Clinical findings of Talaromyces marneffei infection among patients with anti-interferon-γ immunodeficiency: a prospective cohort study

Abstract

Background: Talaromyces marneffei (T. marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. marneffei infection in southern China.Methods: Between January 2018 and September 2020, we enrolled patients aged 18 years or older who were HIV-negative. Patients were further stratified into four main groups: patients with T. marneffei infection (group 1, n=42), including anti-IFN-γ autoantibody-positive (group 1P) and anti-IFN-γ autoantibody-negative (group 1N) patients; patients with NTM infection (group 2, n=20); patients with pulmonary cryptococcosis (group 3, n=20); and healthy controls (group 4, n=40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded.Results: High anti-IFN-γ autoantibody titers were found in both groups 1 and 2. Compared with anti-IFN-γ autoantibody-negative patients with T. marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. However, the anti-IFN-γ autoantibody level did not correlate with the clinical disease course. Most of these patients had poor outcomes despite standardized antimicrobial therapy.Conclusion: T. marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions.