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

BACKGROUND: Opportunistic infections caused by uncommon intracellular pathogens can serve as important clues to underlying immune dysfunction. CASE PRESENTATION: 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. CONCLUSIONS: 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.