The first US domestic report of disseminated Mycobacterium avium complex and anti-interferon-γ autoantibodies

Abstract

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 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.

Fig. 1

Axial T1 weighted post-contrast magnetic resonance imaging of the brain reveals right frontal parenchymal enhancing mass with internal areas of T1 signal, surrounded by marked vasogenic edema causing local mass effect and leftward midline shift

Fig. 2

Identification and functional evaluation of anti-IFNγ autoantibodies. a Multiplex screen for anticytokine autoantibodies in our patient and normal control plasma (N=9). b Determination of IgG subclasses in patient plasma. c From left to right, normal PBMC incubated with normal and patient plasma or patient PBMC incubated with normal or patient plasma were left unstimulated or stimulated with IFNa or IFNg and evaluated for STAT-1 phosphorylation (pSTAT1). d Normal PBMC in the presence of normal and patient plasma were stimulated and supernatants collected for evaluation of IFNg-augmentation of LPS-induced TNFa and IL-12p70 and E. IL-12-augmentation of PHA-induced IFNγ production