• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Gene expression profiling in peripheral blood of Sjogren's syndrome patients.
【24h】

Gene expression profiling in peripheral blood of Sjogren's syndrome patients.

机译：干燥综合征患者外周血的基因表达谱分析。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Sjogren's syndrome (SS) is a common autoimmune disorder characterized by lymphocytic infiltration into exocrine glands. Disruption of target organ function, such as salivary and lacrimal glands may lead to irreversible manifestations such as severe dry eyes and mouth. A complex genetic architecture combined with the influence of environmental factors is thought to contribute to the etiology of SS; however, the pathophysiological basis of SS is poorly understood. To identify important molecular pathways involved in SS and define biomarkers for clinical features of the disease, we have used high-density oligonucleotide microarrays to compare global gene expression profiles in peripheral blood samples of SS patients and controls. We first analyzed mononuclear cells of 21 SS patients and 23 controls and identified a prominent pattern of over-expressed genes that are inducible by interferons (IFNs). We then repeated the analysis in whole blood of a second independent dataset of 17 SS patients and 22 controls and observed the same pattern with respect to IFN inducible genes. Furthermore, we observed that gene expression of IFN-inducible genes was positively correlated with titers of anti-Ro/SSA (P0.001) and anti-La/SSB (P0.001) autoantibodies and negatively correlated to salivary flow or tear production. Additional inflammatory and immune-related pathways with altered expression patterns in SS cases included B and T cell receptor, IGF-1, GM-CSF, PPARalpha/RXRalpha, and PI3/AKT signaling. Our results strongly support innate and adaptive immune processes in the pathogenesis of SS and provide numerous candidate disease markers for further study.;We also compared gene expression profiles between patients with SS and systemic lupus erythematosus (SLE). Systemic manifestations in SS patients are common and may include clinical and serological overlap with other autoimmune disease features such as SLE. The pathophysiology of common and distinct features of SS and SLE are poorly understood. In this section of the study, we have directly compared gene expression profiles in whole blood of SS patients and SLE patients to determine which genes are differentially expressed in both phenotypes, and which genes distinguish the two patient groups. Approximately 22,000 RNA transcripts were interrogated using the Affymetrix U133A GeneChip RTM. Differentially expressed genes were defined using t-tests with nominal significance of p0.001 and average fold change of >1.5. Our gene expression datasets included 35 Caucasian female SLE patients, 36 Caucasian female SS patients, and 62 Caucasian female controls. We compared each group of SS (n=36) and SLE (n=35) patients separately to the 62 controls. A total of 349 genes were differentially expressed in SS patients and 625 genes were differentially expressed in SLE patients. Of these two gene lists, 95 genes overlapped and were differentially expressed in both SS and SLE patients, the majority of which are IFN-inducible. Among the non-overlapping genes, ribosomal proteins were highly overexpressed in SLE patients but underexpressed in SS patients relative to controls. These results show that SS and SLE patients have identifiable gene expression signatures that are either common or distinct between the two patient populations. Characterization of these profiles has significant potential to facilitate development of improved diagnostic approaches and targeted therapies.
机译：干燥综合征（SS）是一种常见的自身免疫性疾病，其特征是淋巴细胞浸入外分泌腺。靶器官功能（例如唾液和泪腺）的破坏可能导致不可逆的表现，例如严重的口干眼症。复杂的遗传结构加上环境因素的影响被认为是SS的病因。然而，对SS的病理生理基础了解甚少。为了鉴定参与SS的重要分子途径并确定该疾病临床特征的生物标志物，我们使用了高密度寡核苷酸微阵列来比较SS患者和对照患者外周血中的整体基因表达谱。我们首先分析了21名SS患者和23名对照的单核细胞，并确定了干扰素（IFN）诱导的过度表达基因的突出模式。然后，我们在全血中重复分析了17名SS患者和22名对照的第二个独立数据集，并观察到关于IFN诱导型基因的相同模式。此外，我们观察到IFN诱导型基因的基因表达与抗Ro / SSA（P <0.001）和抗La / SSB（P <0.001）自身抗体的滴度呈正相关，与唾液流动或泪液产生呈负相关。 SS病例中表达模式改变的其他炎症和免疫相关途径包括B和T细胞受体，IGF-1，GM-CSF，PPARalpha / RXRalpha和PI3 / AKT信号传导。我们的结果有力地支持了SS发病过程中的先天性和适应性免疫过程，并为进一步研究提供了多种候选疾病标记。我们还比较了SS患者和系统性红斑狼疮（SLE）患者之间的基因表达谱。 SS患者的全身表现很常见，可能包括与其他自身免疫性疾病特征（如SLE）的临床和血清学重叠。对SS和SLE的共同特征和独特特征的病理生理了解甚少。在本研究的这一部分中，我们直接比较了SS患者和SLE患者全血中的基因表达谱，以确定哪些基因在两种表型中差异表达，以及哪些基因区分了两个患者组。使用Affymetrix U133A GeneChip RTM查询大约22,000个RNA转录本。使用t检验定义差异表达的基因，其名义显着性为p <0.001，平均倍数变化> 1.5。我们的基因表达数据集包括35名白种女性SLE患者，36名白种女性SS患者和62名白种女性对照。我们分别将每组SS（n = 36）和SLE（n = 35）患者与62个对照组进行了比较。在SS患者中总共349个基因差异表达，在SLE患者中625个基因差异表达。在这两个基因列表中，有95个基因重叠并在SS和SLE患者中差异表达，其中大多数是IFN诱导型的。在非重叠基因中，相对于对照，核糖体蛋白在SLE患者中高度过表达，但在SS患者中表达不足。这些结果表明，SS和SLE患者具有可识别的基因表达特征，在两个患者群体之间相同或不同。这些特征的表征具有巨大的潜力，可促进改进诊断方法和靶向疗法的开发。

著录项

  • 作者

    Emamian, Eshrat Sadat.;

  • 作者单位

    University of Minnesota.;

  • 授予单位 University of Minnesota.;
  • 学科 Biology Genetics.;Health Sciences Dentistry.;Health Sciences Medicine and Surgery.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 113 p.
  • 总页数 113
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号