Circulating microRNAs as prognostic biomarkers of diabetes reversal in NOD mice treated with proinsulin- and IL-10 secreting Lactococcus Lactis in combination with low-dose anti-CD3

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Abstract Summary

Background

Oral administration of live genetically modified Lactococcus lactis (LL) secreting human proinsulin and IL-10 together with a short-course of low-dose anti-CD3 has been demonstrated to reverse T1D in NOD mice. Although LL therapy was successful in around 60% of NOD mice, 40% were metabolically non-responsive. Peripheral biomarkers to identify treatment-responsive populations may improve clinical translation of the LL therapy. 

Methods

TaqMan array cards were used to assess microRNA profiles in plasma samples collected at diabetes onset in glycemia-matched NOD mice prior to therapy, ultimately comparing 6 LL therapy responders and 6 non-responders. MicroRNAs differentially expressed in the profiling experiment were then validated by microRNA single assays in a second cohort of 15 responders and 15 non-responders.

Results

4 microRNAs were upregulated in plasma of LL therapy non-responders vs responders at disease onset: miR-34a, miR-125a-3p, miR-193b, and miR-365. The combination of miR-193b and miR-365 showed good prediction power (sensitivity: 86%; specificity: 80%). In silico pathway analysis, based on inferred microRNA target genes, identified possible metabolism-related signalling pathways predicting LL therapeutic success. The microRNA prognostic signature was specific for LL therapy, because the 4 microRNAs did not differ between plasma samples taken at disease onset from responders and non-responders given non-LL therapy (either anti-CD3 mono- or anti-CD3+IL-1Ra). Circulating microRNA signatures identified at disease onset in LL responders may be used to identify T1D patients that would benefit of this promising antigen-based immunotherapy.

Submission ID :
IDS25194
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Abstract Topics
Diabetes Unit, Department of Medicine, Surgery and Neuroscience, University of Siena and Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
Diabetes Unit Department of Medical Science, Surgery and Neuroscience, University of Siena, Italy; Umberto Di Mario Foundation ONLUS, Toscana Life Sciences, Siena
Laboratory of Experimental Medicine, University of Leuven, Belgium
Laboratory of Experimental Medicine, University of Leuven, Belgium
Diabetes Unit, Dept. of Medicine, Surgery and Neuroscience, University of Siena; Umberto Di Mario Foundation ONLUS, Toscana Life Sciences, Siena, Italy

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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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