Title : Anti-IFN-? autoantibody syndrome presenting with disseminated NTM infections: A case series and therapeutic implications and review of literature
Abstract:
Anticytokine autoantibodies, particularly anti-IFN-γ autoantibodies (AAbs), disrupt cytokine functions, leading to infections, autoimmune-like diseases, and conditions resembling IL-12/IFN-γ pathway defects. Advances in genetic testing have clarified overlaps between autoinflammatory, autoimmune disorders, and primary immunodeficiencies but reveal complex phenotypes and pathways. While these insights deepen our understanding of immune mechanisms, they also complicate diagnosis and treatment, with limited options for IFN-γ deficiencies caused by genetic mutations. The adult-onset immunodeficiency with disseminated lymphadenitis due to nontuberculous mycobacteria (NTM) and other opportunistic infections, linked to high levels of anti–IFN-γ autoantibodies. This syndrome, initially identified in HIV-negative Asian patients, frequently affects individuals of Asian descent and may be associated with specific HLA alleles. The presence of neutralizing anti–IFN-γ autoantibodies impairs the IFN-γ–dependent immune response, likely contributing to the persistent NTM infection. This understanding of immunopathology underscores the potential for late-onset anti-IFN-γ autoantibody syndrome to manifest with disseminated NTM infections and highlights the timely diagnosis and prescribing rituximab as a potential therapeutic option
