A comprehensive clinical and experimental approach to personalized molecular medicine in patients with defined and undefined autoinflammatory disorders

系统性自身炎症性疾病（SAID）是越来越多的单基因和多因子疾病，继发于先天性免疫反应控制机制的解除，以无菌炎症为特征。到目前为止，正式的诊断标准仅针对少数SAID，但其准确性尚未在不同年龄和人群中得到证实。尽管我们对saaids的分子机制的了解越来越多，但仍有大量个体在临床诊断中没有已知的致病基因突变。该项目包括三个基本组成部分：1)具有良好特征的有价值的患者材料，2)最新的基因组方法，3)整合不同的功能检测方法，以鉴定可能参与saaids发病机制的新的细胞内通路。这将使目前的项目成为最有希望的方法，用于鉴定遗传孤儿SAID患者的因果DNA变异，新基因和生物标志物，以及更有效治疗（个性化医疗）的新可能靶点。

Systemic AutoInflammatory Diseases (SAID) are a growing number of monogenic and multifactorial conditions secondary to deregulation of mechanisms controlling innate immune responses and characterized by sterile inflammation. So far, formal diagnostic criteria have been developed only for a few SAID, but their accuracy has not been confirmed in different ages and populations. In spite of our increasing understanding of the molecular mechanisms of SAIDs, there is still a large number of individuals with a clinical diagnosis but without mutations in known disease causing genes. This project includes three essential ingredients: i) well-characterized valuable patient material, ii) a state of the art genomic approach and iii) integration of different functional assays for the identification of novel intracellular pathways possibly involved in the pathogenesis of SAIDs. This is going to make the present project the most promising approach for the identification of causal DNA variants, new genes and biomarkers in genetically orphan SAID patients, and novel possible targets for more effective treatments (personalized medicine).