Here, we demonstrate that anti-IFN-γ IgG was significantly elevated in SLE patients with severe infections, and could be a potential biomarker to predict the risk of severe infections in SLE patients. Further functional experiments revealed that anti-IFN-γ IgG directly neutralized IFN-γ and inhibited IFN-γ-induced STAT1 phosphorylation, which might explain the susceptibility to infection in some SLE patients. Here, STAT1 is linked to infection.