The First US Domestic Report of Disseminated Mycobacterium avium Complex and Anti-Interferon-γ Autoantibodies

Elise O’Connell, Lindsey B. Rosen, Richard W. LaRue, Valeria Fabre, Michael T. Melia, Paul G. Auwaerter, Steven M. Holland, Sarah K. Browne

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)928-932
Number of pages5
JournalJournal of Clinical Immunology
Volume34
Issue number8
DOIs
StatePublished - Nov 5 2014

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Keywords

  • Anticytokine autoantibodies
  • interferon-gamma (IFNγ)
  • intracranial infection
  • nontuberculous mycobacteria

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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