PROBLEM: Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed
NOVEL APPROACH: We conducted a phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (an Fc receptor–nonbinding anti-CD3 monoclonal antibody) involving relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease. Patients were randomly assigned to a single 14-day course of teplizumab or placebo, and follow-up for progression to clinical type 1 diabetes was performed with the use of oral glucose-tolerance tests at 6-month intervals
FINDINGS: Teplizumab delayed progression to clinical type 1 diabetes in high-risk participants
To date, there are no durable treatments or cures for T1D. However, we are learning a lot by studying samples from subjects in clinical trials and studies. I am a translational immunologist with greater than 15 years experience using human samples to understand underlying etiology, pathogenesis, disease heterogeneity and treatment response of subjects diagnosed with autoimmune diseases, with a strong focus on type 1 diabetes (T1D). We have recently found that CD8 exhausted cells are expanded in subjects with slower, less sever disease and are augmented by specific therapies. In contrast, we’ve found that defects in IL-2R signaling are associated with T1D susceptibility. Thus, I am focusing on exploring the role of IL-2/IL2RA pathway and CD8 T cell exhaustion in T1D. My research interests are strongly supported by, and complement, my efforts as the supervising PI of the Human Immunophenotyping Core (HIP Core). For the HIP Core, I play a pivotal role in collaborative efforts to discover immune signatures and underlying mechanisms by analyzing large cross-sectional, longitudinal, and clinical trial cohorts.