Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes.
Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes.
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作者：
Arif S;Leete P;Nguyen V;Marks K;Nor NM;Estorninho M;Kronenberg-Versteeg D;Bingley PJ;Todd JA;Guy C;Dunger DB;Powrie J;Willcox A;Foulis AK;Richardson SJ;de Rinaldis E;Morgan NG;Lorenc A;Peakman M
1型糖尿病的研究表明了潜在的疾病异质性，特别是β细胞丢失率、对免疫疗法的反应性，以及在有限的研究中，胰岛病理学。我们使用两种方法寻找不同免疫表型的证据。首先，我们通过对33例新诊断糖尿病儿童/青少年的自身抗体和自身反应性T细胞反应进行组合、多参数分析，确定血液自身免疫反应表型。多维聚类分析显示两个相同大小的患者聚集体，其特征为促炎反应（干扰素-γ阳性，多自身抗体阳性）和部分调节反应（白细胞介素-10阳性，少自身抗体阳性）。多自身抗体阳性的非糖尿病同胞在疾病进展的高风险表现出类似的集群。此外，从一个单独的队列的21名儿童/青少年最近诊断为1型糖尿病的尸检胰腺样本进行了免疫组织学检查。这揭示了两种不同类型的胰岛炎病变，可通过细胞浸润程度和B细胞的存在来区分，我们称之为“超免疫CD 20 Hi”和“少免疫CD 20 Lo”。值得注意的是，受试者仅具有一种浸润表型，并由此被划分为两个相等大小的组，这两个组在诊断时的年龄上显著不同，其中超免疫CD 20 Hi受试者年轻5岁。这些数据表明，潜在相关的胰岛和血液自身免疫反应表型，符合和之前的疾病。我们得出结论，不同的免疫病理过程（内型）可能是1型糖尿病的基础，对治疗和预防策略具有重要意义。
Studies in type 1 diabetes indicate potential disease heterogeneity, notably in the rate of β-cell loss, responsiveness to immunotherapies, and, in limited studies, islet pathology. We sought evidence for different immunological phenotypes using two approaches. First, we defined blood autoimmune response phenotypes by combinatorial, multiparameter analysis of autoantibodies and autoreactive T-cell responses in 33 children/adolescents with newly diagnosed diabetes. Multidimensional cluster analysis showed two equal-sized patient agglomerations characterized by proinflammatory (interferon-γ–positive, multiautoantibody-positive) and partially regulated (interleukin-10–positive, pauci-autoantibody–positive) responses. Multiautoantibody-positive nondiabetic siblings at high risk of disease progression showed similar clustering. Additionally, pancreas samples obtained post mortem from a separate cohort of 21 children/adolescents with recently diagnosed type 1 diabetes were examined immunohistologically. This revealed two distinct types of insulitic lesions distinguishable by the degree of cellular infiltrate and presence of B cells that we termed “hyper-immune CD20Hi” and “pauci-immune CD20Lo.” Of note, subjects had only one infiltration phenotype and were partitioned by this into two equal-sized groups that differed significantly by age at diagnosis, with hyper-immune CD20Hi subjects being 5 years younger. These data indicate potentially related islet and blood autoimmune response phenotypes that coincide with and precede disease. We conclude that different immunopathological processes (endotypes) may underlie type 1 diabetes, carrying important implications for treatment and prevention strategies.
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影响因子：
168.9
作者：
Sherry, Nicole;Hagopian, William;Ludvigsson, Johnny;Jain, Sunil M.;Wahlen, Jack;Ferry, Robert J., Jr.;Bode, Bruce;Aronoff, Stephen;Holland, Christopher;Carlin, David;King, Karen L.;Wilder, Ronald L.;Pillemer, Stanley;Bonvini, Ezio;Johnson, Syd;Stein, Kathryn E.;Koenig, Scott;Herold, Kevan C.;Daifotis, Anastasia G.
通讯作者：
Daifotis, Anastasia G.
影响因子：
15.9
作者：
Peakman, M;Stevens, EJ;Chicz, RM
通讯作者：
Chicz, RM
影响因子：
15.9
作者：
Skowera, Ania;Ellis, Richard J.;Peakman, Mark
通讯作者：
Peakman, Mark
影响因子：
7.7
作者：
Brusko, TM;Wasserfall, CH;Atkinson, MA
通讯作者：
Atkinson, MA
影响因子：
7.7
作者：
Velthuis JH;Unger WW;Abreu JR;Duinkerken G;Franken K;Peakman M;Bakker AH;Reker-Hadrup S;Keymeulen B;Drijfhout JW;Schumacher TN;Roep BO
通讯作者：
Roep BO