Persistent long term endogenous insulin secretion in Type 1 diabetes is associated with an enhanced signature of islet specific immune regulation.

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Abstract Summary

Aim: The majority of people with long duration (>5years) T1D have a small number of functioning beta-cells, and a small proportion of these have relatively high C-peptide despite longstanding T1D. However, the clinical correlates and mechanisms for persistent beta cell function are not known. This study tested the hypothesis that endogenous insulin secretion may be associated with differences in immune phenotype, including the specificity, magnitude or polarization of islet specific immune responses.

 

Methods: We identified T1D patients in the top and bottom 20% of C-peptide secretion for their duration of diabetes and confirmed their C-peptide status using a MMTT (90-minute serum C-peptide >40pmol/L (CpHi) or undetectable (<3pmol/L, CpLo) and performed detailed immunological and genetic characterization on a cohort of 48 CpHi and 65 CpLo using a range of robust and validated assays.

Results: Age of diagnosis was older in CpHi (16(13,22) v 6(3,10)y p<0.0001) but we observed no difference in T1D genetic risk score.  Following adjustment for age, there was no difference in total frequencies of circulating leucocyte populations or FOXP3 Treg function. The total frequency of islet specific CD8 T cells was similar but CpHi had more autoantibody positive individuals (83 v 63% ?1 autoantibody positive, p=0.025). Despite the long duration since diagnosis, proliferation of CD4 T cells in response to islet antigens GAD65 or proinsulin was detected in both groups and was similar in frequency and magnitude. However, the quality of response CD4 T cell response differed significantly, with individuals from the CpHi group producing more IL-10 in response to proinsulin (12.0(2,23) v 4.9l (2,11) mg/mL, p=0.01).

ConclusionThese results suggest that a persistently high C-peptide in long standing T1D is associated with enhanced islet specific immune regulation and strengthen the hypothesis that islet specific IL-10 responses are associated with a slower rate of beta cell destruction. 

Submission ID :
IDS65114
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Abstract Topics
King's College London,
University of Exeter
City of Hope
University of Exeter Medical School
Royal Devon and Exeter NHS Foundation Trust
University of Exeter Medical School
Royal Devon and Exeter NHS Foundation Trust
King's College London
King's College London
University of Exeter Medical School
King's College London
University of Exeter Medical School

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KEY DATES

Event dates:
Thursday 25 October - Monday 29 October 2018

Abstract submission deadline:
Monday 14 May 2018

Abstract notification:
July 2018

Early registration deadline:
Monday 3 September 2018

Registration deadline:
Monday 15 October 2018

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British Society for Immunology
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