Age-independent immune subtypes in Type 1 diabetes exhibit distinct post-onset progression rates and immunotherapeutic responses

Personalized prevention and treatment strategies for Type 1 diabetes (T1D), an autoimmune disease that targets the insulin-producing pancreatic β-cell, will require a deeper understanding of disease heterogeneity. We analyzed pre-intervention plasma samples, collected within 100 days of diagnosis, from 560 participants across six immunotherapy trials, using a bioassay in which plasma-induced transcription was measured in a well-controlled peripheral blood mononuclear cell population.

Microarray profiling identified 2,854 transcripts exhibiting high variation in at least five of the six trials. Unsupervised analyses concordantly divided the participants into two age-independent subgroups. The observed signatures were not due to relapsing and remitting immune activity as subgroup assignments were conserved in longitudinal analysis of post-baseline samples.