symptoms of the disease rather than fighting the disease. Specific combinations of medical, surgical, and psychological treatments can ameliorate the quality of life of women with endometriosis. The benefits of these treatments have not been entirely demonstrated, particularly in terms of expectations that women hold for their own lives. Although theoretically advantageous, there is no evidence that a combination medical-surgical treatment significantly enhances fertility, and it may unnecessarily delay further fertility therapy. Randomized controlled trials are required to demonstrate the efficacy of different treatments.
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              Endometriosis: epidemiology and aetiological factors.

              Estimates of the frequency of endometriosis vary widely. Based on the few reliable data, the prevalence of the condition can reasonably be assumed to be around 10%. Although no consistent information is available on the incidence of the disease, temporal trends suggest an increase among women of reproductive age. This could be explained-at least in part-by changing reproductive habits. Numerous epidemiological studies have indicated that nulliparous women and women reporting short and heavy menstrual cycles are at increased risk of developing endometriosis; data on other risk factors are less consistent. These epidemiological findings strongly support the menstrual reflux hypothesis. Additional evidence in favour of this theory includes the demonstration of viable endometrial cells in the menstrual effluent and peritoneal fluid, experimental implantation and growth of endometrium within the peritoneal cavity, observation of some degree of retrograde menstruation in most women undergoing laparoscopy during menses, and an association between obstructed menstrual outflow and endometriosis.
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                Author and article information

                Contributors
                Journal
                Mediators Inflamm
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi
                0962-9351
                1466-1861
                2018
                25 November 2018
                : 2018
                : 7041342
                Affiliations
                1I Department of Gynecology, Medical University of Lublin, 16 Staszica Street, 20-081 Lublin, Poland
                2Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, 4a Chodzki Street, 20-093 Lublin, Poland
                3Department of Pharmaceutical Microbiology with Laboratory for Microbiological Diagnostics, Medical University of Lublin, 1 Chodzki Street, 20-093 Lublin, Poland
                4Augusta Kliniken Bochum, 26 Bergstrasse Street, 44791 Bochum, Germany
                Author notes

                Academic Editor: Carla Pagliari

                Author information
                http://orcid.org/0000-0002-0451-4741
                http://orcid.org/0000-0003-1634-0387
                http://orcid.org/0000-0002-0307-7535
                http://orcid.org/0000-0003-4841-6120
                Article
                10.1155/2018/7041342
                6286737
                30595667
                44c4a953-5233-40e7-86e2-306425dda4e0
                Copyright © 2018 Monika Walankiewicz et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 May 2018
                : 27 September 2018
                Funding
                Funded by: Uniwersytet Medyczny w Lublinie
                Award ID: DS460
                Award ID: MNsd521
                Categories
                Research Article

                Immunology
                Immunology

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