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

2021 ◽  
Author(s):  
Zahra Hamidi Esfahani ◽  
Reza Yazdani ◽  
Sepideh Shahkarami ◽  
Fateme Babaha ◽  
Hassan Abolhassani ◽  
...  
Keyword(s):  
Transcription Factors ◽  
B Cells ◽  
B Lymphocytes ◽  
Common Variable Immunodeficiency ◽  
Regulatory Protein ◽  
Genetic Defect ◽  
Genetic Diagnosis ◽  
Healthy Controls ◽  
Gene Expressions ◽  
Common Variable

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.  

scholarly journals Increased Expression of B Lymphocyte Induced Maturation Protein 1 (BLIMP1) in Patients with Common Variable Immunodeficiency (CVID)

2020 ◽  
Author(s):  
Shockrollah Farrokhi ◽  
Faezeh Abbasi-rad ◽  
Nafiseh Esmaeil ◽  
Roya Sherkat ◽  
Reza Yazdani ◽  
...  
Keyword(s):  
B Cells ◽  
Protein Expression ◽  
B Cell ◽  
Common Variable Immunodeficiency ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Healthy Controls ◽  
Maturation Protein ◽  
Mrna And Protein Expression ◽  
Common Variable

Common variable immunodeficiency (CVID) is a primary immune deficiency disorder characterized by a failure in B cell differentiation, impaired immunoglobulin production, and defect in response to vaccines. As a result of defective B cell maturation and differentiation in CVID, the affected patients commonly present with reduced numbers of memory B cell and antibody-secreting plasma cells. B-cell lymphoma 6 protein (BCL6) and B lymphocyte induced maturation protein 1 (BLIMP1) molecules are two important transcription factors that have key roles in the maturation of B cells to plasma cells. Hence, in the current survey, we aimed to evaluate the mRNA and protein expression levels of BCL6 and BLIMP1 in B lymphocytes isolated from peripheral blood in CVID patients. We collected blood samples from 12 CVID patients and 12 healthy controls. We isolated peripheral blood mononuclear cells (PBMCs) using Ficoll density gradient separation. Then, CD19+ B cells were purified using MACS. The protein expression and transcriptional level of BCL6 and BLIMP1 were respectively measured using flow cytometry and real-time PCR. Our results showed that the BLIMP1 mRNA expression, as well as BLIMP1 protein expression, were significantly higher in CVID patients compared to control subjects (p=0.009 and p=0.007, respectively). However, we found no significant difference in mRNA and protein expression of BCL6 between patients and healthy controls. According to our findings, increased mRNA and protein expression levels of BLIMP1 could be involved in defective maturation of B cells in patients with CVID and elucidate mechanistic insights into the pathogenesis of this disorder.

scholarly journals Immunophenotypic Analysis of B Lymphocytes in Patients with Common Variable Immunodeficiency: Identification of CD23 as a Useful Marker in the Definition of the Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Giuseppe Patuzzo ◽  
Filippo Mazzi ◽  
Antonio Vella ◽  
Riccardo Ortolani ◽  
Alessandro Barbieri ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
B Lymphocytes ◽  
Clinical Features ◽  
Common Variable Immunodeficiency ◽  
The Novel ◽  
Cell Surface Molecules ◽  
Surface Molecules ◽  
Definition Of ◽  
Common Variable

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by the failure of B lymphocytes differentiation leading to deficient immunoglobulins secretion. The identified genetic defects account only for a minority of cases. The importance of B cells immunophenotyping in the classification of CVID is known. This procedure can identify alterations on the cell surface molecules expression that could explain some immunological disorders characteristic of CVID. Moreover, some immunophenotypical aspects can correlate with clinical features of the disease. We used this procedure to analyze a cohort of 23 patients affected by CVID, in order to identify the novel alterations of B cells and to find the possible correlations with clinical features. Circulating B cells were studied by flow cytometry incubating whole blood with specific antibodies for B cell surface molecules including CD27, IgM, IgD, CD21, and CD23. We compared the population of “switched memory” IgD− CD27+ B lymphocytes with the population of “switched memory” IgM− IgD− CD23− CD27+ B cells. These last B cells were reduced in patients compared to healthy controls; moreover, IgM− IgD− CD23− CD27+ B cells were lower than IgD− CD27+ B cells in patients with CVID. The reduction of this subset of B lymphocytes correlates more tightly than IgD− CD27+ B cells with lymphadenopathy and airways infections. In conclusion, our findings may help in better identifying patients with CVID.

scholarly journals Investigating the Variation of TREC/KREC in Combined Immunodeficiencies

