Signal transducer and activator of transcription 1 gain-of-function (STAT1 GOF) mutations are the most common cause of chronic mucocutaneous candidiasis (CMC). We report the effect of oral ruxolitinib, an inhibitor of Janus kinase (JAK) family tyrosine kinases, on the clinical and immune status of a 3-year-old male with steroid-dependent severe autoimmunity due to a STAT1 GOF T385M mutation. The patient’s susceptibility to infection improved with antimicrobial prophylaxis and immunoglobulin replacement therapy, but he continued to exhibit severely disabling symptoms of autoimmunity. More than one-third of patients with STAT1 GOF mutations present with autoimmune manifestations, and this patient’s mutation was reported to cause CMC with autoimmunity. We analyzed the interleukin (IL)-17A and IFN-γ levels and immunophenotype by flow cytometry before and during treatment with ruxolitinib. The peripheral IL-17A level did not increase, but the IFN-γ level decreased after 4 months of therapy. The STAT1 phosphorylation level decreased significantly upon stimulation of patient cells with IFN-γ. Clinically, cytomegalovirus reactivation occurred, but was controlled. No other adverse effect was noted. We report the potential of JAK1/2 inhibition with ruxolitinib for both CMC and steroid-dependent autoimmunity. However, long-term administration is necessary, as the effect is not sustained after treatment is discontinued.

信号转导和转录激活因子 1 功能获得 (STAT1 GOF) 突变是慢性皮肤粘膜念珠菌病 (CMC) 的最常见原因。我们报告了口服鲁索替尼（一种 Janus 激酶 (JAK) 家族酪氨酸激酶抑制剂）对 3 岁男性因 STAT1 GOF T385M 突变而患有类固醇依赖性严重自身免疫病的临床和免疫状态的影响。患者对感染的易感性通过抗生素预防和免疫球蛋白替代疗法得到改善，但他继续表现出严重的自身免疫功能障碍症状。超过三分之一的 STAT1 GOF 突变患者存在自身免疫表现，据报道该患者的突变会导致 CMC 伴自身免疫。我们在鲁索替尼治疗前和治疗期间通过流式细胞术分析了白细胞介素 (IL)-17A 和 IFN-γ 水平和免疫表型。外周 IL-17A 水平没有增加，但 IFN-γ 水平在治疗 4 个月后下降。用 IFN-γ 刺激患者细胞后，STAT1 磷酸化水平显着降低。临床上，巨细胞病毒再激活发生，但得到控制。没有注意到其他不利影响。我们报告了鲁索替尼抑制 JAK1/2 对 CMC 和类固醇依赖性自身免疫的潜力。然而，长期给药是必要的，因为停止治疗后效果不会持续。用 IFN-γ 刺激患者细胞后，STAT1 磷酸化水平显着降低。临床上，巨细胞病毒再激活发生，但得到控制。没有注意到其他不利影响。我们报告了鲁索替尼抑制 JAK1/2 对 CMC 和类固醇依赖性自身免疫的潜力。然而，长期给药是必要的，因为停止治疗后效果不会持续。用 IFN-γ 刺激患者细胞后，STAT1 磷酸化水平显着降低。临床上，巨细胞病毒再激活发生，但得到控制。没有注意到其他不利影响。我们报告了鲁索替尼抑制 JAK1/2 对 CMC 和类固醇依赖性自身免疫的潜力。然而，长期给药是必要的，因为停止治疗后效果不会持续。