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Interferon Alpha Treatment of Patients with Impaired Interferon Gamma Signaling

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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.

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Acknowledgments

We are grateful to M.E. Hanks for technical assistance. The research was supported by the Division of Intramural Research of National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, CRC B3-4233 MSC 1684, Bethesda, MD, 20892-1684, USA

    H. I. Bax, A. F. Freeman, L. Ding, A. P. Hsu, B. Marciano, E. Kristosturyan, 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

  2. Department of Internal Medicine, Division of Infectious Diseases, Erasmus Medical Center, Rotterdam, the Netherlands

    H. I. Bax

  3. Department of Pharmacy, National Institutes of Health Clinical Center, Bethesda, MD, USA

    T. Jancel

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  1. H. I. Bax
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Correspondence to E. P. Sampaio.

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Bax, H.I., Freeman, A.F., Ding, L. et al. Interferon Alpha Treatment of Patients with Impaired Interferon Gamma Signaling. J Clin Immunol 33, 991–1001 (2013). https://doi.org/10.1007/s10875-013-9882-5

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  • DOI: https://doi.org/10.1007/s10875-013-9882-5

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