Innate immune activity differentiate subtypes in new onset Type 1 diabetes that predict duration of the post-onset partial remission and correlate with responsiveness to CTLA4-Ig treatment

New measures are needed to predict type 1 diabetes disease trajectory. We have developed a sensitive array-based bioassay whereby patient plasma is used to induce transcription in healthy reporter leukocytes. Here we report a refined gene ontology-based inflammatory index (I.I.359) that is based upon expression levels of 359 transcripts identified in cross-sectional studies of new onset Type 1 diabetes patients and controls, where higher scores reflect greater inflammatory bias. We examined the relationship between I.I.359 measured at onset and the post-onset disease course in local patients as well as participants of the TrialNet CTLA4-Ig trial. In untreated patients, I.I.359 at baseline was highly variable and exhibited a significant inverse relationship with stimulated C-peptide AUC at 3, 6, 12, 18 and 24 months post-onset. Further, duration of the post-onset partial remission was negatively related to baseline I.I.359 and positively associated with the peripheral abundance of activated regulatory T cells (CD4+/CD45RA-/FoxP3high).

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Cabrera SM, Engle S, Kaldunski M, Jia S, Geoffrey R, Simpson P, Szabo A, Speake C, Greenbaum CJ, Type 1 Diabetes TrialNet CTLA4-Ig (Abatacept) Study Group., Chen YG, Hessner MJ