Use of Teplizumab to Modulate Stage 2 Type 1 Diabetes in Two Individuals With Autoimmune Polyendocrine Syndrome 1

OBJECTIVE Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare, monogenic autoimmune disorder that may manifest as type 1 diabetes (T1D). Teplizumab, an anti-CD3 monoclonal antibody, delays progression of stage 2 T1D, but its effects in APS-1–associated diabetes are unknown. RESEARCH DESIGN AND METHODS We report clinical responses of two adolescents with APS-1 and stage 2 T1D who received 14-day courses of teplizumab. In one patient, pancreatic MRI and spectral immune cell phenotyping were performed before and after treatment. RESULTS Both patients exhibited improved glycemia. One who briefly required insulin recovered insulin independence 2 weeks after therapy. Pancreatic volume transiently increased, and circulating lymphocytes showed changes in homing receptors and senescence markers in the individual who underwent those studies. Nonpancreatic APS-1 manifestations were unchanged. CONCLUSIONS Teplizumab may preserve β-cell function in APS-1–associated T1D. Larger studies are needed to define efficacy, durability, and immunologic and tissue mechanisms in this rare context.