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性疾病。以前葡萄膜炎为表现的眼部受累是常见的，特别是在患有少关节型关节炎的儿童中。甲氨蝶呤（MTX）是关节炎和JIA相关性葡萄膜炎的一线治疗选择，然而，约三分之一的患者反应不足。当前项目的重点是单核细胞在这种疾病实体中的作用，寻求确定疾病机制，特别是研究这种细胞类型在介导对MTX的临床反应中的作用，治疗。我们寻求鉴定对系统治疗反应的生物标志物，目的是改进治疗策略和选择MTX治疗的患者。工作计划包括外周血单核细胞和T细胞以及血清中细胞因子和其他生物标志物的表型和功能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，我们希望获得有关疾病早期病理生理机制的信息。在MTX全身治疗之前和期间对个体的连续样本进行分析可能揭示对治疗有有利反应的患者与无反应者之间的差异。

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.