Evaluation of MicroRNA-125b-5p and Transcription Factors BLIMP1 and IRF4 Expression in Unsolved Common Variable Immunodeficiency Patients

Zahra Hamidi Esfahani; Reza Yazdani; Sepideh Shahkarami; Fateme Babaha; Hassan  Abolhassani; Maryam Sadr; Ali Akbar Pourfathollah; Asghar Aghamohammadi

doi:10.18502/ijaai.v20i6.8021

Zahra Hamidi Esfahani Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Reza Yazdani Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Sepideh Shahkarami Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Fateme Babaha Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Hassan Abolhassani Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Maryam Sadr Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Ali Akbar Pourfathollah Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Asghar Aghamohammadi Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v20i6.8021

Keywords: Common variable immunodeficiency; Epigenesis; MicroRNAs; Primary immunodeficiency diseases

Abstract

Common variable immunodeficiency (CVID) is the most prevalent form of symptomatic primary humoral immunodeficiencies characterized by failure in the final differentiation of B lymphocytes. The majority of CVID cases have no identified genetic defect, and epigenetic alteration could be involved in the pathogenesis of CVID. Hence, we aimed to evaluate the expression of hsa-miR-125b-5p -and, B lymphocyte-induced maturation protein-1(BLIMP-1) and interferon regulatory protein-4 (IRF-4) in a group of CVID patients with no definitive genetic diagnosis in comparison with healthy individuals.

Ten CVID patients (all known genes excluded) and 10 age and sex-matched healthy controls participated in the study. B lymphocytes were isolated and expression of miR-125b-5p, IRF4, and BLIMP1 were evaluated by real-time polymerase chain reaction (RT-PCR). Moreover, B cell subsets were analyzed by flow cytometry.

The results showed that the relative expression of miR-125b-5p in CVID patients was increased while it was decreased for the BLIMP1 and IRF4 transcription factors compared with the healthy controls. Although a reduction was observed in switched and non-switched memory B cells among all high-miR patients, these subsets were decreased in patients with normal miR expression (71.0% and 85.0%, respectively).

Our results suggest that overexpression of miR-125b-5p affects the terminal differentiation of B cells in a selected group of CVID patients by downregulating the BLIMP-1 gene and more intensively for the IRF-4 gene expressions.