Anti-IFN-gamma autoantibodies in disseminated nontuberculous mycobacterial infections

Abstract

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