Germinal centre frequency is decreased in pancreatic lymph nodes from individuals with recent-onset type 1 diabetesReport as inadecuate




Germinal centre frequency is decreased in pancreatic lymph nodes from individuals with recent-onset type 1 diabetes - Download this document for free, or read online. Document in PDF available to download.

Diabetologia

, Volume 60, Issue 7, pp 1294–1303

First Online: 17 February 2017Received: 07 July 2016Accepted: 13 December 2016

Abstract

Aims-hypothesisPancreatic lymph nodes PLNs are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes.

MethodsImmunofluorescence staining was used to examine PLN sections from the following donor groups: non-diabetic n=15, non-diabetic islet autoantibody-positive n=5, recent-onset ≤1.5 years duration type 1 diabetes n=13, and longer-duration type 1 diabetes n=15. Staining for CD3, CD20 and Ki67 was used to detect primary and secondary germinal centre-containing follicles and CD21 and CD35 to detect follicular dendritic cell networks.

ResultsThe frequency of secondary follicles was lower in the recent-onset type 1 diabetes group compared with the non-diabetic control group. The presence of insulitis as evidence of ongoing beta cell destruction and diagnosis of type 1 diabetes at a younger age, however, did not appear to be associated with a lower frequency of secondary follicles. A higher proportion of primary B cell follicles were observed to lack follicular dendritic cell networks in the recent-onset type 1 diabetes group.

Conclusions-interpretationHistological analysis of rare PLNs from individuals with type 1 diabetes suggests a previously unrecognised phenotype comprising decreased primary B cell follicle frequency and fewer follicular dendritic cell networks in recent-onset type 1 diabetes.

KeywordsHistology Islet autoimmunity Pancreatic lymph nodes Type 1 diabetes AbbreviationsFDCFollicular dendritic cell

FFPEFormalin-fixed, paraffin-embedded

GADAGAD autoantibody

IA-2AIslet antigen-2 autoantibody

LTLymphotoxin

nPODNetwork for Pancreatic Organ Donors with Diabetes

pcCorrected p value

PLNPancreatic lymph node

TfhT follicular helper

TNFTumour necrosis factor

uMinnUniversity of Minnesota cohort

ZnT8AZinc transporter 8 autoantibody

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Author: Abby Willcox - Sarah J. Richardson - Lucy S. K. Walker - Sally C. Kent - Noel G. Morgan - Kathleen M. Gillespie

Source: https://link.springer.com/







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