Title:Role of Apoptosis in the Pathogenesis of Common Variable Immunodeficiency (CVID)
Volume: 17
Issue: 4
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 and Asghar Aghamohammadi*
Affiliation:
- Children’s Medical Center Hospital, 62 Qarib St., Keshavarz Blvd., Tehran14194,,Iran
- Children’s Medical Center Hospital, 62 Qarib St., Keshavarz Blvd., Tehran14194,,Iran
Keywords:
Common variable immunodeficiency, early apoptosis, late apoptosis, B cell subsets, anti-apoptotic, BCL-2.
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.
