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.

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doi.org/10.1007/s10875-013-9882-5, hdl.handle.net/1765/39460
Journal of Clinical Immunology
Erasmus MC: University Medical Center Rotterdam

Bax, H., Freeman, A. F., Ding, E., Hsu, A. P., Ferrier, M., Kristosturyan, E., … Holland, S. M. (2013). Interferon Alpha Treatment of Patients with Impaired Interferon Gamma Signaling. Journal of Clinical Immunology, 33(5), 991–1001. doi:10.1007/s10875-013-9882-5