Impaired Akt phosphorylation in B-cells of patients with common variable immunodeficiency.
Common variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency characterized by recurrent infections. We evaluated whether defective PI3K/Akt/FoxO pathway could influence B-cell fate. Determination of B-cell subsets in CVD patients and healthy donors (HDs) were performed using flow cytometry. We evaluated mRNA and protein expression of PI3K, Akt and FoxO using real-time PCR and flow cytometry, respectively. Moreover, phosphorylated Akt (pAkt) expression in B-cells has been measured by flowcytometry. We identified a significant reduction in the percentage of marginal zone like B-cells, memory B-cells (total, switched and unswitched) and plasmablasts in patients, as these decreased B-cell subsets had a significant negative correlation with increased apoptosis in patients. Surprisingly, we identified decreased pAkt expression in B-cells of patients than HDs. We described for the first time impaired pAkt expression in B-cells of CVID patients that had a significant correlation with antibody response to the vaccine and worse clinical complications.
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran; Molecular Immunology Interest Group (MIIG), Universal Scientific Education and Research Network (USERN), Isfahan, Iran.
Reza
R
Yazdani
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: mghakemi@med.mui.ac.ir.
Mazdak
M
Ganjalikhani-Hakemi
Department of Virology, Iranian Blood Transfusion Organization, Tehran, Iran.
Mohammad
M
Esmaeili
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran; Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Stockholm, Sweden.
Hassan
H
Abolhassani
Department of Virology, Iranian Blood Transfusion Organization, Tehran, Iran.
Shahram
S
Vaeli
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Abbas
A
Rezaei
Department of Virology, Iranian Blood Transfusion Organization, Tehran, Iran.
Zohre
Z
Sharifi
Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences, Karaj, Iran.
Gholamreza
G
Azizi
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Science, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Boston, MA, USA.
Nima
N
Rezaei
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran; Primary Immunodeficiency Disease Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran. Electronic address: aghamohammadi@sina.tums.ac.ir.
Asghar
A
Aghamohammadi
D000293:Adolescent; D000328:Adult; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002648:Child; D017074:Common Variable Immunodeficiency / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D055815:Young Adult
D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
Antibody response; B-cell; Common variable immunodeficiency; PI3K/Akt/FoxO pathway; Phosphorylated Akt