CREBBP and immunodeficiency disease: Whole-exome sequencing (WES) revealed a CREBBP p.Q278P mutation, providing a genetic perspective on her disease susceptibility.<h4>Conclusion</h4>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.