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Article

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

by
Paulina Mertowska
1,*,
Sebastian Mertowski
1,
Milena Czosnek
2,
Barbara Sosnowska-Pasiarska
3,
Aleksandra Krasińska-Płachta
4,
Zbigniew Krasiński
5,
Tomasz Urbanowicz
6,
Krzysztof Bojarski
7,
Mansur Rahnama-Hezavah
8 and
Ewelina Grywalska
1
1
Department of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland
2
Student Research Group of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland
3
Department of Oncocardiology, Holy Cross Cancer Center, 25-734 Kielce, Poland
4
Department of Ophthalmology, Poznan University of Medical Sciences, Fredry 10, 61-107 Poznan, Poland
5
Department of Vascular, Endovascular Surgery, Angiology and Phlebology, Poznan University of Medical Science, Dluga 1/2, 61-848 Poznań, Poland
6
Department of Cardiac Surgery and Transplantology, Poznan University of Medical Sciences, 61-848 Poznań, Poland
7
General Surgery Department, SP ZOZ in Leczna, 52 Krasnystawska Street, 21-010 Leczna, Poland
8
Department of Dental Surgery, Medical University of Lublin, 6 Chodźki Street, 20-093 Lublin, Poland
*
Author to whom correspondence should be addressed.
Cells 2025, 14(20), 1577; https://doi.org/10.3390/cells14201577
Submission received: 6 September 2025 / Revised: 6 October 2025 / Accepted: 7 October 2025 / Published: 10 October 2025
(This article belongs to the Special Issue MicroRNAs: Regulators of Cellular Fate)

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.
Keywords: immunodeficiencies; CVID; CLL; microRNA; dPCR; immune checkpoints; biomarkers immunodeficiencies; CVID; CLL; microRNA; dPCR; immune checkpoints; biomarkers

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MDPI and ACS Style

Mertowska, P.; Mertowski, S.; Czosnek, M.; Sosnowska-Pasiarska, B.; Krasińska-Płachta, A.; Krasiński, Z.; Urbanowicz, T.; Bojarski, K.; Rahnama-Hezavah, M.; Grywalska, E. MicroRNA Deregulation and Immune Checkpoint Interactions in Common Variable Immunodeficiency and CLL-Associated Secondary Immunodeficiency. Cells 2025, 14, 1577. https://doi.org/10.3390/cells14201577

AMA Style

Mertowska P, Mertowski S, Czosnek M, Sosnowska-Pasiarska B, Krasińska-Płachta A, Krasiński Z, Urbanowicz T, Bojarski K, Rahnama-Hezavah M, Grywalska E. MicroRNA Deregulation and Immune Checkpoint Interactions in Common Variable Immunodeficiency and CLL-Associated Secondary Immunodeficiency. Cells. 2025; 14(20):1577. https://doi.org/10.3390/cells14201577

Chicago/Turabian Style

Mertowska, Paulina, Sebastian Mertowski, Milena Czosnek, Barbara Sosnowska-Pasiarska, Aleksandra Krasińska-Płachta, Zbigniew Krasiński, Tomasz Urbanowicz, Krzysztof Bojarski, Mansur Rahnama-Hezavah, and Ewelina Grywalska. 2025. "MicroRNA Deregulation and Immune Checkpoint Interactions in Common Variable Immunodeficiency and CLL-Associated Secondary Immunodeficiency" Cells 14, no. 20: 1577. https://doi.org/10.3390/cells14201577

APA Style

Mertowska, P., Mertowski, S., Czosnek, M., Sosnowska-Pasiarska, B., Krasińska-Płachta, A., Krasiński, Z., Urbanowicz, T., Bojarski, K., Rahnama-Hezavah, M., & Grywalska, E. (2025). MicroRNA Deregulation and Immune Checkpoint Interactions in Common Variable Immunodeficiency and CLL-Associated Secondary Immunodeficiency. Cells, 14(20), 1577. https://doi.org/10.3390/cells14201577

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