El Gazzar Iman I, Fathy Hanan M, Gheita Tamer A, Nour El-Din Abeer M, Rasheed Enas Abdel, Bassyouni Rasha H, Kenawy Sanaa A
Rheumatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Rheumatology Department, Faculty of Medicine, Fayoum University, Faiyum, Egypt.
Clin Rheumatol. 2017 Aug;36(8):1757-1763. doi: 10.1007/s10067-017-3719-1. Epub 2017 Jun 7.
The study aims to evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and -308 A/G promoter polymorphism in juvenile idiopathic arthritis (JIA) patients and find any association to the subsets, clinical and laboratory features, disease activity, and damage as well as functional disability. Forty-eight JIA children and 30 controls were included in the present study. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated, juvenile arthritis damage index (JADI) was assessed, and Childhood Health Assessment Questionnaire (CHAQ) measured the functional status. Serum TNF-α was assayed by ELISA and gene (-308) promoter polymorphism was determined by polymerase chain reaction. The 48 JIA children (mean age 11.5 ± 2.8 years) were 13 systemic, 17 oligoarticular, and 18 polyarticular onset. The serum TNF-α was significantly higher in patients (90.4 ± 6.3 ng/ml) compared to control (3.5 ± 2.6 ng/ml) (p < 0.0001) with a tendency to be higher in the polyarticular subtype. All controls had TNF-α -308 GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-α significantly correlated with JADAS-27 (r = 0.32, p = 0.03) and CHAQ (r = 0.37, p = 0.01) and negatively with the presence of GG alleles (r = -0.48, p = 0.001). The GG alleles were significantly negatively associated with C-reactive protein (r = -0.32, p = 0.03) with a tendency to negatively correlate with JADAS-27, CHAQ, and JADI-extrarticular (r = -0.28, p = 0.06; r = -0.25, p = 0.09 and r = -0.25, p = 0.09, respectively). There is evidence of a possible influence of the -308 SNP promoter position on the production of TNF-α, the severity of JIA which may consequently influence the response to anti-TNF-α treatment.
本研究旨在评估青少年特发性关节炎（JIA）患者血清肿瘤坏死因子α（TNF-α）水平及-308 A/G启动子多态性的临床意义，并找出其与疾病亚型、临床和实验室特征、疾病活动度、损伤以及功能残疾之间的关联。本研究纳入了48例JIA患儿和30例对照。计算27个关节的青少年关节炎疾病活动评分（JADAS-27），评估青少年关节炎损伤指数（JADI），并通过儿童健康评估问卷（CHAQ）测量功能状态。采用酶联免疫吸附测定法（ELISA）检测血清TNF-α，通过聚合酶链反应测定基因（-308）启动子多态性。48例JIA患儿（平均年龄11.5±2.8岁）中，13例为全身型，17例为少关节型，18例为多关节型起病。与对照组（3.5±2.6 ng/ml）相比，患者血清TNF-α显著升高（90.4±6.3 ng/ml）（p<0.0001），多关节型亚型中TNF-α有升高趋势。所有对照均为TNF-α -308 GG等位基因。与少关节型和多关节型亚型相比，全身型起病中GG基因型频率有升高趋势。血清TNF-α与JADAS-27显著相关（r=0.32，p=0.03），与CHAQ相关（r=0.37，p=0.01），与GG等位基因存在呈负相关（r=-0.48，p=0.001）。GG等位基因与C反应蛋白显著负相关（r=-0.32，p=0.03），与JADAS-27、CHAQ和关节外JADI有负相关趋势（r=-0.28，p=0.06；r=-0.25，p=0.09；r=-0.25，p=0.09）。有证据表明-308 SNP启动子位置可能对TNF-α的产生、JIA的严重程度有影响，进而可能影响抗TNF-α治疗的反应。
