1. Interferon Alpha Treatment of Patients with Impaired Interferon Gamma Signaling.
- Author
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Bax, H., Freeman, A., Ding, L., Hsu, A., Marciano, B., Kristosturyan, E., Jancel, T., Spalding, C., Pechacek, J., Olivier, K., Barnhart, L., Boris, L., Frein, C., Claypool, R., Anderson, V., Zerbe, C., Holland, S., and Sampaio, E.
- Subjects
INTERFERON receptors ,CELLULAR signal transduction ,MYCOBACTERIAL diseases ,IN vitro studies ,GENE expression ,ANTI-infective agents - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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