Central nervous system infections in patients with anti-interferon-γ autoantibodies: case series and review of the literature.

Background: Recently, increased reports reveal that anti-interferon-gamma (IFN-γ) autoantibodies (AIGAs) are strongly associated with several severe disseminated infections. However, reports on AIGAs with central nervous system (CNS) infections are rare. Here, we described three AIGAs-positive adults who had persistent or recurrent disseminated infections caused by Talaromyces marneffei (TM), nontuberculous mycobacteria (NTM), mycobacterium tuberculosis (TB), or other pathogens, accompanied with CNS infections. In addition, we conducted a thorough literature review of AIGAs-positive patients with CNS infections.

Case presentation: We report three HIV-negative cases of recurrent disseminated infections including CNS, and AIGAs were measured. All patients had no history of underlying diseases or immunosuppression and presented with fever, cough, and headache. They were negative for HIV antibodies but positive for AIGAs. The patients were diagnosed with CNS infections based on cerebrospinal fluid (CSF) examination and next-generation sequencing (NGS). All patients received anti-infective treatment according to different pathogens, and their condition remained stable without recurrence.

Conclusions: In adults with severe and recurrent infections of multiple organs without known immunodeficiency, adult-onset immunodeficiency (AOID) associated with AIGAs should be considered. In AIGAs-positive patients, the blood-brain barrier (BBB) may be disrupted, leading to susceptibility to CNS infections.