Segal Barbara M, Nazmul-Hossain Abu N M, Patel Ketan, Hughes Pamela, Moser Kathy L, Rhodus Nelson L
Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011 Jun;111(6):673-80. doi: 10.1016/j.tripleo.2011.01.040. Epub 2011 Apr 16.
Although the key inciting events that drive the progression from autoantibodies to clinical disease remain to be clarified, new light has been shed on the factors contributing to disease susceptibility and the role of genetic factors in determining Sjögren's syndrome (SS) disease phenotypes. The purpose of this article is to provide an update on the role of genetic markers in the susceptibility to and pathogenesis of SS. This article also discusses how genomic and proteomic technology can help in the design of specific therapeutics.
Recent evidence suggests that inflammatory genes associated with interferon pathways, and specific regulatory genes that control the maturation and proliferation of B cells, contribute to the pathogenesis of SS. Both gene expression profiling technology and gene association studies have been used to identify these key biological pathways. Molecularly, defined subsets of pSS patients are also being revealed by these studies. Previously, identified gene loci that predispose to multiple autoimmune disorders have been confirmed supporting the paradigm of "general" autoimmune disease genes. Association of SS with many additional susceptibility loci are likely to be established through ongoing genome-wide association scans (GWAS). Clues from genetic studies suggest that targeting B cells will prove to be an effective way of reducing the systemic manifestations of pSS and are supported by early clinical trials.
Genome-wide technologies are likely to identify new genes and molecular pathways in the pathogenesis of SS that will be useful not only to identify patients at risk for SS, but also to identify subsets of patients at risk for variable levels of disease severity. In the future, these studies could identify novel biomarkers that will lead to significant advances in management by providing the means to tailor therapeutic strategies to individual patients.
尽管促使自身抗体发展为临床疾病的关键诱发事件仍有待阐明，但关于疾病易感性的影响因素以及遗传因素在干燥综合征（SS）疾病表型决定中的作用，已有了新的认识。本文旨在就遗传标志物在SS易感性和发病机制中的作用提供最新信息。本文还将讨论基因组学和蛋白质组学技术如何有助于设计特定的治疗方法。
最近的证据表明，与干扰素途径相关的炎症基因以及控制B细胞成熟和增殖的特定调节基因，在SS发病机制中起作用。基因表达谱技术和基因关联研究都已用于确定这些关键的生物学途径。这些研究还从分子层面揭示了原发性干燥综合征（pSS）患者的特定亚组。此前已确定的易患多种自身免疫性疾病的基因位点得到了证实，支持了“普遍”自身免疫性疾病基因的模式。通过正在进行的全基因组关联扫描（GWAS），可能会确定SS与许多其他易感基因位点的关联。遗传研究的线索表明，靶向B细胞将被证明是减轻pSS全身表现的有效方法，早期临床试验也支持这一点。
全基因组技术可能会在SS发病机制中识别出新的基因和分子途径，这不仅有助于识别SS风险患者，还能识别出疾病严重程度不同的风险患者亚组。未来，这些研究可能会识别出新的生物标志物，通过为个体患者量身定制治疗策略，在疾病管理方面取得重大进展。
