Division of Paediatric Rheumatology, Department of Paediatrics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
Department of Paediatric Rheumatology, Sanliurfa Training and Research Hospital, Sanliurfa, Turkey.
Front Immunol. 2019 Dec 17;10:2813. doi: 10.3389/fimmu.2019.02813. eCollection 2019.
Precision medicine (PM) is an emerging data-driven health care approach that integrates phenotypic, genomic, epigenetic, and environmental factors unique to an individual. The goal of PM is to facilitate diagnosis, predict effective therapy, and avoid adverse reactions specific for each patient. The forefront of PM is in oncology; nonetheless, it is developing in other fields of medicine, including rheumatology. Recent studies on elucidating the genetic architecture of polygenic and monogenic rheumatological diseases have made PM possible by enabling physicians to customize medical treatment through the incorporation of clinical features and genetic data. For complex inflammatory disorders, the prevailing paradigm is that disease susceptibility is due to additive effects of common reduced-penetrance gene variants and environmental factors. Efforts have been made to calculate cumulative genetic risk score (GRS) and to relate specific susceptibility alleles for use of target therapies. The discovery of rare patients with single-gene high-penetrance mutations informed our understanding of pathways driving systemic inflammation. Here, we review the advances in practicing PM in patients with primary systemic vasculitides (PSVs). We summarize recent genetic studies and discuss current knowledge on the contribution of epigenetic factors and extracellular vesicles (EVs) in disease progression and treatment response. Implementation of PM in PSVs is a developing field that will require analysis of a large cohort of patients to validate data from genomics, transcriptomics, metabolomics, proteomics, and epigenomics studies for accurate disease profiling. This multi-omics approach to study disease pathogeneses should ultimately provide a powerful tool for stratification of patients to receive tailored optimal therapies and for monitoring their disease activity.
精准医学（PM）是一种新兴的数据驱动型医疗保健方法，它整合了个体特有的表型、基因组、表观基因组和环境因素。PM 的目标是促进诊断、预测有效治疗方法，并避免每个患者的不良反应。PM 的前沿领域是肿瘤学；然而，它也在其他医学领域发展，包括风湿病学。最近关于阐明多基因和单基因风湿性疾病遗传结构的研究使 PM 成为可能，使医生能够通过整合临床特征和遗传数据来定制医疗。对于复杂的炎症性疾病，流行的范式是疾病易感性是由于常见的低外显率基因变异和环境因素的累加效应。已经努力计算累积遗传风险评分（GRS），并确定特定的易感等位基因，以用于靶向治疗。罕见的具有单基因高外显率突变的患者的发现使我们对驱动全身炎症的途径有了更深入的了解。在这里，我们回顾了在原发性系统性血管炎（PSV）患者中实施 PM 的进展。我们总结了最近的遗传研究，并讨论了表观遗传因素和细胞外囊泡（EVs）在疾病进展和治疗反应中的作用的当前知识。PM 在 PSV 中的实施是一个正在发展的领域，需要对大量患者进行分析，以验证来自基因组学、转录组学、代谢组学、蛋白质组学和表观基因组学研究的数据，以准确进行疾病分析。这种疾病发病机制的多组学方法最终应该为分层患者以接受量身定制的最佳治疗和监测他们的疾病活动提供强大的工具。
