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Immunoregulatory molecules in patients with gestational diabetes mellitus

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Abstract

Induction of maternal-fetal immune tolerance is essential for the development of normal pregnancy. Impaired expression of costimulatory molecules may lead to intense inflammatory reaction, a mechanism involved in the pathophysiology of gestational diabetes mellitus (GDM). The aim of this study was to investigate whether immunoregulatory molecules are involved in the physiopathology of GDM. This case–control study included 30 healthy pregnant women and 20 GDM patients. Flow cytometry was used to assess peripheral blood T subpopulations (CD4+ and CD8+), the expression of immunoregulatory molecules (CD28, ICOS, CTLA-4, and PD-1) and activation markers (CD69 and HLA-DR). Compared to healthy women, GDM patients had a significantly higher frequency of CD4+CD69+ and CD8+CD69+ T cells; only patients with insulin-treated GDM had increased numbers of CD4+HLA-DR+ T cells. We also observed significantly higher percentages of CD4+CD28+HLA-DR+, CD3+CD4+ICOS+, CD3+CD4+PD-1+, CD8+CD28+CD69+, CD8+CD28+HLA-DR+, CD8+CTLA-4+HLA-DR+, and CD3+CD8+ICOS+ T cells and lower frequency of CD3+CD4+CTLA-4+, CD3+CD8+CTLA-4+, and CD8+ICOS+HLA-DR+ T cells in GDM patients compared to healthy pregnant women. This first study assessing costimulatory molecules in GDM patients shows that these patients have exacerbated markers of T cell activation along with CTLA-4 deficiency, findings that indicate that the maternal-fetal tolerance is compromised in these patients.

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Acknowledgments

This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Department of Obstetrics, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, 9 Andar, São Paulo, SP, 04939 032, Brazil

    Karen Priscilla Tezotto Pendeloski, Rosiane Mattar, Maria Regina Torloni, Caio Perez Gomes, Sandra Maria Alexandre & Silvia Daher

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  1. Karen Priscilla Tezotto Pendeloski
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  2. Rosiane Mattar
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Correspondence to Silvia Daher.

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Pendeloski, K.P.T., Mattar, R., Torloni, M.R. et al. Immunoregulatory molecules in patients with gestational diabetes mellitus. Endocrine 50, 99–109 (2015). https://doi.org/10.1007/s12020-015-0567-0

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