Case Report: From Talaromyces marneffei infection to EBV-positive lymphoma in an adult with anti-IFN-γ autoantibody-associated immunodeficiency.

BACKGROUND

Anti-interferon-γ autoantibodies (AIGAs) are an established cause of adult-onset immunodeficiency (AOID), predisposing individuals to disseminated intracellular infections such as Talaromyces marneffei (TM). However, their role in promoting persistent immune dysregulation and subsequent lymphomagenesis remains poorly understood.

CASE PRESENTATION: A 63-year-old Chinese female with high-titer AIGAs (1:2500) initially presented with disseminated TM. Despite antifungal therapy, her clinical course was complicated by recurrent opportunistic infections-including Varicella-zoster virus (VZV) and Mycobacterium persicum (M. persicum), and steroid-dependent inflammatory episodes. Approximately two years after the initial presentation, she developed an Epstein-Barr virus (EBV)-positive aggressive B-cell lymphoma, confirmed by mass biopsy and PET/CT. Despite treatment with rituximab and broad-spectrum antimicrobials, she died of Gram-negative septic shock. Whole-exome sequencing (WES) revealed a CREBBP p.Q278P mutation, providing a genetic perspective on her disease susceptibility.

CONCLUSION

This case illustrates a rare progression from AIGAs-associated immunodeficiency to EBV-driven lymphoma, suggesting a "triple-hit" pathogenic model that warrants further investigation, comprising: (1) AIGAs-associated AOID; (2) chronic antigenic stimulation from persistent infections that may exacerbate immune dysregulation; and (3) a CREBBP mutation that may act as a genetic contributor to malignant transformation. This case underscores the necessity for rigorous tumor surveillance and individualized treatment in patients with AIGAs-associated immunodeficiency.