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      Heparin Increases HLA-G Levels in Primary Antiphospholipid Syndrome

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          Abstract

          Objectives. The aim of this study was to investigate the HLA-G serum levels in Primary Antiphospholipid Syndrome (PAPS) patients, its impact on clinical and laboratory findings, and heparin treatment. Methods. Forty-four PAPS patients were age and gender matched with 43 controls. HLA-G serum levels were measured using an enzyme-linked immunosorbent assay (ELISA). Results. An increase in soluble HLA-G levels was found in patients compared to controls (3.35 (0–22.9) versus 1.1 (0–14), P = 0.017). There were no significant differences in HLA-G levels between patients with and without obstetric events, arterial thrombosis, venous thrombosis, or stroke. Sixty-six percent of patients were being treated with heparin. Interestingly, patients treated with heparin had higher HLA-G levels than ones who were not treated with this medication (5 (0–22.9) versus 1.8 (0–16) ng/mL, P = 0.038). Furthermore, patients on heparin who experienced obstetric events had a trend to increased HLA-G levels compared to patients who were not on heparin and did not have obstetric events (5.8 (0–22.9) versus 2 (0–15.2) ng/mL, P = 0.05). Conclusion. This is the first study to demonstrate that serum HLA-G levels are increased in APS patients. We also demonstrated that heparin increases HLA-G levels and may increase tolerance towards autoantigens.

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          Most cited references26

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          A class I antigen, HLA-G, expressed in human trophoblasts.

          The alpha chain of the human histocompatibility antigen HLA-G was identified as an array of five 37- to 39-kilodalton isoforms by the use of two-dimensional gel electrophoresis. Both cell-associated and secreted HLA-G antigens are prominent in first trimester villous cytotrophoblasts and are greatly reduced in third trimester cytotrophoblasts. Allelic variation was not detected, an indication that HLA-G is not obviously polymorphic in cytotrophoblasts. Among the following choriocarcinoma cell lines studied, HLA-G is expressed in JEG but not in Jar or BeWo. Expression of endogenous HLA-G genes has not been found in normal lymphoid cells. Thus, HLA-G is subject to both cell type-specific and developmental regulation and is expressed in early gestation human cytotrophoblasts.
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            A class I antigen, HLA-G, expressed in human trophoblasts

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              HLA-G1-expressing antigen-presenting cells induce immunosuppressive CD4+ T cells.

              We recently reported that HLA-G1-transfected antigen-presenting cells (HLA-G1+ APCs) were capable of inhibiting alloproliferative responses. The aim of the present work was to further study the function and the mechanisms of action of HLA-G1+ APCs. We show here that HLA-G1+ APCs are immunoinhibitory cells that (i) inhibit the proliferation of CD4+ T cells, (ii) shed HLA-G1 molecules that might provide extra, non-antigen-specific, inhibitory or proapoptotic signals, (iii) induce CD4+ T cell anergy, or at least long-term unresponsiveness, and (iv) cause the differentiation of CD4+ T cells into suppressive cells. Thus, HLA-G+ APCs might (i) be involved in the direct suppression of immune responses and (ii) contribute to long-term efficient immune escape or tolerance.
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                Author and article information

                Journal
                Clin Dev Immunol
                Clin. Dev. Immunol
                CDI
                Clinical and Developmental Immunology
                Hindawi Publishing Corporation
                1740-2522
                1740-2530
                2012
                13 May 2012
                : 2012
                : 232390
                Affiliations
                1Reumatologia Divisão, Faculdade de Medicina, Universidade de São Paulo, Sala 3105, Avenida Dr. Arnaldo, 455, 01246-903 São Paulo, SP, Brazil
                2Laboratório Clínico, RDO Diagnósticos, Avenida Brasil 1150, 01430-001 São Paulo, SP, Brazil
                3Edocrinologia Divisão, Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, Avenida Dr Enéas de Carvalho Aguiar 44, 05403-000 São Paulo, SP, Brazil
                Author notes
                *Jozélio Freire de Carvalho: jotafc@ 123456gmail.com and
                *Rosa Maria Rodrigues Pereira: rosamariarp@ 123456yahoo.com

                Academic Editor: E. Shevach

                Article
                10.1155/2012/232390
                3359668
                22654952
                b43ee784-59b7-4069-aabb-19afd38be9bd
                Copyright © 2012 Jozélio Freire de Carvalho 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
                : 22 December 2011
                : 3 March 2012
                : 5 March 2012
                Categories
                Clinical Study

                Immunology
                Immunology

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