title: Interferon alpha treatment of patients with impaired interferon gamma signaling.
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.
authors.affiliation: Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, CRC B3-4233 MSC 1684, Bethesda, MD 20892-1684, USA.
authors.forename: H I
authors.initials: HI
authors.lastname: Bax
authors.forename: A F
authors.initials: AF
authors.lastname: Freeman
authors.forename: L
authors.initials: L
authors.lastname: Ding
authors.forename: A P
authors.initials: AP
authors.lastname: Hsu
authors.forename: B
authors.initials: B
authors.lastname: Marciano
authors.forename: E
authors.initials: E
authors.lastname: Kristosturyan
authors.forename: T
authors.initials: T
authors.lastname: Jancel
authors.forename: C
authors.initials: C
authors.lastname: Spalding
authors.forename: J
authors.initials: J
authors.lastname: Pechacek
authors.forename: K N
authors.initials: KN
authors.lastname: Olivier
authors.forename: L A
authors.initials: LA
authors.lastname: Barnhart
authors.forename: L
authors.initials: L
authors.lastname: Boris
authors.forename: C
authors.initials: C
authors.lastname: Frein
authors.forename: R J
authors.initials: RJ
authors.lastname: Claypool
authors.forename: V
authors.initials: V
authors.lastname: Anderson
authors.forename: C S
authors.initials: CS
authors.lastname: Zerbe
authors.forename: S M
authors.initials: SM
authors.lastname: Holland
authors.forename: E P
authors.initials: EP
authors.lastname: Sampaio
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000235:genetics / Q000378:metabolism; D009164:Mycobacterium Infections / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult; D000096743:Interferon gamma Receptor
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor