Differential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes
| Autor: | Pia Leete, Sarah J. Richardson, Knut Dahl-Jørgensen, Noel G. Morgan, Alan K. Foulis, Lars Krogvold, Abby Willcox |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Adult CD4-Positive T-Lymphocytes Male medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Gastroenterology Autoimmune Diseases Cohort Studies 03 medical and health sciences Young Adult 0302 clinical medicine Diabetes mellitus Internal medicine Internal Medicine medicine Humans Insulin Young adult Age of Onset Child Pancreas Type 1 diabetes B-Lymphocytes business.industry Pancreatic islets Infant medicine.disease Antigens CD20 Immunohistochemistry United Kingdom 030104 developmental biology medicine.anatomical_structure Diabetes Mellitus Type 1 Pancreatitis Child Preschool Immunology Disease Progression Female Autopsy Age of onset business Insulitis Algorithms |
| Zdroj: | Diabetes. 65(5) |
| ISSN: | 1939-327X |
| Popis: | Type 1 diabetes (T1D) results from a T cell–mediated destruction of pancreatic β-cells following the infiltration of leukocytes (including CD8+, CD4+, and CD20+ cells) into and around pancreatic islets (insulitis). Recently, we reported that two distinct patterns of insulitis occur in patients with recent-onset T1D from the U.K. and that these differ principally in the proportion of infiltrating CD20+ B cells (designated CD20Hi and CD20Lo, respectively). We have now extended this analysis to include patients from the Network for Pancreatic Organ Donors with Diabetes (U.S.) and Diabetes Virus Detection (DiViD) study (Norway) cohorts and confirm that the two profiles of insulitis occur more widely. Moreover, we show that patients can be directly stratified according to their insulitic profile and that those receiving a diagnosis before the age of 7 years always display the CD20Hi profile. By contrast, individuals who received a diagnosis beyond the age of 13 years are uniformly defined as CD20Lo. This implies that the two forms of insulitis are differentially aggressive and that patients with a CD20Hi profile lose their β-cells at a more rapid rate. In support of this, we also find that the proportion of residual insulin-containing islets (ICIs) increases in parallel with age at the onset of T1D. Importantly, those receiving a diagnosis in, or beyond, their teenage years retain ∼40% ICIs at diagnosis, implying that a functional deficit rather than an absolute β-cell loss may be causal for disease onset in these patients. We conclude that appropriate patient stratification will be critical for correct interpretation of the outcomes of intervention therapies targeted to islet-infiltrating immune cells in T1D. |
| Databáze: | OpenAIRE |
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