title: Anti-IFN-gamma autoantibodies in disseminated nontuberculous mycobacterial infections.
abstract: Although many patients with disseminated nontuberculous mycobacterial disease have molecular defects in the IFN-gamma/IL-12 axis, recent case reports have shown autoantibodies against IFN-gamma associated with severe nontuberculous mycobacterial infections. To check this finding in an independent population, we screened 35 patients with either disseminated or pulmonary nontuberculous mycobacterial infections for whom no molecular defect was known. We identified high-titer-neutralizing anti-IFN-gamma IgG in the plasma of six patients. All six patients were female, parous, of East Asian descent, and had disseminated infection, predominantly with rapidly growing mycobacteria. The anti-IFN-gamma IgG had in vitro biological activity on the IFN-gamma-dependent phosphorylation of STAT-1 as well as on the IFN-gamma-dependent up-regulation of TNF-alpha and IL-12. In contrast, this anti-IFN-gamma Ab had no effect on IFN-alpha-dependent STAT-1 phosphorylation. These patients confirm a novel syndrome linking autoimmunity and immunodeficiency.
authors.affiliation: Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1684, USA.
authors.forename: Smita Y
authors.initials: SY
authors.lastname: Patel
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Brown
authors.forename: Larry
authors.initials: L
authors.lastname: Lantz
authors.forename: Ted
authors.initials: T
authors.lastname: Gay
authors.forename: Stuart
authors.initials: S
authors.lastname: Cohen
authors.forename: Lenna A
authors.initials: LA
authors.lastname: Martyak
authors.forename: Bernard
authors.initials: B
authors.lastname: Kubak
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D017099:IgG Deficiency / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D009164:Mycobacterium Infections / Q000276:immunology*; D010766:Phosphorylation; D013577:Syndrome
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D007371:Interferon-gamma