Common variable immunodeficiency (CVID) is a heterogeneous group of diseases characterized by hypogammaglobulinemia, leading to recurrent infections. Defect in maturation of B cells into functional plasma cells is the most principal defect in CVID. B cell maturation antigen (BCMA) is an essential molecule for survival of long-lived plasma cells. The aim of this study is to evaluate BCMA expression on B cells as well as count peripheral blood plasmablast cells in CVID patients compared with healthy individuals. Blood samples were collected from 15 CVID patients and 15 age- and sex-matched normal controls. Genomic RNA was extracted from peripheral blood mononuclear cell samples using an RNX-Plus Kit. cDNA was synthesized from extracted RNA using a RevertAid First Strand cDNA Synthesis Kit. Synthesized cDNA was used as a template for reverse transcription polymerase chain reaction (RT-PCR) to measure BCMA gene expression by Maxima SYBR Green/ROX qPCR Master Mix Kit (Thermo Scientific). Flow cytometry was used to measure plasmablast counts in the peripheral blood. RT-PCR results showed that the expression of BCMA in CVID patients compared with control subjects was significantly decreased and this decrease was statistically significant (P < 0.046). Accordingly, the flow cytometric results demonstrated that the mean percentage of plasmablast cells and BCMA expression in patients was significantly (P < 0.002) decreased in comparison with the control group. Our data show that decreased BCMA expression as well as reduction of plasmablast cell frequency in CVID patients could be involved in development of CVID.
Get full access to this article
View all access options for this article.
References
1.
Cunningham-RundlesC, BodianC. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol, 1999; 92:34–48.
2.
YazdaniR, HeydariA, AziziG, AbolhassaniH, AghamohammadiA. Asthma and allergic diseases in a selected group of patients with common variable immunodeficiency. J Investig Allergol Clin Immunol, 2016; 26:209–211.
3.
AghamohammadiA, FarhoudiA, MoinM, RezaeiN, KouhiA, PourpakZ, et al.Clinical and immunological features of 65 Iranian patients with common variable immunodeficiency. Clin Diagn Lab Immunol, 2005; 12:825–832.
4.
MokhtariM, ShakeriA, MirminachiB, AbolhassaniH, YazdaniR, GrimbacherB, AghamohammadiA. Important factors influencing severity of common variable immunodeficiency. Arch Iran Med, 2016; 19:544–550.
5.
Cunningham-RundlesC. How I treat common variable immune deficiency. Blood, 2010; 116:7–15.
6.
AziziG, AbolhassaniH, Hosein AsgardoonM, RahnavardJ, YazdaniR, MohammadiJ, et al.The use of immunoglobulin therapy in primary immunodeficiency diseases. Endocr Metab Immune Disord Drug Targets, 2016; 16:80–88.
7.
RezaeiN, AghamohammadiA, KardarG, NourizadehM, PourpakZ. T-helper 1 and 2 cytokine assay in patients with common variable immunodeficiency. J Investig Allergol Clin Immunol, 2008; 18:449–453.
8.
Ganjalikhani-HakemiM, YazdaniR, SherkatR, HomayouniV, MasjediM, HosseiniM. Evaluation of the T helper 17 cell specific genes and the innate lymphoid cells counts in the peripheral blood of patients with the common variable immunodeficiency. J Res Med Sci, 2014; 19(Suppl. 1):S30–S35.
9.
YazdaniR, FatholahiM, Ganjalikhani-HakemiM, AbolhassaniH, AziziG, HamidKM, et al.Role of apoptosis in common variable immunodeficiency and selective immunoglobulin A deficiency. Mol Immunol, 2016; 71:1–9.
10.
AziziG, RezaeiN, KiaeeF, TavakoliniaN, YazdaniR, MirshafieyA, et al.T cell abnormalities in common variable immunodeficiency. J Investig Allergol Clin Immunol, 2016; 26:233–243.
11.
YazdaniR, HakemiMG, SherkatR, MasjediM, ZarkeshH, HosseiniM. Evaluation of IL-17 gene expression in the peripheral blood of patients with common variable immunodeficiency. J Isfahan Med Sch, 2013; 31:358–363.
12.
YazdaniR, AbolhassaniH, RezaeiN, AziziG, HammarströmL, AghamohammadiA. Evaluation of known defective signaling-associated molecules in patients who primarily diagnosed as common variable immunodeficiency. Int Rev Immunol, 2016; 35:7–24.
13.
Martinez-GalloM, RadiganL, AlmejunMB, Martinez-PomarN, MatamorosN, Cunningham-RundlesC. TACI mutations and impaired B-cell function in subjects with CVID and healthy heterozygotes. J Allergy Clin Immunol, 2013; 131:468–476.
14.
AgarwalS, SmerekaP, HarpazN, Cunningham-RundlesC, MayerL. Characterization of immunologic defects in patients with common variable immunodeficiency (CVID) with intestinal disease. Inflamm Bowel Dis, 2011; 17:251–259.
15.
AhnS, Cunningham-RundlesC. Role of B cells in common variable immune deficiency. Expert Rev Clin Immunol, 2009; 5:557–564.
16.
TaubenheimN, von HornungM, DurandyA, WarnatzK, CorcoranL, PeterHH, et al.Defined blocks in terminal plasma cell differentiation of common variable immunodeficiency patients. J Immunol, 2005; 175:5498–5503.
17.
CastigliE, GehaRS. Molecular basis of common variable immunodeficiency. J Allergy Clin Immunol, 2006; 117:740–746.
