Tanhapour M, Vaisi-Raygani A, Bahrehmand F, Khazaei M, Kiani A, Rahimi Z, Nomani H, Tavilani H, Pourmotabbed T
Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Tissue Engineering and Regenerative Medicine (TERM) Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Cell Mol Biol (Noisy-le-grand). 2016 Oct 31;62(12):56-61. doi: 10.14715/cmb/2016.62.12.10.
The cytotoxic T lymphocyte antigen-4 (CTLA-4) also known as CD152 (cluster of differentiation 152) is a crucial negative regulator of the immune system. This protein receptor provides negative signals in order to suppress T-cell activation and immune attack against self-antigens, although its role is unclear. The ability of CTLA-4 to limit T cell-mediated immune response has made it a major target in treatment of tumors and autoimmune diseases such as systemic lupus erythematosus (SLE). In this study, we investigated whether CTLA-4 G-1661A and CTLA-4 T-1722C mutations are associated with SLE. So one hundred nine SLE patients and 101 gender and age-matched unrelated healthy controls were recruited for this case-control study. The promoter mutations were detected by PCR-RFLP, neopterin, malondialdehyde (MDA) and serum lipid concentration were determined by HPLC and enzyme assay, respectively.
We found that both codominant (AA vs. GG) and recessive (AA vs. GA+GG) CTLA-4 G-1661A mutation significantly decreased the risk of SLE by 1.7 and 3.7 times, respectively. Interestingly, SLE patients with AA genotypes of CTLA-4 G-1661A have lower neopterin and MDA concentration compared with GA+GG genotypes. The overall distribution of CTLA-4 T-1722C genotypes and alleles in SLE patients were similar to those in control group. In conclusion, our findings showed, that there is an association between systemic inflammatory markers, oxidative stress and the CTLA-4 G-1661A GG+AG genotypes, MDA and neopterin which are the most conventional risk factors for coronary heart disease, therefore these mutations may be consider as a risk factor for susceptibility to heart disease in SLE patients.
细胞毒性T淋巴细胞抗原4（CTLA-4）也称为CD152（分化簇152），是免疫系统的关键负调节因子。这种蛋白质受体提供负信号以抑制T细胞活化和针对自身抗原的免疫攻击，尽管其作用尚不清楚。CTLA-4限制T细胞介导的免疫反应的能力使其成为治疗肿瘤和自身免疫性疾病（如系统性红斑狼疮（SLE））的主要靶点。在本研究中，我们调查了CTLA-4 G-1661A和CTLA-4 T-1722C突变是否与SLE相关。因此，招募了109例SLE患者和101例性别和年龄匹配的无关健康对照进行这项病例对照研究。通过PCR-RFLP检测启动子突变，分别通过HPLC和酶法测定新蝶呤、丙二醛（MDA）和血清脂质浓度。
我们发现，共显性（AA与GG）和隐性（AA与GA+GG）CTLA-4 G-1661A突变分别使SLE风险显著降低1.7倍和3.7倍。有趣的是，与GA+GG基因型相比，CTLA-4 G-1661A的AA基因型SLE患者的新蝶呤和MDA浓度较低。SLE患者中CTLA-4 T-1722C基因型和等位基因的总体分布与对照组相似。总之，我们的研究结果表明，全身炎症标志物、氧化应激与CTLA-4 G-1661A GG+AG基因型、MDA和新蝶呤之间存在关联，而MDA和新蝶呤是冠心病最常见的危险因素，因此这些突变可能被视为SLE患者患心脏病易感性的危险因素。
