Severe Salmonella Infections in AIGAs Immunodeficiency Syndrome: Hyperinflammation and Immune Dysregulation

Anti-interferon-γ autoantibodies (AIGAs) immunodeficiency syndrome is a rare acquired disorder characterized by impaired IFN-γ signaling, predisposing patients to severe intracellular infections. While disseminated non-tuberculous mycobacteria (NTM) and Talaromyces marneffei (TM) are well-documented pathogens, the clinical and immunological features of Salmonella coinfection remain poorly characterized.

This retrospective study analyzed 12 HIV-negative patients with AIGAs-positive status and confirmed Salmonella infection at the First Affiliated Hospital of Guangxi Medical University, China (2021-2024). Data included demographics, clinical manifestations, laboratory findings, co-infections, treatment, and outcomes. AIGAs were detected via ELISA and Western blot, with neutralizing activity confirmed by STAT1 phosphorylation inhibition.

The cohort was predominantly composed of middle-aged males (83.3%, mean age 55.75 ±8.06 years). The most common symptoms were fever, fatigue and cough (each 91.7%), followed by poor appetite (83.3%), systemic symptoms (chills, weight loss; 58.3%) and dyspnea (58.3%). Bone or joint pain occurred in 41.7% and gastrointestinal complaints (abdominal pain, diarrhea or distension) in 25%. Five patients (41.7%) developed septic shock, three requiring vasopressors and two mechanical ventilations. All had high AIGAs titres (1:2500) and hyper-inflammation (median WBC17.3×10⁹/L, CRP138.1mg/dL, PCT1.28ng/mL). Bacteraemia was present in 91.7% and mortality was 16.7% (2/12). Polymicrobial co-infection was universal; notably cytomegalovirus (50%) and TM (25%). Immunological profiling showed hyperglobulinaemia (IgG23.5±10.6g/L) and elevated IgE (257.5[79.7-598.2]IU/mL). Despite broad-spectrum antibiotics (83.3% survival), both fatalities occurred in patients who had not undergone NGS-based diagnosis.

This study is the first to define AIGAs-associated Salmonella infection as a distinct clinical syndrome, characterized by severe bacteremia, paradoxical hyperinflammation, universal polymicrobial coinfections, and immune dysregulation. Our findings underscore the critical importance of comprehensive pathogen detection, particularly via NGS, for timely diagnosis and improved patient outcomes.