title: Anti-CD20 (rituximab) therapy for anti-IFN-γ autoantibody-associated nontuberculous mycobacterial infection.
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.
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. brownesa@niaid.nih.gov
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Browne
authors.forename: Rifat
authors.initials: R
authors.lastname: Zaman
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Sampaio
authors.forename: Kamonwan
authors.initials: K
authors.lastname: Jutivorakool
authors.forename: Lindsey B
authors.initials: LB
authors.lastname: Rosen
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Minjal J
authors.initials: MJ
authors.lastname: Pancholi
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Yang
authors.forename: Debra Long
authors.initials: DL
authors.lastname: Priel
authors.forename: Gulbu
authors.initials: G
authors.lastname: Uzel
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Freeman
authors.forename: Carlton E
authors.initials: CE
authors.lastname: Hayes
authors.forename: Roger
authors.initials: R
authors.lastname: Baxter
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Cohen
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D008875:Middle Aged; D009164:Mycobacterium Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000069283:Rituximab; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007155:Immunologic Factors; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000069283:Rituximab; D007371:Interferon-gamma