# MicroRNA Deregulation and Immune Checkpoint Interactions in Common Variable Immunodeficiency and CLL-Associated Secondary Immunodeficiency

## TL;DR

This study explores how microRNA levels differ in people with certain immune disorders and cancer-related immunodeficiency, suggesting they could help diagnose and monitor these conditions.

## Contribution

The study identifies specific microRNA expression patterns in CVID and CLL-associated SID, linking them to immune checkpoint regulation and potential biomarker utility.

## Key findings

- Reduced miR-16, miR-30c, miR-181a, miR-29a, miR-150, and miR-326 levels in CVID suggest impaired immune regulation.
- Elevated miR-21, miR-125b, and miR-155 in CLL with SID indicate roles in tumor growth and immunosuppression.
- Correlations between miRNA levels and immune checkpoints suggest a complex regulatory network in immune dysregulation.

## Abstract

Background: Immunodeficiencies are a heterogeneous group of disorders classified etiologically as primary (congenital) or secondary (acquired). Primary immunodeficiencies (PIDs), such as common variable immunodeficiency (CVID), result from genetic mutations that impair the development and function of lymphocytes. Secondary immunodeficiencies (SIDs) arise as a consequence of chronic diseases, lymphoid malignancies, or immunosuppressive therapies. Aim of the study: The purpose of this study was to assess the serum expression profile of selected microRNAs (miRNAs) in patients with CVID and in those with chronic lymphocytic leukemia (CLL) and coexisting SID, compared to healthy individuals. Methods: Digital PCR (dPCR) was applied to quantify the serum expression levels of selected miRNAs in patients with CVID, patients with CLL and SID, and in healthy controls. Results: dPCR revealed significantly reduced levels of miR-16, miR-30c, miR-181a, miR-29a, miR-150, and miR-326 in the CVID group, potentially reflecting impaired regulatory mechanisms of the immune system. In contrast, elevated levels of miR-21, miR-125b, and miR-155 were observed in the CLL group with SID, suggesting their role in tumorigenesis and secondary immunosuppression. Correlations between miRNA levels and the expression of immune checkpoints (PD-1, CTLA-4, CD200) indicated the involvement of a complex regulatory network encompassing both humoral and cellular immune mechanisms. Conclusions: The results provide preliminary evidence that selected miRNAs could reflect disease-specific immune dysregulation patterns and may hold potential as diagnostic and prognostic biomarkers in both PIDs and SIDs.