Sequential Talaromyces marneffei and Legionella pneumophila infections leading to the diagnosis of anti–interferon-γ autoantibody–associated immunodeficiency: a case report

Opportunistic infections caused by uncommon intracellular pathogens can serve as important clues to underlying immune dysfunction. We report a 57-year-old male who presented with chronic cough, dyspnea, fever, and weight loss. Chest imaging revealed diffuse pulmonary infiltrates and mediastinal lymphadenopathy, mimicking tuberculosis or lymphoma. Despite empirical anti-tuberculosis and broad-spectrum antibiotic therapy, his condition deteriorated. Metagenomic next-generation sequencing (mNGS) and culture confirmed Talaromyces marneffei infection. During antifungal therapy, he developed Legionella pneumophila pneumonia—an unusual sequential infection that raised suspicion of an immune defect. Comprehensive immunological evaluation revealed anti–interferon-γ (anti–IFN-γ) autoantibodies, supporting the diagnosis of AIGA-associated immunodeficiency. The patient had also shown repeatedly indeterminate interferon-γ release assay (IGRA) results, retrospectively suggesting impairment of the IFN-γ pathway. This case illustrates that recurrent or sequential infections with intracellular pathogens, particularly Talaromyces marneffei and Legionella pneumophila, should prompt evaluation for cell-mediated immunodeficiency such as AIGA syndrome. Early recognition may facilitate tailored antimicrobial therapy, immunological follow-up, and consideration of immunomodulatory treatment in selected patients.