Anti-IFN-? autoantibody syndrome presenting with disseminated NTM infections: A case series and therapeutic implications and review of literature

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

Biography:

Dr. Yazdan Mirzanejad is a Clinical Professor in the Division of Infectious Diseases at the University of British Columbia (UBC) and a staff physician in Infectious Diseases and Tropical Medicine at Surrey Memorial Hospital. With more than 28 years of experience, he has dedicated his career to clinical care, medical education, and mentorship in infectious diseases and tropical medicine. Since 2014, he has served as Site Lead for the ambulatory teaching curriculum at UBC’s Surrey Campus, supporting undergraduate and postgraduate education, learner development, and faculty mentorship.

His academic interests include tropical medicine, antimicrobial resistance and stewardship, severe infections and sepsis, emerging pathogens, and the health impacts of climate change through a One Health perspective. His research has contributed to studies on septic shock, diabetic foot infections, Lyme carditis, Cryptococcus gattii, extensively drug-resistant Salmonella Typhi, and national antimicrobial surveillance initiatives. Recognized repeatedly for excellence in clinical teaching, Dr. Mirzanejad integrates clinical reasoning, microbiology, public health, and global medicine into his educational approach, emphasizing patient-centred care, practical decision-making, and collaboration across diverse healthcare settings.