Interferon Alpha Treatment of Patients with Impaired Interferon Gamma Signaling
| Autor: | Alexandra F. Freeman, Hannelore I. Bax, Reginald J. Claypool, Kenneth N. Olivier, Timothy Jancel, Li Ding, Christa S. Zerbe, Joseph Pechacek, Lisa A. Barnhart, B.E. Marciano, Amy P. Hsu, Christine Spalding, Elizabeth P. Sampaio, Ervand Kristosturyan, Cathleen Frein, Victoria L. Anderson, Lisa Boris, S.M. Holland |
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| Přispěvatelé: | Internal Medicine |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Immunology Alpha interferon Gene Expression Article Mycobacterium Interferon-gamma Young Adult Interferon-gamma receptor medicine Immunology and Allergy Humans Interferon gamma STAT1 Interferon alfa Cells Cultured Receptors Interferon Mycobacterium Infections biology Interferon-alpha Middle Aged biology.organism_classification Child Preschool biology.protein Leukocytes Mononuclear Cytokines Nontuberculous mycobacteria Female Signal transduction Ex vivo medicine.drug Signal Transduction |
| Zdroj: | Journal of Clinical Immunology, 33(5), 991-1001. Springer New York |
| ISSN: | 1573-2592 0271-9142 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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