title: The first US domestic report of disseminated Mycobacterium avium complex and anti-interferon-γ autoantibodies.
abstract: BACKGROUND
  Anti-interferon-γ (IFNγ) autoantibodies have been associated with disseminated mycobacterial infections, mostly in patients from Southeast Asia.
  
  
  OBJECTIVE
  We studied an American-born, Caucasian female with M. avium complex infection of the subglottic mucosa and brain for underlying etiologies of infection.
  
  
  METHODS
  Plasma was screened for anticytokine autoantibodies using a Luminex-based approach. The ability of patient plasma to block IFNγ-induced STAT1 phosphorylation in normal blood cells was evaluated by flow cytometry with intracellular staining. Plasma inhibition of IFNγ production and IFNγ-induced cytokines in normal and patient blood cells washed of autologous plasma was also evaluated.
  
  
  RESULTS
  Patient plasma contained high-titer IgG anti-IFNγ autoantibodies, primarily of the IgG1 subclass. Patient but not control plasma prevented IFNγ-induced STAT1 phosphorylation and expression of the IFNγ-inducible cytokines tumor necrosis factor (TNF) α and interleukin (IL)-12 in normal blood cells. Patient blood cells washed free of autologous plasma demonstrated normal IFNγ production and response.
  
  
  CONCLUSIONS
  Disseminated nontuberculous mycobacterial infections should always prompt immune evaluation. This first case of disseminated nontuberculous mycobacterial infection and anti-IFNγ autoantibodies in an American-born Caucasian suggests that anti-cytokine autoantibodies are not racially or regionally restricted.
authors.affiliation: Laboratory of Parasitic Diseases, NIAID, NIH, CRC B3-4141, MSC 1684, Bethesda, MD, 20892-1684, USA.
authors.forename: Elise
authors.initials: E
authors.lastname: O'Connell
authors.forename: Lindsey B
authors.initials: LB
authors.lastname: Rosen
authors.forename: Richard W
authors.initials: RW
authors.lastname: LaRue
authors.forename: Valeria
authors.initials: V
authors.lastname: Fabre
authors.forename: Michael T
authors.initials: MT
authors.lastname: Melia
authors.forename: Paul G
authors.initials: PG
authors.lastname: Auwaerter
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Browne
mesh_terms: D000328:Adult; D001249:Asthma / Q000150:complications; D001323:Autoantibodies / Q000097:blood*; D001921:Brain / Q000473:pathology; D004417:Dyspnea / Q000150:complications; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008279:Magnetic Resonance Imaging; D015269:Mycobacterium avium Complex; D015270:Mycobacterium avium-intracellulare Infection / Q000150:complications / Q000175:diagnosis / Q000276:immunology*; D012907:Smoking; D014481:United States; D044465:White People
chemical_list: D001323:Autoantibodies; D007371:Interferon-gamma