2021 ◽  
Author(s):  
Leila Shakerian ◽  
Maryam Nourizadeh ◽  
Mohsen Badalzadeh ◽  
Mohammad Reza Fazlollahi ◽  
Raheleh Shokouhi Shoormasti ◽  
...  
Keyword(s):  
B Cell ◽  
Common Variable Immunodeficiency ◽  
Positive Family History ◽  
Genetic Diagnosis ◽  
Genetic Defects ◽  
Healthy Controls ◽  
Significant Difference ◽  
Dock8 Deficiency ◽  
Excision Circles ◽  
Common Variable

T-cell receptor excision circles (TREC)/Kappa-deleting recombination excision circles (KREC) assay has been recently recognized for detecting patients with primary (T- and/or B-cell) immunodeficiency (PID). We aimed to investigate the alterations of these biomarkers in some combined immunodeficiency patients compared to the healthy controls in different age groups. TREC and KREC were assessed in a total of 82 PID patients, most of them with exact genetic diagnosis (3 months to 42 years); using quantitative real-time-polymerase chain reaction (PCR). Patients had a final diagnosis of common variable immunodeficiency (n=23), ataxia-telangiectasia (AT) (n=17), hyper-IgE syndrome (HIES) (7 with DOCK8 deficiency, 4 with signal transducer and activator of transcription 3 (STAT3) deficiency, and 8 children with unknown genetic defects), Wiskott-Aldrich syndrome (WAS) (n=20), purine nucleoside phosphorylase (PNP)deficiency(n=1), dedicator of cytokinesis2 (DOCK2) deficiency (n=1), recombinase activating gene1 (RAG1) deficiency (n=1). Very low to zero amounts of TREC and/or KREC were detected in 14 out of 23 cases of common variable immunodeficiency (CVID), 14 out of 17 cases of AT, 8 out of 20 cases of WAS, 6 out of 7 cases of DOCK8-deficiency patients, 4 out of 8 cases of HIES with unknown genetic defects and all patients with defects in DOCK2, PNP, and RAG1. STAT3-deficient patients were normal for both biomarkers. All patients showed a significant difference in both markers compared to age-matched healthy controls. Our findings highlight that apart from severe types of T/B cell defects, this assay can also be used for early diagnosis the patients with late-onset of disease and even PIDs without a positive family history.

scholarly journals Oxidative stress in common variable immunodeficiency

2021 ◽  
Vol 19 ◽  
pp. 205873922110024
Author(s):  
Sevgen Tanir Basaranoglu ◽  
Sukru Cekic ◽  
Emine Kirhan ◽  
Melahat Dirican ◽  
Sara S. Kilic
Keyword(s):  
Oxidative Stress ◽  
Common Variable Immunodeficiency ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Infectious Complications ◽  
Clinical Syndrome ◽  
University Hospital ◽  
Unknown Etiology ◽  
Healthy Controls ◽  
Oxidative Stress Biomarkers ◽  
Common Variable

Common variable immunodeficiency (CVID) is a heterogenous group of immunologic disorders of unknown etiology. Alterations of the normal cellular balance due to an increase in reactive oxygen species and/or decrease in antioxidant defense may lead to increased oxidative stress. We aimed to evaluate the levels of oxidative stress biomarkers in patients with CVID who had different presentations. We investigated the serum catalase (CAT), erythrocyte superoxide dismutase (SOD), erythrocyte reduced glutathione as antioxidants and serum malondialdehyde levels as lipid peroxidation marker in patients with CVID in Uludag University Hospital Department of Pediatric Allergy and Immunology’s outpatient clinics. In the analysis, there were 21 patients and 27 matched healthy controls. The median levels of CAT in patients with CVID was significantly lower than in healthy controls ( p = 0.04). Among the patients with CVID, 19% had autoimmune disease, one had Sjögren’s syndrome, one had autoimmune alopecia, one had juvenile rheumatoid arthritis, and one had chronic inflammatory demyelinating polyneuropathy. Patients with autoimmune complications had significantly lower CAT levels compared to the ones without autoimmune diseases ( p = 0.03). The patients without non-infectious complications (NICs) had lower SOD levels than the patients with NICs ( p = 0.05). The analysis of oxidative stress markers in the patients with CVID suggested a series of abnormalities in the anti-oxidant system. The clinical syndrome associations may be a useful tool for future studies to set prediction markers for the prognosis of patients with CVID.

scholarly journals Genetic Diagnosis Using Whole Exome Sequencing in Common Variable Immunodeficiency

2016 ◽  
Vol 7 ◽  
Author(s):  
Patrick Maffucci ◽  
Charles A. Filion ◽  
Bertrand Boisson ◽  
Yuval Itan ◽  
Lei Shang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Common Variable Immunodeficiency ◽  
Genetic Diagnosis ◽  
Whole Exome ◽  
Common Variable
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