Clinical Cognition and Practice in Anti-Interferon-γ Autoantibody-Associated Immunodeficiency Syndrome

Adult-onset immunodeficiency syndrome mediated by anti-interferon-gamma autoantibody (AIGA) is a rare disorder that has garnered increasing recognition in recent years. The condition is most prevalent among adults in Southeast Asia. It is characterized by recurrent disseminated opportunistic infections, frequently involving multiple organ systems such as the lungs, lymph nodes, bones, and skin. The pathogenesis is primarily attributed to the presence of neutralizing AIGAs, which impair the IFN-γ-mediated JAK-STAT1 signaling pathway, leading to compromised host defense against intracellular pathogens. Laboratory diagnosis requires both quantification of AIGA titers and assessment of their neutralizing activity. Clinical diagnosis relies on a combination of characteristic manifestations, demonstrated immunologic dysfunction, and seropositivity for AIGAs. During the acute stage, management focuses on antimicrobial therapy, while during the stable stage, it can be categorized into three clinical subtypes: high AIGA titers with immune damage, high AIGA titers without immune damage, and low AIGA titers without immune damage. Among these, patients with high AIGA titers and immune damage require immunomodulatory strategies-such as glucocorticoids and rituximab-tailored to individual AIGA levels and immune status. Due to the current absence of unified clinical guidelines, this review synthesizes available evidence and clinical expertise to provide a comprehensive overview of the epidemiology, pathogenesis, clinical presentation, diagnostic criteria, and treatment approaches related to AIGA-mediated immunodeficiency. Our aim is to assist clinicians in the recognition and management of this syndrome and to facilitate further clinical research and guideline development.