Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, CRC B3-4233 MSC 1684, Bethesda, MD 20892-1684, USA.
J Clin Immunol. 2013 Jul;33(5):991-1001. doi: 10.1007/s10875-013-9882-5. Epub 2013 Mar 20.
Patients with deficiency in the interferon gamma receptor (IFN-γR) are unable to respond properly to IFN-γ and develop severe infections with nontuberculous mycobacteria (NTM). IFN-γ and IFN-α are known to signal through STAT1 and activate many downstream effector genes in common. Therefore, we added IFN-α for treatment of patients with disseminated mycobacterial disease in an effort to complement their IFN-γ signaling defect. We treated four patients with IFN-γR deficiency with adjunctive IFN-α therapy in addition to best available antimicrobial therapy, with or without IFN-γ, depending on the defect. During IFN-α treatment, ex vivo induction of IFN target genes was detected. In addition, IFN-α driven gene expression in patients' cells and mycobacteria induced cytokine response were observed in vitro. Clinical responses varied in these patients. IFN-α therapy was associated with either improvement or stabilization of disease. In no case was disease exacerbated. In patients with profoundly impaired IFN-γ signaling who have refractory infections, IFN-α may have adjunctive anti-mycobacterial effects.
干扰素γ受体（IFN-γR）缺陷的患者无法对 IFN-γ做出适当反应，从而导致非结核分枝杆菌（NTM）的严重感染。IFN-γ 和 IFN-α 通过 STAT1 信号传递并激活许多下游共同的效应基因。因此，我们在治疗弥散性分枝杆菌病患者时添加了 IFN-α，以补充其 IFN-γ 信号缺陷。我们在最佳的抗感染治疗的基础上，根据缺陷的情况，为 4 名 IFN-γR 缺陷患者添加了 IFN-α 治疗。在 IFN-α 治疗期间，检测到 IFN 靶基因的体外诱导。此外，还观察到 IFN-α 在患者细胞和分枝杆菌中诱导的基因表达以及细胞因子反应。这些患者的临床反应各不相同。IFN-α 治疗与疾病的改善或稳定相关。在任何情况下，疾病都没有恶化。在那些 IFN-γ 信号严重受损且有难治性感染的患者中，IFN-α 可能具有辅助抗分枝杆菌的作用。
