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Introduction: Anti-interferon-γ (IFNγ) autoantibodies have been associated with disseminated mycobacterial infections, mostly in patients from Southeast Asia. Purpose: 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 IgG 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. [ABSTRACT FROM AUTHOR]