Paradowska-Gorycka Agnieszka, Jurkowska Monika, Czuszynska Zenobia, Felis-Giemza Anna, Mańczak Malgorzata, Zdrojewski Zbigniew, Olesinska Marzena
Department of Biochemistry and Molecular Biology, Institute of Rheumatology , Warsaw , Poland.
Mod Rheumatol. 2015 May;25(3):487-9. doi: 10.3109/14397595.2014.951143. Epub 2014 Aug 27.
Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disease with a prevalence of about 10 cases/100,000. It seems that in the pathogenesis of MCTD no individual cytokines/cells, but rather an altered pattern of these markers altogether may contribute to the autoimmune processes and their balance determines disease activity. IL-10, IL-12 and IL-17F as inflammatory cytokines might be an important functional candidate genes for autoimmune diseases including MCTD.
The study group consisted of 66 patients with MCTD and of 106 (163 for IL-12B) healthy individuals. SNPs in the IL-10 (- 592C/A, - 1082G/A), IL-12B (+ 1188A/C) and IL-17F (His161Arg, Glu126Gly) genes were investigated by PCR-RFLP approach.
The frequency of the IL-10-592A and -1082A allele was higher in MCTD patients than in control groups (both p = 0,0000). In addition the -1082G/A IL-10 gene polymorphism was associated with esophageal involvement and with anti-U1-A and -C antibodies. The IL-17 7488A/G variant showed correlation with presence of anti-SmB and anti-dsDNA antibodies, while the IL-17F 7383A/G variant was associated with Sjögren's syndrome and leuco-and thrombocytopenia. Moreover, the IL-12 SNP + 1188A/C showed correlation with sclerodactyly in MCTD patients.
Present findings indicate that IL-10 gene variants may be considered as genetic risk factors for MCTD susceptibility.
混合性结缔组织病（MCTD）是一种罕见的系统性自身免疫性疾病，患病率约为10/10万。在MCTD的发病机制中，似乎不是单个细胞因子/细胞，而是这些标志物的改变模式共同促成了自身免疫过程，并且它们之间的平衡决定了疾病活动。白细胞介素-10（IL-10）、白细胞介素-12（IL-12）和白细胞介素-17F（IL-17F）作为炎性细胞因子，可能是包括MCTD在内的自身免疫性疾病的重要功能候选基因。
研究组由66例MCTD患者和106名（IL-12B基因检测为163名）健康个体组成。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法研究IL-10基因（-592C/A、-1082G/A）、IL-12B基因（+1188A/C）和IL-17F基因（His161Arg、Glu126Gly）中的单核苷酸多态性（SNP）。
MCTD患者中IL-10 -592A和-1082A等位基因的频率高于对照组（p值均为0.0000）。此外，IL-10基因-1082G/A多态性与食管受累以及抗U1-A和抗U1-C抗体相关。IL-17 7488A/G变异与抗SmB和抗双链DNA（dsDNA）抗体的存在相关，而IL-17F 7383A/G变异与干燥综合征以及白细胞减少和血小板减少相关。此外，IL-12基因SNP +1188A/C与MCTD患者的指（趾）硬皮病相关。
目前的研究结果表明，IL-10基因变异可能被视为MCTD易感性的遗传危险因素。
