Pia Leete1, Roberto Mallone2, Sarah J Richardson1, Jay M Sosenko3, Maria J Redondo4, Carmella Evans-Molina5. 1. Islet Biology Exeter (IBEx), Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, UK. 2. INSERM U1016, CNRS UMR8104, Cochin Institute, Sorbonne Paris Cité; Assistance Publique Hôpitaux de Paris, Service de Diabétologie, Cochin Hospital, INSERM and Assistance Publique Hôpitaux de Paris, Paris, France. 3. Department of Medicine and the Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA. 4. Department of Pediatrics, Baylor College of Medicine and the Texas Children's Hospital, Houston, TX, USA. 5. Departments of Medicine and Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine and the Roudebush VA Medical Center, 635 Barnhill Drive, MS 2031A, Indianapolis, IN, 46202, USA. cevansmo@iu.edu.
Abstract
PURPOSE OF REVIEW: To explore the impact of age on type 1 diabetes (T1D) pathogenesis. RECENT FINDINGS: Children progress more rapidly from autoantibody positivity to T1D and have lower C-peptide levels compared to adults. In histological analysis of post-mortem pancreata, younger age of diagnosis is associated with reduced numbers of insulin containing islets and a hyper-immune CD20hi infiltrate. Moreover compared to adults, children exhibit decreased immune regulatory function and increased engagement and trafficking of autoreactive CD8+ T cells, and age-related differences in β cell vulnerability may also contribute to the more aggressive immune phenotype observed in children. To account for some of these differences, HLA and non-HLA genetic loci that influence multiple disease characteristics, including age of onset, are being increasingly characterized. The exception of T1D as an autoimmune disease more prevalent in children than adults results from a combination of immune, metabolic, and genetic factors. Age-related differences in T1D pathology have important implications for better tailoring of immunotherapies.
PURPOSE OF REVIEW: To explore the impact of age on type 1 diabetes (T1D) pathogenesis. RECENT FINDINGS:Children progress more rapidly from autoantibody positivity to T1D and have lower C-peptide levels compared to adults. In histological analysis of post-mortem pancreata, younger age of diagnosis is associated with reduced numbers of insulin containing islets and a hyper-immune CD20hi infiltrate. Moreover compared to adults, children exhibit decreased immune regulatory function and increased engagement and trafficking of autoreactive CD8+ T cells, and age-related differences in β cell vulnerability may also contribute to the more aggressive immune phenotype observed in children. To account for some of these differences, HLA and non-HLA genetic loci that influence multiple disease characteristics, including age of onset, are being increasingly characterized. The exception of T1D as an autoimmune disease more prevalent in children than adults results from a combination of immune, metabolic, and genetic factors. Age-related differences in T1D pathology have important implications for better tailoring of immunotherapies.
Entities:
Keywords:
Age; Autoimmunity; C-peptide; Type 1 diabetes; β cell
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