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01.05.2015 | Article

Analysis of peri-islet CD45-positive leucocytic infiltrates in long-standing type 1 diabetic patients

verfasst von: Shiva Reddy, Nina Zeng, Hussam Al-Diery, Doran Jung, Clifton Yeu, Maximilian O. Joret, Mervyn J. Merrilees, Fiona Wu

Erschienen in: Diabetologia | Ausgabe 5/2015

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Abstract

Aims/hypothesis

The role of peri-islet CD45-positive leucocytes, as one component of insulitis, in beta cell death during human type 1 diabetes remains unclear. We undertook a case study, comparing and quantifying leucocytes in the peri- and intra-islet areas in insulin-positive and -negative islets, to assess whether peri-islet leucocytes are pathogenic to beta cells during type 1 diabetes.

Methods

Pancreatic sections from 12 diabetic patients (0.25–12 years of disease) and 13 non-diabetic individuals with and without autoantibodies were triple-immunostained for islet leucocytes, insulin and glucagon cells. Islets were graded for insulitis, enumerated and mapped for the spatial distribution of leucocytes in peri- and intra-islet areas in relation to insulin- and glucagon-immunopositive cells.

Results

In the non-diabetic autoantibody-negative group, the percentage of islets with insulitis was either absent or <1% in five out of eight cases and ranged from 1.3% to 19.4% in three cases. In the five non-diabetic autoantibody-positive cases, it varied from 1.5% to 16.9%. In the diabetic group, it was <1% in one case and 1.1–26.9% in 11 cases, with insulitis being absent in 68% of insulin-positive islets. Peri-islet leucocytes were more numerous than intra-islet leucocytes in islets with insulin positivity. Increasing numbers of exocrine leucocytes in non-diabetic autoantibody-positive and diabetic donors were also present.

Conclusions/interpretation

The prominence of peri-islet leucocytes in insulin-positive islets in most long-standing diabetic individuals suggests that they may be pathogenic to residual beta cells. Increasing numbers of leucocytes in the exocrine region may also participate in the pathogenesis of type 1 diabetes.

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Titel: Analysis of peri-islet CD45-positive leucocytic infiltrates in long-standing type 1 diabetic patients
verfasst von: Shiva Reddy
Nina Zeng
Hussam Al-Diery
Doran Jung
Clifton Yeu
Maximilian O. Joret
Mervyn J. Merrilees
Fiona Wu
Publikationsdatum: 01.05.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 5/2015
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-015-3519-6

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Analysis of peri-islet CD45-positive leucocytic infiltrates in long-standing type 1 diabetic patients