Eberhardt Christiane S, Haas Johannes-Peter, Girschick Hermann, Schwarz Tobias, Morbach Henner, Rösen-Wolff Angela, Foell Dirk, Dannecker Guenther, Schepp Carsten, Ganser Gerd, Honke Nora, Eggermann Thomas, Müller-Berghaus Jan, Wagner Norbert, Ohl Kim, Tenbrock Klaus
Département de l'enfant et de l'adolescent, Hôpitaux Universitaires de Genève, Genève, Switzerland.
Deutsches Zentrum für Kinder- und Jugendrheumatologie, Garmisch-Partenkirchen, Germany.
Pediatr Rheumatol Online J. 2015 Dec 15;13:61. doi: 10.1186/s12969-015-0059-z.
IL-12p40 plays an important role in the activation of the T-cell lines like Th17 and Th1-cells. Theses cells are crucial in the pathogenesis of juvenile idiopathic arthritis. A polymorphism in its promoter region and the genotype IL12p40 pro1.1 leads to a higher production of IL-12p40. We studied whether there is a difference in the distribution of the genotype in patients with JIA and the healthy population.
In 883 patients and 321 healthy controls the IL-12p40 promoter genotype was identified by ARMS-PCR.
There is no association of IL-12p40 pro polymorphism neither in patients with JIA compared to controls nor in subtypes of JIA compared to oligoarthritis. We found a non-significant tendency of a higher prevalence of the genotype pro1.1 in systemic arthritis (32.4%) and in rheumatoid factor negative polyarthritis (30.5%) and a lower pro1.1 genotype in persistent oligoarthritis (20.7%) and in enthesitis-related arthritis (17%). Likelihood of the occurrence of genotype IL12-p40 pro1.1 in patients with systemic arthritis (OR 1.722, CI 95% 1.344-2.615, p 0.0129) and RF-negative polyarthritis (OR 1.576, CI 95% 1.046-2.376, p 0.0367) compared to persistent oligoarthritis was significantly higher. This was also true for comparison of their homozygous genotypes IL-12p40 pro 1.1 and 2.2 in systemic arthritis (OR 1.779, CI 95 % 1.045-3.029, p 0.0338). However, in Bonferroni correction for multiple hypothesis this was not significant.
A tendency of a higher prevalence of the genotype IL-12p40 pro1.1 in systemic arthritis and in rheumatoid factor negative polyarthritis was observed but not significant. Further investigations should be done to clarify the role IL-12p40 in the different subtypes of JIA.
白细胞介素12 p40(IL - 12p40)在激活Th17和Th1等T细胞系中发挥重要作用。这些细胞在幼年特发性关节炎的发病机制中至关重要。其启动子区域的多态性以及基因型IL12p40 pro1.1会导致IL - 12p40产生增加。我们研究了幼年特发性关节炎患者与健康人群中该基因型的分布是否存在差异。
通过扩增阻滞突变系统聚合酶链反应(ARMS - PCR)鉴定883例患者和321例健康对照者的IL - 12p40启动子基因型。
与对照组相比,幼年特发性关节炎患者中IL - 12p40 pro多态性无关联;与少关节炎相比,幼年特发性关节炎各亚型中也无关联。我们发现pro1.1基因型在全身型关节炎(32.4%)和类风湿因子阴性多关节炎(30.5%)中的患病率有升高趋势但不显著,而在持续性少关节炎(20.7%)和附着点炎相关关节炎(17%)中pro1.1基因型患病率较低。与持续性少关节炎相比,全身型关节炎患者(比值比1.722,95%置信区间1.344 - 2.615,p =0.0129)和类风湿因子阴性多关节炎患者(比值比1.576,95%置信区间1.046 - 2.376,p =0.0367)中IL12 - p40 pro1.1基因型出现的可能性显著更高。全身型关节炎中其纯合基因型IL - 12p40 pro 1.1和2.2的比较也是如此(比值比1.779,95%置信区间1.045 - 3.029,p =0.0338)。然而,在多重假设的Bonferroni校正中,这并不显著。
观察到全身型关节炎和类风湿因子阴性多关节炎中IL - 12p40 pro1.1基因型患病率有升高趋势,但不显著。应进一步开展研究以阐明IL - 12p40在幼年特发性关节炎不同亚型中的作用。