STAT1 Gain of Function, Type 1 Diabetes, and Reversal with JAK Inhibition

This case report describes a 17 year old male with STAT1 gai of function disease, a monogenic syndrome associated with autoimmune conditions including type 1 diabetes. The patient presented with chronic mucocutaneous candidiasis, hypogammaglobulinemia, and diabetic ketoacidosis. After genetic confirmation of the STAT1 mutation (c.1154C→T, pT385M), treatment with the JAK1/2 inhibitor ruxolitinib was initiated. Over 12 months, ruxolitinib therapy resolved infections, improved autoimmunity, and restored endogenous insulin production, allowing discontinuation of exogenous insulin. The patient remained euglycemic for over a year post treatment. This case suggests that JAK inhibition may reverse type 1 diabetes in STAT1 gain of function patients, highlighting a potential targeted therapy for this subset of autoimmune diabetes. Further studies are needed to evaluate the broader applicability of JAK inhibitors in type 1 diabetes management.

This case report describes a 17 year old male with STAT1 gai of function disease, a monogenic syndrome associated with autoimmune conditions including type 1 diabetes. The patient presented with chronic mucocutaneous candidiasis, hypogammaglobulinemia, and diabetic ketoacidosis. After genetic confirmation of the STAT1 mutation (c.1154C→T, pT385M), treatment with the JAK1/2 inhibitor ruxolitinib was initiated. Over 12 months, ruxolitinib therapy resolved infections, improved autoimmunity, and restored endogenous insulin production, allowing discontinuation of exogenous insulin. The patient remained euglycemic for over a year post treatment. This case suggests that JAK inhibition may reverse type 1 diabetes in STAT1 gain of function patients, highlighting a potential targeted therapy for this subset of autoimmune diabetes. Further studies are needed to evaluate the broader applicability of JAK inhibitors in type 1 diabetes management.