18.
BensonMJ, DillonSR, CastigliE, GehaRS, XuS, LamKP, et al.Cutting edge: the dependence of plasma cells and independence of memory B cells on BAFF and APRIL. J Immunol, 2008; 180:3655–3659.
19.
YangM, HaseH, Legarda-AddisonD, VarugheseL, SeedB, TingAT. B cell maturation antigen, the receptor for a proliferation-inducing ligand and B cell-activating factor of the TNF family, induces antigen presentation in B cells. J Immunol, 2005; 175:2814–2824.
20.
BurmesterGR, FeistE, DornerT. Emerging cell and cytokine targets in rheumatoid arthritis. Nat Rev Rheumatol, 2014; 10:77–88.
21.
O'ConnorBP, RamanVS, EricksonLD, CookWJ, WeaverLK, AhonenC, et al.BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med, 2004; 199:91–98.
22.
CoqueryCM, EricksonLD. Regulatory roles of the tumor necrosis factor receptor BCMA. Crit Rev Immunol, 2012; 32:287–305.
RyanMC, HeringM, PeckhamD, McDonaghCF, BrownL, KimKM, et al.Antibody targeting of B-cell maturation antigen on malignant plasma cells. Mol Cancer Ther, 2007; 6:3009–3018.
25.
OdenF, MarinoSF, BrandJ, ScheuS, KriegelC, OlalD, et al.Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma. Mol Oncol, 2015, 9:1348–1358.
26.
ChapelH, LucasM, LeeM, BjorkanderJ, WebsterD, GrimbacherB, et al.Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood, 2008; 112:277–286.
27.
Bukowska-StrakovaK, KowalczykD, BaranJ, SiedlarM, KobylarzK, ZembalaM. The B-cell compartment in the peripheral blood of children with different types of primary humoral immunodeficiency. Pediatr Res, 2009; 66:28–34.
28.
SchwartzR, PoratYB, HandzelZ, SthoegerZ, GartyBZ, Confino-CohenR, et al.Identification of a subset of common variable immunodeficiency patients with impaired B-cell protein tyrosine phosphorylation. Clin Diagn Lab Immunol, 1999; 6:856–860.
29.
WarnatzK, DenzA, DragerR, BraunM, GrothC, Wolff-VorbeckG, et al.Severe deficiency of switched memory B cells (CD27(+)IgM(−)IgD(−)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood, 2002; 99:1544–1551.
30.
UngerS, SeidlM, Schmitt-GraeffA, BohmJ, SchrenkK, WehrC, et al.Ill-defined germinal centers and severely reduced plasma cells are histological hallmarks of lymphadenopathy in patients with common variable immunodeficiency. J Clin Immunol, 2014; 34:615–626.
31.
YazdaniR, SeifyR, Ganjalikhani-HakemiM, AbolhassaniH, EskandariN, Golsaz-ShiraziF, et al.Comparison of various classifications for patients with common variable immunodeficiency (CVID) using measurement of B-cell subsets. Allergol Immunopathol, 2016. DOI: 10.1016/j.aller.2016.07.001. [epub ahead of print]
32.
SalzerU, NeumannC, ThielJ, WoellnerC, Pan-HammarstromQ, LougarisV, et al.Screening of functional and positional candidate genes in families with common variable immunodeficiency. BMC Immunol, 2008; 9:3.
33.
LuoJ, NiuX, ZhangM, ZhangK, ChenM, DengS. Inhibition of B lymphocyte-induced maturation protein-1 reduces the production of autoantibody and alleviates symptoms of systemic lupus erythematosus. Autoimmunity, 2015; 48:80–86.
34.
JacobCO, YuN, GuoS, JacobN, QuinnWJ, 3rd, SindhavaV, et al.Development of systemic lupus erythematosus in NZM 2328 mice in the absence of any single BAFF receptor. Arthritis Rheum, 2013; 65:1043–1054.
35.
BellucciR, AlyeaEP, ChiarettiS, WuCJ, ZornE, WellerE, et al.Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor. Blood, 2005; 105:3945–3950.
36.
AnsariM, Ganjalikhani-HakemiM, SherkatR, RezaeiA, YazdaniR, KhosraviS. Evaluation of mutation in B cell maturation antigen (BCMA) gene in patients with common variable immunodeficiency (CVID). J Isfahan Med Sch, 2016; 34:555–562.
37.
Jin RKH, SuzukiH, AraiT, TeramotoT, FukaoT, et al.Age-related changes in BAFF and APRIL profiles and upregulation of BAFF and APRIL expression in patients with primary antibody deficiency. Int J Mol Med, 2008; 21:233–238.
38.
Sarantopoulos ATK, SkendrosP, BougiouklisD, TheodorouI, BouraP. Genetic polymorphism study of regulatory B cell molecules and cellular immunity function in an adult patient with common variable immunodeficiency. Hippokratia, 2008; 12:188–190.
39.
YazdaniR, Ganjalikhani-HakemiM, EsmaeiliM, AbolhassaniH, VaeliS, RezaeiA, et al.Impaired Akt phosphorylation in B-cells of patients with common variable immunodeficiency. Clin Immunol, 2016. DOI: 10.1016/j.clim.2016.09.009.
40.
ShenX, GuoY, QiJ, ShiW, WuX, JuS. Binding of B‐cell maturation antigen to B‐cell activating factor induces survival of multiple myeloma cells by activating Akt and JNK signaling pathways. Cell Biochem Funct, 2016; 34:104–110.
