Abstract
Patients with anti-IFN-γ autoantibodies have impaired IFN-γ signaling, leading to severe disseminated infections with intracellular pathogens, especially nontuberculous mycobacteria. Disease may be severe and progressive, despite aggressive treatment. To address the underlying pathogenic IFN-γ autoantibodies we used the therapeutic monoclonal rituximab (anti-CD20) to target patient B cells. All subjects received between 8 and 12 doses of rituximab within the first year to maintain disease remission. Subsequent doses were given for relapsed infection. We report 4 patients with refractory disease treated with rituximab who had clinical and laboratory evidence of therapeutic response as determined by clearance of infection, resolution of inflammation, reduction of anti-IFN-γ autoantibody levels, and improved IFN-γ signaling.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Aged
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Antibodies, Monoclonal, Murine-Derived / therapeutic use*
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Autoantibodies / immunology*
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B-Lymphocytes / immunology*
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Blotting, Western
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Female
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Flow Cytometry
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Humans
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Immunologic Factors / therapeutic use*
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Interferon-gamma / immunology*
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Interferon-gamma / pharmacology
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Middle Aged
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Mycobacterium Infections / drug therapy*
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Mycobacterium Infections / immunology
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Mycobacterium Infections / microbiology
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Mycobacterium Infections, Nontuberculous / immunology*
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Phosphorylation
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Rituximab
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STAT1 Transcription Factor / genetics
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STAT1 Transcription Factor / metabolism
Substances
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Antibodies, Monoclonal, Murine-Derived
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Autoantibodies
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Immunologic Factors
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RNA, Messenger
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STAT1 Transcription Factor
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STAT1 protein, human
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Rituximab
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Interferon-gamma