دورية أكاديمية
Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes.
| العنوان: | Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes. |
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| المؤلفون: | Arif, Sefina, Leete, Pia, Nguyen, Vy, Marks, Katherine, Nor, Nurhanani Mohamed, Estorninho, Megan, Kronenberg-Versteeg, Deborah, Bingley, Polly J, Todd, John A, Guy, Catherine, Dunger, David B, Powrie, Jake, Willcox, Abby, Foulis, Alan K, Richardson, Sarah J, de Rinaldis, Emanuele, Morgan, Noel G, Lorenc, Anna, Peakman, Mark |
| المصدر: | Diabetes ; ISSN:1939-327X ; Volume:63 ; Issue:11 |
| بيانات النشر: | Silverchair Information Systems |
| سنة النشر: | 2014 |
| المجموعة: | PubMed Central (PMC) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.2337/db14-0365Test; https://pubmed.ncbi.nlm.nih.gov/24939426Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207393Test/ |
| DOI: | 10.2337/db14-0365 |
| الإتاحة: | https://doi.org/10.2337/db14-0365Test https://pubmed.ncbi.nlm.nih.gov/24939426Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207393Test/ |
| حقوق: | © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. |
| رقم الانضمام: | edsbas.36804593 |
| قاعدة البيانات: | BASE |
| DOI: | 10.2337/db14-0365 |
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