F.85. Differences After Heterologous T Cell Dependent Costimulation in B Cells from Common Variable Immunodeficiency (CVID) Patients and Healthy Controls

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.

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Immunophenotyping of putative human B1 B cells in healthy controls and common variable immunodeficiency (CVID) patients

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.2012.04656.x ◽

2012 ◽

Vol 170 (3) ◽

pp. 333-341 ◽

Cited By ~ 18

Author(s):

O. Suchanek ◽

R. Sadler ◽

E. A. Bateman ◽

S. Y. Patel ◽

B. L. Ferry

Keyword(s):

B Cells ◽

Common Variable Immunodeficiency ◽

Healthy Controls ◽

Common Variable ◽

B1 B Cells

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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 ◽

10.18502/ijaai.v20i6.8021 ◽

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.

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Functional abnormalities of CD8+ T cells define a unique subset of patients with common variable immunodeficiency

Blood ◽

10.1182/blood.v82.1.192.bloodjournal821192 ◽

1993 ◽

Vol 82 (1) ◽

pp. 192-201 ◽

Cited By ~ 43

Author(s):

JS Jaffe ◽

W Strober ◽

MC Sneller

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Cd8 T Cells ◽

Common Variable Immunodeficiency ◽

Cytokine Production ◽

Interleukin 2 ◽

T Cell Subsets ◽

Cell Phenotype ◽

Common Variable

A substantial subgroup of patients with common variable immunodeficiency (CVI) exhibit an abnormal T-cell phenotype characterized by a low CD4/CD8 ratio associated with a significant increase in the absolute number of CD8+ T cells (CVI4/8low patients). In the present study, we examined the phenotypic and functional properties of purified T-cell subsets in this group of CVI patients. CD8+ T cells from CVI4/8low patients manifested increased expression of HLA-DR and CD57 and decreased expression of CD45RA as compared with CD8+ T cells from normal controls. When stimulated with anti-CD3 and phorbol 12-myristate 13-acetate, purified patient CD8+ T cells exhibited significantly decreased proliferation, c-myc expression, and interleukin-2 (IL-2) production compared with that of normal CD8+ T cells. Nevertheless, mitogen-activated patient CD8+ T cells secreted elevated amounts of gamma-interferon and IL-5 and normal amounts of IL- 4. This abnormal pattern of proliferation and cytokine production was limited to the CD8+ T-cell subset as CD4+ T cells from these patients exhibited normal proliferation and cytokine production. In further functional studies, purified CD8+ T cells from CVI4/8low patients manifested increased cytotoxic T-lymphocyte activity and suppressor activity, as compared with normal CD8+ T cells, when they were tested in (1) an anti-CD3 “redirected” cytotoxicity assay and (2) a suppressor assay consisting of CD8+ T cells and Staphylococcus aureus Cowan I (SAC) plus IL-2-stimulated normal (allogeneic) B cells. In the latter case, patient CD8+ T cells suppressed IgG production, but not IgM production. Finally, in studies to evaluate the role of patient CD8+ T cells in the pathogenesis of hypogammaglobulinemia, we determined the capacity of SAC and IL-2 to induce Ig production in highly purified patient B cells, ie, in the absence of patient CD8+ T cells. We found that, whereas B cells from one patient produced normal amounts of IgG, B cells from three patients were unable to produce normal amounts of IgG under these conditions. These data establish the phenotypic and functional characteristics of CD8+ T cells in CVI4/8low and clearly distinguish CVI4/8low patients from other patients with this syndrome. The data do not support the contention that hypogammaglobulinemia in CVI4/8low patients is due to a direct effect of CD8+ T cells on terminal B-cell differentiation, except in the occasional patient. The abnormal CD8+ T cells may, nevertheless, have more subtle effects of lymphoid function that play a role in disease pathogenesis.

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COMMON VARIABLE IMMUNODEFICIENCY, DEPENDENT COSTIMULATION B CELLS MOLECULES AND AUTOIMMUNE HEMATOLOGICAL DISEASES IN ADULTS.

10.26226/morressier.57bc1755d462b80290b4d8b2 ◽

2016 ◽

Author(s):

Patricia O Farrill

Keyword(s):

B Cells ◽

Common Variable Immunodeficiency ◽

Hematological Diseases ◽

Common Variable

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Faculty Opinions recommendation of Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1166205.627133 ◽

2009 ◽

Author(s):

Francisco A Bonilla

Keyword(s):

B Cells ◽

Common Variable Immunodeficiency ◽

Common Variable

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Oxidative stress in common variable immunodeficiency

European Journal of Inflammation ◽

10.1177/20587392211002411 ◽

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.

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