MicroRNA changes with macro potential contribute to secondary immunodeficiency in chronic lymphocytic leukemia during...

Chronic lymphocytic leukemia (CLL) is characterized by immune dysfunctions driven by miRNA deregulation and the activation of immune checkpoint pathways, which contribute to disease progression and secondary immunodeficiency (SID). This study examines the interplay between miRNA expression profiles, Epstein-Barr virus (EBV) reactivation, and immune checkpoint pathways in the context of small intestine disease (SID) development in chronic lymphocytic leukemia (CLL). Patients were stratified into groups based on the presence of SID and EBV reactivation. Comprehensive analyses included miRNA profiling, EBV infection markers, and the expression of PD-1, PD-L1, CTLA-4, CD200, and CD86 on CD4 + and CD8 + T cells, as well as CD19 + B cells. The results revealed significant suppression of tumor-suppressive miRNAs (e.g., miR-15a, miR-181a, and miR-29a) in the SID EBV + group, correlating with enhanced immunosuppression. The highest expression of exhaustion markers (PD-1, PD-L1, CTLA-4) and immunosuppressive molecules (CD200/CD200R) was observed in the SID EBV⁺ group compared to all other groups, including SID EBV⁻, which may reflect the enhanced mechanisms of immunosuppression and lymphocyte exhaustion accompanying EBV reactivation in the course of secondary immunodeficiencies. Correlation analyses underscored significant associations between miRNA levels, EBV reactivation markers, and immune checkpoint activation. These findings highlight the dual role of miRNA deregulation and immune checkpoint activation in the immunosuppressive microenvironment of CLL. The study underscores the diagnostic and therapeutic potential of miRNAs and immune checkpoints in managing SID and EBV-associated immune dysregulation in CLL.