Differential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620279
Title:
Differential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes.
Authors:
Leete, P.; Willcox, A.; Krogvold, L.; Dahl-Jørgensen, K.; Foulis, A. K.; Richardson, S. J.; Morgan, Noel
Abstract:
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.
Citation:
Differential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes. 2016, 65 (5):1362-9 Diabetes
Publisher:
American Diabetes Association
Journal:
Diabetes
Issue Date:
May-2016
URI:
http://hdl.handle.net/11287/620279
DOI:
10.2337/db15-1615
PubMed ID:
26858360
Additional Links:
http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=26858360
Note:
This article is freely available. Click on the Additional Link above to access the full-text.
Type:
Journal Article
Language:
en
ISSN:
1939-327X
Appears in Collections:
Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLeete, P.en
dc.contributor.authorWillcox, A.en
dc.contributor.authorKrogvold, L.en
dc.contributor.authorDahl-Jørgensen, K.en
dc.contributor.authorFoulis, A. K.en
dc.contributor.authorRichardson, S. J.en
dc.contributor.authorMorgan, Noelen
dc.date.accessioned2017-03-14T12:49:27Z-
dc.date.available2017-03-14T12:49:27Z-
dc.date.issued2016-05-
dc.identifier.citationDifferential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes. 2016, 65 (5):1362-9 Diabetesen
dc.identifier.issn1939-327X-
dc.identifier.pmid26858360-
dc.identifier.doi10.2337/db15-1615-
dc.identifier.urihttp://hdl.handle.net/11287/620279-
dc.description.abstractType 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.en
dc.language.isoenen
dc.publisherAmerican Diabetes Associationen
dc.relation.urlhttp://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=26858360en
dc.rightsArchived with thanks to Diabetesen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
dc.titleDifferential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes.en
dc.typeJournal Articleen
dc.identifier.journalDiabetesen
dc.description.noteThis article is freely available. Click on the Additional Link above to access the full-text.en
dc.type.versionPublisheden

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