Biomarkers for immune intervention trials in type 1 diabetes

After many efforts to improve and standardize assays for detecting immune biomarkers in type 1 diabetes (T1D), methods to identify and monitor such correlates of insulitis are coming of age. The ultimate goal is to use these correlates to predict disease progression before onset and regression following therapeutic intervention, which would allow performing smaller and shorter pilot clinical trials with earlier endpoints than those offered by preserved β-cell function or improved glycemic control. Here, too, progress has been made. With the emerging insight that T1D represents a heterogeneous disease, the next challenge is to define patient subpopulations that qualify for personalized medicine or that should be enrolled for immune intervention, to maximize clinical benefit and decrease collateral damage by ineffective or even adverse immune therapeutics. This review discusses the current state of the art, setting the stage for future efforts to monitor disease heterogeneity, progression and therapeutic intervention in T1D.

► Immune biomarkers provide relevant endpoints for immune intervention trials. ► T cells are more suitable than autoantibodies to provide such biomarkers. ► T-cell biomarkers yield information on therapeutic safety and immune efficacy. ► The latter may be associated or not with clinical efficacy. ► This information significantly improves the design and outcome of follow-up trials.