Interferon Alpha Treatment of Patients with Impaired Interferon Gamma Signaling

Patients with deficiency in the interferon gamma receptor (IFN-gamma R) are unable to respond properly to IFN-gamma and develop severe infections with nontuberculous mycobacteria (NTM). IFN-gamma and IFN-alpha are known to signal through STAT1 and activate many downstream effector genes in common. Therefore, we added IFN-alpha for treatment of patients with disseminated mycobacterial disease in an effort to complement their IFN-gamma signaling defect. We treated four patients with IFN-gamma R deficiency with adjunctive IFN-alpha therapy in addition to best available antimicrobial therapy, with or without IFN-gamma, depending on the defect. During IFN-alpha treatment, ex vivo induction of IFN target genes was detected. In addition, IFN-alpha driven gene expression in patients' cells and mycobacteria induced cytokine response were observed in vitro. Clinical responses varied in these patients. IFN-alpha therapy was associated with either improvement or stabilization of disease. In no case was disease exacerbated. In patients with profoundly impaired IFN-gamma signaling who have refractory infections, IFN-alpha may have adjunctive anti-mycobacterial effects.