Division of Nephrology, Dialysis, and Transplantation, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
Schena Foundation, Valenzano, Bari, Italy.
Nephrol Dial Transplant. 2018 Dec 1;33(12):2101-2112. doi: 10.1093/ndt/gfy130.
Immunoglobulin A nephropathy (IgAN) is the most common worldwide primary glomerulonephritis with a strong autoimmune component. The disease shows variability in both clinical phenotypes and endpoints and can be potentially subdivided into more homogeneous subtypes through the identification of specific molecular biomarkers. This review focuses on the role of omics in driving the identification of potential molecular subtypes of the disease through the integration of multilevel data from genomics, transcriptomics, epigenomics, proteomics and metabolomics. First, the identification of molecular biomarkers, including mapping of the full spectrum of common and rare IgAN risk alleles, could permit a more precise stratification of IgAN patients. Second, the analysis of transcriptomic patterns and their modulation by epigenetic factors like microRNAs has the potential to increase our understanding in the pathogenic mechanisms of the disease. Third, the specificity of urinary proteomic and metabolomic signatures and the understanding of their functional relevance may contribute to the development of new non-invasive biomarkers for a better molecular characterization of the renal damage and its follow-up. All these approaches can give information for targeted therapeutic decisions and will support novel clinical decision making. In conclusion, we offer a framework of omic studies and outline barriers and potential solutions that should be used for improving the diagnosis and treatment of the disease. The ongoing decade is exploiting novel high-throughput molecular technologies and computational analyses for improving the diagnosis (precision nephrology) and treatment (personalized therapy) of the IgAN subtypes.
免疫球蛋白 A 肾病 (IgAN) 是全球最常见的原发性肾小球肾炎，具有强烈的自身免疫成分。该疾病在临床表型和终点方面存在变异性，并且可以通过鉴定特定的分子生物标志物潜在地分为更同质的亚型。这篇综述重点介绍了通过整合来自基因组学、转录组学、表观基因组学、蛋白质组学和代谢组学的多层次数据，组学在推动疾病潜在分子亚型鉴定中的作用。首先，分子生物标志物的鉴定，包括常见和罕见 IgAN 风险等位基因的全谱映射，可能会允许对 IgAN 患者进行更精确的分层。其次，转录组模式及其通过 microRNAs 等表观遗传因子的调节的分析有可能增加我们对疾病发病机制的理解。第三，尿蛋白质组学和代谢组学特征的特异性及其功能相关性的理解可能有助于开发新的非侵入性生物标志物，以更好地对肾脏损伤及其随访进行分子特征分析。所有这些方法都可以提供针对特定治疗的决策信息，并支持新的临床决策。总之，我们提供了一个组学研究框架，并概述了应该用于改善疾病诊断和治疗的障碍和潜在解决方案。当前十年正在利用新型高通量分子技术和计算分析来改善 IgAN 亚型的诊断（精准肾病学）和治疗（个性化治疗）。
