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). UPN727 cells were stimulated with CTLA4 treated patients (n=54) and placebo patients (n=20) plasma at baseline (BL), 3 month, 12 month and 24 month (total n=294 samples w/ 2 missing 3 month samples). Plus stimulated with our local Recent onset T1DM plasma (n=26). Gene expression analysis was perfromed in order to evaluate the transcriptional signature associated with T1D.