Erschienen in:
01.07.2013 | Original Research
Interferon Alpha Treatment of Patients with Impaired Interferon Gamma Signaling
verfasst von:
H. I. Bax, A. F. Freeman, L. Ding, A. P. Hsu, B. Marciano, E. Kristosturyan, T. Jancel, C. Spalding, J. Pechacek, K. N. Olivier, L. A. Barnhart, L. Boris, C. Frein, R. J. Claypool, V. Anderson, C. S. Zerbe, S. M. Holland, E. P. Sampaio
Erschienen in:
Journal of Clinical Immunology
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Ausgabe 5/2013
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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.