Neutralizing anti-IFN-γ IgG was increased in patients with systemic lupus erythematosus and associated with susceptibility to infection

Objectives Systemic lupus erythematosus (SLE) is a complicated autoimmune disease, in which infection is a leading cause of death. Some SLE patients clinically presented with recurrent and refractory infections, which manifested as adult-onset immunodeficiency syndrome due to the production of anti-interferon-gamma (anti-IFN-gamma) autoantibodies. This study aimed to investigate the role of anti-IFN-gamma autoantibodies concerning severe infections in SLE patients. Methods We detected serum levels of anti-IFN-gamma IgG/IgM isotypes in SLE patients with severe infections (n = 55), SLE patients without severe infections (n = 120), rheumatoid arthritis (n = 24), ankylosing spondylitis (n = 24), and healthy controls (n = 60). The relationship between anti-IFN-gamma autoantibodies and clinical characteristics and laboratory parameters were analyzed. We further evaluated the neutralizing ability of anti-IFN-gamma IgG. Results The level of anti-IFN-gamma IgG was significantly elevated in SLE patients with severe infections compared with the other groups (all p < 0.01), and the positive rates of anti-IFN-gamma IgG in SLE patients with and without severe infections were 29.1% and 10.8%, respectively. Further analysis indicated that the levels of anti-IFN-gamma IgG were positively associated with the SLEDAI score (r = 0.6420, p < 0.001), and it could predict the susceptibility to severe infections in SLE patients. Moreover, the inhibition and function assay showed that purified IgG from anti-IFN-gamma IgG-positive SLE patients could neutralize IFN-gamma, and further impair IFN-gamma-induced STAT1 phosphorylation. Conclusions The neutralizing anti-IFN-gamma IgG might increase the susceptibility to infection in SLE patients, which has important implications for the treatment.

Automated summary

The role of anti-IFN-gamma autoantibodies in severe infections in SLE patients was investigated. The level of anti-IFN-gamma IgG was significantly elevated in SLE patients with severe infections, and it was positively associated with the SLEDAI score. The purified IgG from anti-IFN-gamma IgG-positive SLE patients could neutralize IFN-gamma and impair IFN-gamma-induced STAT1 phosphorylation.