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Reduction of Circulating Neutrophils Precedes and Accompanies Type 1 Diabetes

机译:减少循环中性粒细胞的发生并伴有1型糖尿病

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摘要

Human type 1 diabetes (T1D) is an autoimmune disease associated with major histocompatibility complex polymorphisms, β-cell autoantibodies, and autoreactive T cells. However, there is increasing evidence that innate cells may also play critical roles in T1D. We aimed to monitor peripheral immune cells in early stages of T1D (i.e., in healthy autoantibody-positive subjects) and in more advanced phases of the disease (i.e., at disease onset and years after diagnosis). We found a mild but significant and reproducible peripheral neutropenia that both precedes and accompanies the onset of T1D. This reduction was not due to peripheral neutrophil cell death, impaired differentiation, or the presence of anti-neutrophil antibodies. Neutrophils were observed by electron microscopy and immunohistochemical analysis in the exocrine pancreas of multiorgan donors with T1D (both at onset and at later stages of the disease) and not in that of multiorgan donors with type 2 diabetes or nondiabetic donors. These pancreas-infiltrating neutrophils mainly localized at the level of very small blood vessels. Our findings suggest the existence of a hitherto unrecognized clinical phenotype that might reflect unexplored pathogenic pathways underlying T1D.
机译:人类1型糖尿病(T1D)是与主要组织相容性复合体多态性,β细胞自身抗体和自身反应性T细胞相关的自身免疫性疾病。但是,越来越多的证据表明,先天细胞也可能在T1D中起关键作用。我们的目标是在T1D的早期阶段(即健康的自身抗体阳性受试者)和疾病的更晚期阶段(即在疾病发作和诊断后数年)监测外周免疫细胞。我们发现轻度但显着且可重现的周围性白细胞减少症既在T1D发作之前也伴随其发作。这种减少不是由于外周中性粒细胞死亡,分化受损或抗中性粒细胞抗体的存在。通过电子显微镜和免疫组织化学分析,在患有T1D的多器官供体(在疾病的发作和后期)的外分泌胰腺中观察到嗜中性粒细胞,而在2型糖尿病或非糖尿病供体的多器官供体中则没有。这些胰腺浸润中性粒细胞主要位于非常小的血管水平。我们的研究结果表明,迄今为止存在尚未被认识的临床表型,可能反映了T1D潜在的未探索的致病途径。

著录项

  • 来源
    《Diabetes》 |2013年第6期|2072-2077|共6页
  • 作者单位

    San Raffaele Scientific Institute, Diabetes Research Institute, Milan, Italy,Vita-Salute San Raffaele University, Milan, Italy;

    San Raffaele Scientific Institute, Diabetes Research Institute, Milan, Italy,Tor-Vergata University, Rome, Italy;

    San Raffaele Scientific Institute, Diabetes Research Institute, Milan, Italy,Department of Internal Medicine, San Raffaele Hospital, Milan, Italy;

    San Raffaele Scientific Institute, Diabetes Research Institute, Milan, Italy;

    Department of Internal Medicine, San Raffaele Hospital, Milan, Italy,TrialNet Clinical Center, San Raffaele Hospital, Milan, Italy;

    Department of Internal Medicine, San Raffaele Hospital, Milan, Italy,TrialNet Clinical Center, San Raffaele Hospital, Milan, Italy;

    Diabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences, and Biochemistry, University of Siena Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy;

    Department of Experimental Pathology, University of Pisa, Pisa, Italy;

    San Raffaele Scientific Institute, Division of Regenerative Medicine, Stem Cells and Gene Therapy, Milan, Italy;

    Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Interdepartmental Center of Cytometry, Milan, Italy;

    San Raffaele Scientific Institute, Diabetes Research Institute, Milan, Italy,Department of Paediatrics and Neonatology, San Raffaele Hospital, Milan, Italy;

    Department of Paediatrics and Neonatology, San Raffaele Hospital, Milan, Italy;

    Department of Paediatric Orthopaedics, San Raffaele Hospital, Milan, Italy;

    Department of Urology, San Raffaele Hospital, Milan, Italy;

    Department of Immunohematology and Transfusion Medicine, San Raffaele Hospital, Milan, Italy;

    San Raffaele Scientific Institute, Diabetes Research Institute, Milan, Italy;

    Department of Endocrinology and Metabolism, University of Pisa, and Unit of Endocrinology and Metabolism of Transplantation, Azienda Ospedaliera Univeristaria Pisana, Pisa, Italy;

    Diabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences, and Biochemistry, University of Siena Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy;

    San Raffaele Scientific Institute, Diabetes Research Institute, Milan, Italy,Vita-Salute San Raffaele University, Milan, Italy,TrialNet Clinical Center, San Raffaele Hospital, Milan, Italy;

    San Raffaele Scientific Institute, Diabetes Research Institute, Milan, Italy,TrialNet Clinical Center, San Raffaele Hospital, Milan, Italy;

  • 收录信息 美国《科学引文索引》(SCI);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
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  • 入库时间 2022-08-18 03:46:25

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