Patients with STAT1 gain-of-function (GOF) variants may present not only with chronic mucocutaneous candidiasis and other forms of immunodeficiency but also with a broad-spectrum of autoimmune manifestations, for which Janus kinase (JAK) inhibitors have been reported to be effective. Here, we report a pediatric patient with STAT1 GOF who developed recurrent pancreatitis in association with hypertriglyceridemia, potentially mediated by autoimmune mechanisms.
The patient is a 6-year-old female who developed oral thrush and herpes zoster at 2 years of age. She had previously been diagnosed with neonatal lupus in the setting of maternal Sjögren's disease. There was no family history of primary immunodeficiency.
At 4 years of age, she developed autoimmune hypothyroidism, with positive thyroglobulin Ab and microsomal Ab. Further evaluations revealed hypertriglyceridemia accompanied by episodes of acute pancreatitis and spleen atrophy. She was treated with levothyroxine, omega-3 supplementation, and a low-fat diet. Despite these interventions, she developed three additional episodes of pancreatitis occurring in the context of hypertriglyceridemia, requiring intermittent fenofibrate therapy to control hypertriglyceridemia. However, fenofibrate was later discontinued because of drug-induced hepatitis. To explore the underlying mechanism of hypertriglyceridemia, anti-GPIHBP1 autoantibody testing was performed and yielded a positive result. She later developed cholestatic hepatitis without concurrent pancreatitis, and liver biopsy findings are consistent with autoimmune hepatitis, with positivity for anti-smooth muscle antibodies.
Whole-genome sequencing identified a de novo heterozygous STAT1 variant of unknown significance (c.1199T>C, p.Leu400Pro). Given the history of unusual infections, multiple autoimmune manifestations, and the localization of the variant to a region previously implicated in STAT1 GOF, treatment with ruxolitinib and oral prednisolone was initiated, while antifungal prophylaxis was continued.
To our knowledge, this is the first case of STAT1 GOF who presented with recurrent pancreatitis associated with hypertriglyceridemia and the presence of anti-GPIHBPI1 autoantibodies. This case highlights a possible autoimmune link among STAT1 GOF, dyslipidemia, and pancreatitis, warranting further investigation and long-term therapeutic monitoring.
