Diagnosis and evaluation of the anti-islet autoimmunity in human T1D using single cell analysis from peripheral blood.

This abstract has open access
Abstract Summary

Background: In the pre-clinical phase of disease, monitoring anti-islet antibodies is the only means to evaluate b cell destruction. As T1D is a T cell mediated disease, and can develop in agammaglobulinemia patients, detecting and profiling activated anti-islet CD4 T cells from peripheral blood would appear more appropriate and sensitive.

Methods: Single cell RNAseq of antigen-specific CD4 T cells in the islets of 4-8 week old NOD mice. FACS validation of identified upregulated cell surface markers on islet specific CD4 T cells. Isolation of peripheral blood T cells with similar FACS profile and sequencing. Validation of antigen specificity using pMHC tetramers in mice and humans.

Results: An exhaustive single cell analysis of infiltrating CD4 T cells in islets of pre-diabetic NOD mice has distinguish three main populations of cells based on surface phenotypes and signaling signatures. Using parabiosis, we demonstrate pathogenic CD4 T cells re-circulate and could be captured in peripheral blood using either surface markers and/or antigen-specific reagents. We have moved these results into translational studies to assess our ability to diagnose the islet-specific autoimmune reaction from peripheral blood. First, a cohort of 20 control and 20 established type 1 diabetic patients were examined for the possible presence of islet-activated CD4 T cells in blood. Unexpectedly, a population of activated cells could be isolated from T1D patients but not from control, most likely indicating that even in established disease, the autoimmune process is ongoing. Less surprisingly, in just-diagnosed patients, the same diagnostic population is increased to high percentages. The prognosis and treatment management value of following these CD4 cell population will be evaluated in a large follow-up cohort.

 

Submission ID :
IDS72230
Submission Type
Abstract Topics

Associated Sessions

Stanford University
The Scripps Research Institute
The Scripps Research Institute
The Scripps Research Institute
The Scripps Research Institute
The Scripps Research Institute
Rady Children's Hospital-San Diego
University of California, San Diego
The Scripps Research Institute

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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

Contact
British Society for Immunology
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