CIRCULATING PLATELET-NEUTROPHIL AGGREGATES REPRESENT A PERIPHERAL BIOMARKER OF TYPE 1 DIABETES DEVELOPMENT IN NOD MICE

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Abstract Summary

Background: In certain autoimmune diseases, platelets and neutrophils are engaged in a vicious cycle of activation which promotes autoimmune disease. The aim of this study was to examine the contribution of platelet-neutrophil interactions to the development of Type 1 diabetes (T1D) in NOD mice. Methods: Platelet-neutrophil aggregates (PNAs) were analysed by flow cytometry in (i) the peripheral blood of NOD female mice at 3, 4, 6-8, 10-12, 16-18 weeks of age and at T1D onset and (ii) insulitis leukocytes harvested from islets isolated from additional NOD mice at the same corresponding ages. PNAs were identified as CD41+ve (platelet marker) Ly6Clo/Ly6Ghi neutrophils. Peripheral blood of male NOD mice at 3 -18 weeks of age (with characteristic low T1D incidence) and non-autoimmune control B6.SL mice were analysed in parallel. Results: Three waves of circulating PNAs were found in female NOD mice, peaking at 4 weeks, 10-12 weeks of age and at T1D-onset. These peak PNA levels correlated with the initiation of T1D autoimmunity in young NOD mice (from 3 weeks of age), marked infiltration of islets by inflammatory leukocytes (at 10-12 weeks) and the clinical onset of T1D. In contrast, male NOD mice demonstrated an elevation in PNAs only at 4 weeks of age. Islet PNAs were found to peak in NOD females at 4 weeks and 10-12 weeks of age. Islet PNAs therefore characterised the initiation of T1D autoimmunity in NOD mice (3 weeks) and contributed to the intra-islet leukocyte influx to damage beta cells in female mice at 10-12 wks. In female NOD mice the dynamic profile of islet-associated PNAs correlated with the PNA profile in peripheral blood. These findings suggest that PNA levels in peripheral blood represent a novel biomarker of T1D development.

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IDS6345
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The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia
The John Curtin School of Medical Research
The John Curtin School of Medical Research
The John Curtin School of Medical Research
The John Curtin School of Medical Research
The John Curtin School of Medical Research
The John Curtin School of Medical Research

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Event dates:
Thursday 25 October - Monday 29 October 2018

Abstract submission deadline:
Monday 14 May 2018

Abstract notification:
July 2018

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Monday 3 September 2018

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Monday 15 October 2018

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