Role of Apoptosis in the Pathogenesis of Common Variable Immunodeficiency (CVID)

Author(s): Mazdak Ganjalikhani-Hakemi, Reza Yazdani*, Mohammad Esmaeili, Hassan Abolhassani, Wiliam Rae, Gholamreza Azizi, Majid Z. dizaji, Mohammadreza Shaghaghi, Abbas Rezaei, Faezeh Abbasi-Rad, Sanaz Afshar-Qasemloo, Saeed Mohammadi, Nima Rezaei, Asghar Aghamohammadi*.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 17 , Issue 4 , 2017

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Graphical Abstract:


Background: Common variable immunodeficiency (CVID) is a heterogeneous immune deficiency characterized by hypogammaglobulinemia. Since B cell maturation and differentiation is defective in this disorder, we evaluated apoptosis in B cells of patients with CVID compared with healthy donors (HD).

Methods: Determination of peripheral blood B-cell subsets in CVID and HDs, was performed using flow cytometry. We compared total apoptosis, early apoptosis and late apoptosis/necrosis in unstimulated and stimulated B-cells of patients with CVID and HDs. We also assessed the expression of the anti-apoptotic molecule BCL2 mRNA levels in B-cells by real-time PCR in CVID patients compared with HDs.

Results: Total B-cell apoptosis was increased in both unstimulated and stimulated B-cells from CVID patients compared with HDs (p=0.02 and p=0.004). Early apoptosis in stimulated B-cells (p=0.04) and late apoptosis/necrosis of B-cells in both unstimulated and stimulated B-cells (p=0.04 and p=0.03, respectively) were significantly higher in CVID patients compared with HDs. There was a significant inverse correlation between the percentages of post germinal center B-cells in the peripheral blood of CVID patients compared with percentage of apoptotic B-cells. However, anti-apoptotic BCL2 expression was not significantly reduced in B-cells from CVID patients compared with HDs (p=0.16).

Conclusion: Increased apoptosis of B-cells may be a factor in abnormality of differentiated B-cell subsets and the impaired endogenous immunoglobulin production in CVID patients. Further studies of the expression of pro/anti-apoptotic mediators in B-cells of CVID patients may shed light on the mechanism behind this increased B-cell apoptosis, and present potential therapeutic interventions in the future.

Keywords: Common variable immunodeficiency, early apoptosis, late apoptosis, B cell subsets, anti-apoptotic, BCL-2.

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Article Details

Year: 2017
Page: [332 - 340]
Pages: 9
DOI: 10.2174/1871530317666170919120245
Price: $65

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