Anti-IFN-γ autoantibodies in disseminated nontuberculous mycobacterial infections

Smita Y. Patel, Li Ding, Margaret R. Brown, Larry Lantz, Ted Gay, Stuart H Cohen, Lenna A. Martyak, Bernard Kubak, Steven M. Holland

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124 Scopus citations

Abstract

Although many patients with disseminated nontuberculous mycobacterial disease have molecular defects in the IFN-γ/IL-12 axis, recent case reports have shown autoantibodies against IFN-γ 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-γ 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-γ IgG had in vitro biological activity on the IFN-γ-dependent phosphorylation of STAT-1 as well as on the IFN-γ-dependent up-regulation of TNF-α and DL-12. In contrast, this anti-IFN-γ Ab had no effect on IFN-α-dependent STAT-1 phosphorylation. These patients confirm a novel syndrome linking autoimmunity and immunodeficiency.

Original languageEnglish (US)
Pages (from-to)4769-4776
Number of pages8
JournalJournal of Immunology
Volume175
Issue number7
StatePublished - Oct 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Patel, S. Y., Ding, L., Brown, M. R., Lantz, L., Gay, T., Cohen, S. H., Martyak, L. A., Kubak, B., & Holland, S. M. (2005). Anti-IFN-γ autoantibodies in disseminated nontuberculous mycobacterial infections. Journal of Immunology, 175(7), 4769-4776.