Development of a urinary biomarker panel and software-based solutions to optimize treatment strategies for Systemic Juvenile Idiopathic Arthritis.

摘要 全身性幼年特发性关节炎（SJIA）是一种罕见的自身炎症性疾病， 长期的滑膜炎症会导致结构性关节损伤。大约15-30% SJIA患者会出现一种称为巨噬细胞活化综合征（MAS）的并发症， 由T细胞沿着巨噬细胞的过度活化和增殖引起。患者 复发性MAS可发展为间质性肺病（LD）， 肺泡巨噬细胞功能障碍引起的肺泡蛋白沉积症。一旦肺部疾病 在SJIA儿童中诊断，57%的患者在两年内死亡， 诊断.识别疾病进展早期发生的异常病理， 为了提高患者的护理标准， 延长病人的生命。Ethos R&D建议开发一种由两部分组成的检测试剂盒，包括 与炎症和非炎症病理学相关的生物标志物， SJIA患者，可通过高效液相色谱法从尿液样本中进行分析 色谱法、串联质谱法（LC-MS/MS）。沿着生物标志物测定， Ethos R&D将根据生物标志物分析开发基于软件的解决方案报告， 将向医生、家长和患者推荐辅助治疗。 通过与CCHMC的临床医生合作，我们将能够确定 通过分析SJIA患者的亚型（活动性SJIA，SJIA伴MAS， SJIA伴肺部疾病）与健康对照（患者同胞）相比。这样的技术 可以为SJIA患者提供改变生活的护理标准。

Abstract Systemic Juvenile Idiopathic Arthritis (SJIA) is a rare, auto-inflammatory condition characterized by prolonged synovial inflammation that can lead to structural joint damage. Roughly 15-30% of SJIA patients develop a complication called macrophage activation syndrome (MAS), which is caused by excessive activation and proliferation of T cells along with macrophages. Patients with recurrent MAS can develop interstitial lung disease (LD) with features of pulmonary alveolar proteinosis caused by dysfunction of alveolar macrophages. Once lung disease is diagnosed in children with SJIA, fatality occurs in 57% of patients within two years of diagnosis. Identifying abnormal pathologies that occur early in disease progression and are specific to subtypes of SJIA is imperative in order to improve the standard of care for patients and prolong patient life. Ethos R&D proposes to develop a 2-part assay, consisting of biomarkers related to inflammatory and non-inflammatory pathologies that are perturbed in patients with SJIA, that can be analyzed from urine samples by high-performance liquid chromatography, tandem mass spectrometry (LC-MS/MS). Along with the biomarker assay, Ethos R&D will develop a software-based solution report according to biomarker analysis that will communicate recommended adjuvant therapies for physicians, parents and patients. Through collaboration with clinicians at CCHMC, we will be able to determine the specificity of a urine-based test panel by analyzing subtypes of patients with SJIA (active SJIA, SJIA with MAS, SJIA with lung disease) as compared to healthy controls (patient siblings). Such a technology could provide life-changing standard of care for SJIA patients.