Yazdani Reza, Ganjalikhani-Hakemi Mazdak, Esmaeili Mohammad, Abolhassani Hassan, Vaeli Shahram, Rezaei Abbas, Sharifi Zohre, Azizi Gholamreza, Rezaei Nima, Aghamohammadi Asghar
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.
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Clin Immunol. 2017 Feb;175:124-132. doi: 10.1016/j.clim.2016.09.009. Epub 2016 Sep 21.
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.
常见变异型免疫缺陷（CVID）是一组以反复感染为特征的原发性免疫缺陷疾病。我们评估了PI3K/Akt/FoxO信号通路缺陷是否会影响B细胞命运。采用流式细胞术检测CVID患者和健康供体（HDs）的B细胞亚群。我们分别使用实时PCR和流式细胞术评估PI3K、Akt和FoxO的mRNA和蛋白表达。此外，通过流式细胞术检测B细胞中磷酸化Akt（pAkt）的表达。我们发现患者边缘区样B细胞、记忆B细胞（总记忆B细胞、类别转换记忆B细胞和未类别转换记忆B细胞）和成浆细胞的百分比显著降低，因为这些减少的B细胞亚群与患者凋亡增加呈显著负相关。令人惊讶的是，我们发现患者B细胞中的pAkt表达低于HDs。我们首次描述了CVID患者B细胞中pAkt表达受损，这与疫苗抗体反应和更严重的临床并发症显著相关。
