Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6116977 | Immunology Letters | 2016 | 33 Pages |
Abstract
Common variable immunodeficiency (CVID) is a heterogeneous disease characterized by impaired B-cell differentiation and maturation accompanied with the defective antibody production. Several investigators addressed the possibility that disturbed cytokine production of TNF, IL-6, IFN-γ and IL-10, among a variety of others, may be implicated in CVID. The aim of this study was to test the hypothesis that genetic polymorphisms involving TNF (â308G/A), IFNG (+874 T/A), IL10 (â1082G/A, â819T/C and â592A/C), and IL6 (â174G/C) cytokine genes might contribute to susceptibility to CVID. Thirty five patients with CVID and 250 healthy controls were genotyped for indicated single nucleotide polymorphisms (SNP) in TNF, IL6, IFNG and IL10 using Taqman-based assays. CVID patients had significantly higher frequency of TNF A allele and AA genotype than in healthy subjects (p = 0.006; OR = 2.27; 95%CI = 1.24-4.17 and p = 0.038, OR = 15.64; 95%CI = 1.38-177.20, respectively). In addition, the frequency of GG genotype was significantly higher in healthy controls than in patient group (p = 0.019, OR = 0.43, 95%CI = 0.21-0.89). Genetic analysis of IL6 SNP showed that allele G confers increased risk for CVID (p = 0.037, OR = 1.78, 95% CI = 1.03-3.08) while IFNG allele T was associated with splenomegaly in CVID (p = 0.032; OR = 2.86; 95% CI = 1.08-7.56). We observed no association between genotypes, alleles and haplotypes of IL-10 gene and CVID or its clinical complications. In conclusion, our results indicated association between CVID and cytokine gene polymorphisms â308 G/A TNF and â174G/C IL6. In addition, we demonstrated that splenomegaly, one of the most common complications in this disease, is associated with +874T/A IFNG polymorphism. These findings add further support to the notion that cytokines may play significant role in pathogenesis of this primary antibody deficiency. However, further investigation that would involve a larger study group of CVID patients is warranted to confirm our findings.
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Authors
Dijana Perovic, Vladimir Perovic, Vera Pravica, Branka Bonaci-Nikolic, Radovan Mijanovic, Vera Bunjevacki,