Jakinibs for the treatment of immune dysregulation in patients with gain-of-function signal transducer and activator of transcription 1 (STAT1) or STAT3 mutations

Abstract

Treatment of the autoimmune and immune-dysregulatory features of patients with STAT1 GOF or STAT3 GOF disease remains challenging. Jakinibs have been used to treat the severe immune-dysregulation in patients with either STAT1 GOF or STAT3 GOF mutations.

Figure I:

Improvement in Diseases Manifestations in STAT11 GOF and STAT3 GOF after treatment with jakinib and tocilzumab. A. Patient 3 with severe TPN-dependent enteropathy. Stool output significantly declined with intitiation of ruxolitinib. B. Patient 12 with lympocytic interstitial pneumonia. a. Chest CT imaging Pre-Tocilizumab shows diffuse ground glass pulmonary opacities and a few tiny cysts. b. Post-Tocilizumab chest CT imaging shows a slight overall decrease in the diffuse ground glass pulmonary opacities. c. Pre-Ruxolitinib chest CT imaging shows an increase in the diffuse ground glass pulmonary opacities compared to both prior CT exams. d. One month after starting Ruxolitinib shows a considerable decrease in the diffuse ground glass pulmonary opacities. e. One year after treatment with both tocilizumab, chest CT and ruxolitinib shows a further decrease in the diffuse ground glass pulmonary opacities. BiPAP, bilevel positive airway pressure ventilation. HFNC, high flow nasal cannula. NC, nasal cannula.