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

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 th...

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Main Authors: Zahra Hamidi Esfahani, Reza Yazdani, Sepideh Shahkarami, Fateme Babaha, Hassan Abolhassani, Maryam Sadr, Ali Akbar Pourfathollah, Asghar Aghamohammadi
Format: Article
Language:English
Published: Tehran University of Medical Sciences 2021-12-01
Series:Iranian Journal of Allergy, Asthma and Immunology
Subjects:
Online Access:https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3172
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author Zahra Hamidi Esfahani
Reza Yazdani
Sepideh Shahkarami
Fateme Babaha
Hassan Abolhassani
Maryam Sadr
Ali Akbar Pourfathollah
Asghar Aghamohammadi
author_facet Zahra Hamidi Esfahani
Reza Yazdani
Sepideh Shahkarami
Fateme Babaha
Hassan Abolhassani
Maryam Sadr
Ali Akbar Pourfathollah
Asghar Aghamohammadi
author_sort Zahra Hamidi Esfahani
collection DOAJ
description 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.
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spelling doaj.art-6cfbbfef2b4a4197a7ba1405fef2397f2022-12-21T21:11:24ZengTehran University of Medical SciencesIranian Journal of Allergy, Asthma and Immunology1735-15021735-52492021-12-0120610.18502/ijaai.v20i6.8021Evaluation of MicroRNA-125b-5p and Transcription Factors BLIMP1 and IRF4 Expression in Unsolved Common Variable Immunodeficiency PatientsZahra Hamidi Esfahani0Reza Yazdani1Sepideh Shahkarami2Fateme Babaha3Hassan Abolhassani4Maryam Sadr5Ali Akbar Pourfathollah6Asghar Aghamohammadi7Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran AND Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, IranResearch Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, IranResearch Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran AND Department of Pediatrics, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany AND Medical Genetics Network (Megene), Universal Scientific Education and Research Network (USERN), Tehran, IranDepartment of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran AND Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, IranResearch Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran AND Department of Laboratory Medicine, Division of Clinical Immunology, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden AND Department of Biosciences and Nutrition, Division of Clinical Immunology, Karolinska Institute, Huddinge, SwedenMolecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, IranDepartment of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranResearch Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, IranCommon 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.https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3172Common Variable ImmunodeficiencyEpigenesisMicroRNAsPrimary immunodeficiency diseases;
spellingShingle Zahra Hamidi Esfahani
Reza Yazdani
Sepideh Shahkarami
Fateme Babaha
Hassan Abolhassani
Maryam Sadr
Ali Akbar Pourfathollah
Asghar Aghamohammadi
Evaluation of MicroRNA-125b-5p and Transcription Factors BLIMP1 and IRF4 Expression in Unsolved Common Variable Immunodeficiency Patients
Iranian Journal of Allergy, Asthma and Immunology
Common Variable Immunodeficiency
Epigenesis
MicroRNAs
Primary immunodeficiency diseases;
title Evaluation of MicroRNA-125b-5p and Transcription Factors BLIMP1 and IRF4 Expression in Unsolved Common Variable Immunodeficiency Patients
title_full Evaluation of MicroRNA-125b-5p and Transcription Factors BLIMP1 and IRF4 Expression in Unsolved Common Variable Immunodeficiency Patients
title_fullStr Evaluation of MicroRNA-125b-5p and Transcription Factors BLIMP1 and IRF4 Expression in Unsolved Common Variable Immunodeficiency Patients
title_full_unstemmed Evaluation of MicroRNA-125b-5p and Transcription Factors BLIMP1 and IRF4 Expression in Unsolved Common Variable Immunodeficiency Patients
title_short Evaluation of MicroRNA-125b-5p and Transcription Factors BLIMP1 and IRF4 Expression in Unsolved Common Variable Immunodeficiency Patients
title_sort evaluation of microrna 125b 5p and transcription factors blimp1 and irf4 expression in unsolved common variable immunodeficiency patients
topic Common Variable Immunodeficiency
Epigenesis
MicroRNAs
Primary immunodeficiency diseases;
url https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3172
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