Anti-IFN-γ Autoantibodies and Disseminated Opportunistic Infections in Immunocompetent Indian Adults.

OBJECTIVES: Though anti-IFN-γ autoantibodies are associated with adult-onset immunodeficiency among Asians, they are not routinely tested. Despite rising reports of disseminated opportunistic infections in apparently immunocompetent individuals, the clinical course and prevalence of anti-IFN-γ autoantibodies remain poorly characterized. We evaluated the association between severe opportunistic infections and plasma anti-IFN-γ antibodies and IL-12 levels.

METHODS: This cross-sectional study evaluated levels of anti-IFN-γ autoantibodies and IL-12 in HIV negative, apparently immunocompetent patients with disseminated intracellular opportunistic infections (Group 1; n=44) or persistent tuberculosis (Group 2; n=41) against healthy controls (Group 3; n=34).

RESULTS: Common infections in Group 1 were disseminated non-tuberculous mycobacterial infections (40·9%), cryptococcosis (36·4%), and disseminated histoplasmosis (13·6%). Median anti-IFN-γ autoantibody concentrations were significantly higher in Group 1 [66·02 ng/mL; IQR 52·19-85·86; p = 0·004] and Group 2 [65·46 ng/mL; IQR 52·31-86·03; p = 0·004] than in Group 3 [44·77 ng/mL; IQR 28·56-69·93]. When compared to controls, IL-12 levels were significantly elevated in Group 1 (p = 0·006). In Group 1, three patients had relapses (6·8%), and three patients died (6·8%).

CONCLUSIONS: Patients with disseminated intracellular opportunistic infections and those with persistent tuberculosis had significantly higher levels of anti- IFN-γ autoantibodies than healthy controls . IL-12 levels were significantly higher in patients with disseminated intracellular opportunistic infections than among healthy controls. There was no significant difference in IL-12 levels among patients with persistent tuberculosis and healthy controls.