Blood and Islet Phenotypes Indicate Immunological Heterogeneity in Type 1 Diabetes
| Autor: | Deborah Kronenberg-Versteeg, Sarah J. Richardson, Abby Willcox, Katherine Marks, John A. Todd, Noel G. Morgan, Nurhanani Mohamed Nor, Jake Powrie, Polly J. Bingley, Megan Estorninho, Alan K. Foulis, Pia Leete, David B. Dunger, Catherine Guy, Anna Lorenc, Sefina Arif, Mark Peakman, Vy Nguyen, Emanuele de Rinaldis |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Type 1 diabetes
geography geography.geographical_feature_category business.industry Endocrinology Diabetes and Metabolism Autoantibody Disease medicine.disease medicine.disease_cause Islet Phenotype Proinflammatory cytokine Autoimmunity Diabetes mellitus Immunology Internal Medicine medicine Immunology and Transplantation business |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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