Impaired Akt Phosphorylation in B-Cells of Patients With Common Variable Immunodeficiency Publisher Pubmed

Summary: Research shows defective cell signaling in CVID patients’ B-cells, linked to higher cell death and poor vaccine response, hinting at new treatment targets. #Immunodeficiency #BCells

Yazdani R^{1, 2, 3} ; Ganjalikhanihakemi M¹ ; Esmaeili M⁴ ; Abolhassani H^{2, 5} ; Vaeli S⁴ ; Rezaei A¹ ; Sharifi Z⁴ ; Azizi G⁶ ; Rezaei N^{2, 7, 8} ; Aghamohammadi A^{2, 9}
Source: Clinical Immunology Published:2017

Abstract

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. © 2016 Elsevier Inc.