The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Differential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes
Open accessAbstract
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.
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Rituximab, B-lymphocyte depletion, and preservation of beta-cell function
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Analysis of islet inflammation in human type 1 diabetes
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Self-citationIslet Pathology and the Pathogenesis of Type 1 and Type 2 Diabetes mellitus Revisited
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Self-citationB-Lymphocyte Depletion With Rituximab and β-Cell Function: Two-Year Results
Pescovitz, M. D., Greenbaum, C. J., Bundy, B., Becker, D. J., Gitelman, S. E., Goland, R., Gottlieb, P. A., Marks, J. B., Moran, A., Raskin, P., et al. (2014) · Diabetes Care · doi:10.2337/dc13-0626 · Cited by 287
Blood and Islet Phenotypes Indicate Immunological Heterogeneity in Type 1 Diabetes
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Self-citationInsulitis in human type 1 diabetes: The quest for an elusive lesion
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The diagnosis of insulitis in human type 1 diabetes
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Cited by
DiMeglio, L. A., Evans-Molina, C., & Oram, R. A. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31320-5 · Cited by 1,561
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Environmental risk factors for type 1 diabetes
Rewers, M., & Ludvigsson, J. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30507-4 · Cited by 676
Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?)
Roep, B. O., Thomaidou, S., van Tienhoven, R., & Zaldumbide, A. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-00443-4 · Cited by 623
The heterogeneous pathogenesis of type 1 diabetes mellitus
Ilonen, J., Lempainen, J., & Veijola, R. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0254-y · Cited by 494
Metadata
- Authors
- Leete, P., Willcox, A., Krogvold, L., Dahl-Jørgensen, K., Foulis, A. K., Richardson, S. J., & Morgan, N. G.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2016-02-08
- Volume
- 65
- Issue
- 5
- Pages
- 1362-1369
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2284464024
- Cited by
- 326
- References
- 26
- FWCI
- 21.53
- Type
- journal article
- Language
- en
- Open access
- green
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- Leete, P., Willcox, A., Krogvold, L., Dahl-Jørgensen, K., Foulis, A. K., Richardson, S. J., & Morgan, N. G. (2016). Differential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes. Diabetes. https://doi.org/10.2337/db15-1615
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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