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

<p dir="ltr">Objective</p><p dir="ltr">Autoimmune Polyendocrine Syndrome type-1 (APS-1) is a rare monogenic autoimmune disorder that may manifest 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.</p><p dir="ltr">Research Design and Methods</p><p dir="ltr">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.</p><p dir="ltr">Results</p><p dir="ltr">Both patients exhibited improved glycemia. One who briefly required insulin recovered insulin independence two weeks post-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.</p><p dir="ltr">Conclusions</p><p dir="ltr">Teplizumab may preserve beta cell function in APS-1–associated T1D. Larger studies are needed to define efficacy, durability, and immunologic and tissue mechanisms in this rare context.</p><p><br></p><p><br></p>