期刊
JOURNAL OF HEMATOLOGY & ONCOLOGY
卷 9, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13045-016-0261-6
关键词
CD3 zeta; CD28; CTLA-4; Cbl-b; CD3 zeta; 3 '-UTR splice variant; SNP; Gene expression level; AA
资金
- National Natural Science Foundation of China [81370605, 81460026]
- China Post-doctoral Science Foundation funded project [20070410840]
- Natural Science Foundation of Guangdong Province [S2012010008794, S2013020012863]
- Technology Program of Guangdong Province [2014A020212209]
- Foundation for High-level Talents in Higher Education of Guangdong, China [[2013]246-54]
- Fundamental Research Funds for the Central Universities [21612425]
- Science and Information Technology of Guangzhou
Background: A previous study has demonstrated a significantly increased CD3 zeta gene expression level in aplastic anemia (AA). However, the mechanism underlying the upregulated CD3 zeta mRNA expression level and that of T cell activation signaling molecules in AA patients remains unclear. Thus, we investigated the expression levels of the CD3 zeta, CD28, CTLA-4, and Cbl-b genes, the SNP rs231775 in the CTLA-4 gene, and the distribution of the CD3 zeta 3'-UTR splice variant in AA patients. Methods: CD3 zeta 3'-UTR splice variants were identified in peripheral blood mononuclear cells (PBMCs) from 48 healthy individuals and 67 patients with AA [37 cases of severe aplastic anemia (SAA) and 30 cases of non-sever aplastic anemia (NSAA)] by RT-PCR. CD3 zeta, CD28, CTLA-4, and Cbl-b gene expression was analyzed by real-time quantitative PCR. The SNP rs231775 in CTLA-4 gene was analyzed by PCR-RFLP. Results: CD3 zeta and CD28 expression was significantly higher, while CTLA-4 and Cbl-b expression was significantly lower in AA patients compared with healthy individuals. Significantly higher CD3 zeta expression was found in the NSAA subgroup compared with the SAA subgroup. 64 % of the AA samples had the same genotype (WT+ AS(+) CD3 zeta 3'-UTR); 22 % of the AA patients had a WT(+)AS(-)CD3 zeta 3'-UTR genotype, and 14 % of the AA patients had a WT- AS (+)CD3 zeta 3'-UTR genotype. The CD3 zeta expression level of WT(-)AS(+) subgroup was the highest in the SAA patients. A significantly higher frequency of the GG genotype (mutant type, homozygous) of SNP rs231775 in CTLA-4 gene was found in the AA patients. Positive correlation between the CTLA-4 and Cbl-b gene expression levels was found in healthy individuals with the AA and AG genotypes, but not in the AA patients. Conclusions: This is the first study analyzing the expression characteristics of the CD28, CTLA-4, and Cbl-b genes in AA. Our results suggest that aberrant T cell activation may be related to the first and second signals of T cell activation in AA. The GG genotype of SNP rs231775 in CTLA-4 gene might be associated with AA risk in the Chinese population. The characteristics of CD3 zeta 3'-UTR alternative splicing may be an index for evaluating the T cell activation status in AA patients, particularly in SAA patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据