Identification of cellular and serum biomarkers indicating response to methotrexate (MTX) treatment in patients with juvenile uveitis

幼年特发性关节炎(JIA)是儿童最常见的风湿病。眼部受累表现为前葡萄膜炎是常见的，特别是在少关节亚型关节炎的儿童。甲氨蝶呤(MTX)是治疗关节炎和JIA相关性葡萄膜炎的首选药物，然而，约三分之一的患者对MTX的反应不足。目前的项目集中在单核细胞在这种疾病实体中的作用，试图确定发病机制，特别是研究这种细胞类型在介导MTX治疗的临床反应中的作用。我们试图确定全身治疗反应的生物标志物，为了改进治疗策略和选择MTX治疗的患者，工作计划包括对合并或不合并葡萄膜炎的JIA患者外周血单核细胞和T细胞的表型和功能分析，以及细胞因子和其他生物标志物的分析。通过比较未经治疗的患者和年龄匹配的健康对照组的样本，我们希望获得关于疾病早期的病理生理机制的信息。对MTX系统治疗前和治疗期间的连续样本进行分析，可能会发现对治疗有良好反应的患者和无反应的患者之间的差异。

Juvenile idiopathic arthritis (JIA) is the most frequent rheumatic disease of childhood. Ocular involvement manifesting as anterior uveitis is frequent, especially in children with oligoarticular subtype of arthritis. Methotrexate (MTX) is the first-line treatment of choice for both arthritis as well as JIA-associated uveitis, however, response is insufficient in about one third of patients.The current project focuses on the role of monocytes in this disease entity, seeking to identify disease mechanisms and investigating especially the role of this cell type in mediating clinical response to MTX-treatment.We seek to identify biomarkers for response to systemic treatment, aiming at improvement of therapeutic strategies and selection of patients for treatment with MTX.The work programme encompasses phenotypic and functional analyses of peripher blood monocytes and T cells as well as cytokines and other biomarkers in serum samples of patients with JIA with or without uveitis.By comparing samples of untreated patients and of healthy age-matched controls we hope to obtain information about the pathophysiologic mechanisms in early stages of disease. The analysis of consecutive samples of individuals before and during systemic treatment with MTX might reveal differences between patient with favourable response to treatment and those who are non-responders.