Cimaz Rolando, Cazalis Marie-Angélique, Reynaud Charlotte, Gerloni Valeria, Zulian Francesco, Biggioggero Martina, Martini Giorgia, Pontikaki Irene, Fantini Flavio, Mougin Bruno, Miossec Pierre
Unité Mixte Hospices Civils de Lyon-BioMérieux, Lyon, France.
Ann Rheum Dis. 2007 Jul;66(7):900-4. doi: 10.1136/ard.2006.067454. Epub 2007 Feb 26.
To investigate the genetic contribution of cytokine gene polymorphisms (interleukin 1 (IL1) and tumour necrosis factor alpha (TNFalpha)) on disease phenotype and on response to TNF-blocking agents in a population of patients with juvenile idiopathic arthritis (JIA).
A cohort of 107 consecutive patients with JIA who were receiving treatment with anti-TNF agents was enrolled in this study. Analysis of genetic polymorphisms for IL1B +3954, IL1RA +2018, TNFalpha -238 and TNFalpha -308 was performed by enzyme-linked oligo sorbent assay, and compared with those obtained from 630 healthy Caucasians and 263 adult patients with rheumatoid arthritis. Relevant demographic, clinical and laboratory data were collected from clinical charts and entered into a customised database, and chi(2) analysis was performed to compare cytokine polymorphisms with disease type according to the International League of Associations for Rheumatology criteria, presence of uveitis, rheumatoid factor and anti-nuclear antibody positivity, erosive disease, frequency of adverse effects to anti-TNF and clinical response after 3 months.
The T/T genotype of the IL1B +3954 polymorphism was absent in patients with JIA and present in 5% of controls (p = 0.015). No significant correlation was found between the studied polymorphisms and clinical or laboratory variables considered. Clinical response to TNF inhibitors at 3 months was not associated with the genetic polymorphisms considered.
In our cohort, the absence of the rare IL1B +3954 gene polymorphism was associated with JIA, but without specificity to particular disease phenotypes. The TNF and IL1 gene polymorphism studied did not seem to be associated with response to anti-TNF treatment.
在一组幼年特发性关节炎（JIA）患者中，研究细胞因子基因多态性（白细胞介素1（IL1）和肿瘤坏死因子α（TNFα））对疾病表型以及对TNF阻断剂反应的遗传贡献。
本研究纳入了107例连续接受抗TNF药物治疗的JIA患者队列。通过酶联寡核苷酸吸附测定法对IL1B +3954、IL1RA +2018、TNFα -238和TNFα -308的基因多态性进行分析，并与630名健康白种人和263名成年类风湿关节炎患者的结果进行比较。从临床病历中收集相关的人口统计学、临床和实验室数据，并输入定制数据库，采用卡方分析根据国际风湿病联盟标准比较细胞因子多态性与疾病类型、葡萄膜炎的存在、类风湿因子和抗核抗体阳性、侵蚀性疾病、抗TNF不良反应的频率以及3个月后的临床反应。
JIA患者中不存在IL1B +3954多态性的T/T基因型，而在5%的对照组中存在（p = 0.015）。在所研究的多态性与所考虑的临床或实验室变量之间未发现显著相关性。3个月时对TNF抑制剂的临床反应与所考虑的基因多态性无关。
在我们的队列中，罕见的IL1B +3954基因多态性的缺失与JIA相关，但对特定疾病表型无特异性。所研究的TNF和IL1基因多态性似乎与抗TNF治疗的反应无关。
