Blood cell gene expression profiling in rheumatoid arthritis - Discriminative genes and effect of rheumatoid factor
Blood cell gene expression profiling in rheumatoid arthritis - Discriminative genes and effect of rheumatoid factor
复制标题
DOI：
10.1016/j.imlet.2004.03.018
复制
发表时间：
2004-05-15
影响因子：
4.4
通讯作者：
Bendtzen, K
中科院分区：
文献类型：
--
作者：
Bovin, LF;Rieneck, K;Bendtzen, K
为了研究类风湿因子（RF）在类风湿关节炎（RA）中的致病重要性并鉴定患者和健康个体中差异表达的基因，从8名RF阳性和6名RF阴性RA患者以及7名健康对照的外周血单核细胞（PBMC）中分离总RNA。使用基于寡核苷酸的DNA芯片微阵列检测了约10，000个基因的基因表达。分析显示RF阳性和RF阴性患者PBMC表达模式无显著差异。然而，比较所有14例RA患者和健康对照的基因表达模式，发现了一个具有歧视性的基因子集。用真实的时间反转录聚合酶链反应（RT-PCR）对另一组RA患者和健康对照进行了验证。这证实了以下基因在RA患者中的表达显著高于健康对照组：CD 14抗原、防御素α-1和α-3（DEFA）、脂肪酸辅酶A连接酶、长链2（FACL）、核糖核酸酶2（RNASE 2）、S100钙结合蛋白AS和A12（S100 A8和S100 A12）。与此相反，与健康对照组相比，RA患者的MHC II类DQ β 1（HLA-DQB 1）表达显著降低。结论：采用分析方法，我们没有发现任何迹象表明RF阳性和RF阴性RA是两种根本不同的疾病。RA患者和健康个体之间的大多数基因的区别是已知的参与免疫炎症反应，特别是那些有关改变吞噬功能。(C)2004 Elsevier B. V.保留所有权利。
To study the pathogenic importance of the rheumatoid factor (RF) in rheumatoid arthritis (RA) and to identify genes differentially expressed in patients and healthy individuals, total RNA was isolated from peripheral blood mononuclear cells (PBMC) from eight RF-positive and six RF-negative RA patients, and seven healthy controls. Gene expression of about 10,000 genes were examined using oligonucleotide-based DNA chip microarrays.The analyses showed no significant differences in PBMC expression patterns from RF-positive and RF-negative patients. However, comparisons of gene expression patterns from all fourteen RA patients and healthy controls identified a subset of discriminative genes. These results were validated by real time reverse transcription polymerase chain reaction (RT-PCR) on another group of RA patients and healthy controls. This confirmed that the following genes had a significantly higher expression in RA patients than in healthy controls: CD14 antigen, defensin alpha-1 and alpha-3 (DEFA), fatty-acid-Coenzyme A ligase, long-chain 2 (FACL), ribonuclease 2 (RNASE2), S 100 calcium-binding protein AS and A12 (S100A8 and S100A12). In contrast, the expression of MHC class II, DQ beta1 (HLA-DQB1) was significantly reduced in RA patients compared to healthy controls. Conclusions: With the analytical procedure employed, we did not find any indication that RF-positive and RF-negative RA are two fundamentally different diseases. Most of the genes discriminative between RA patients and healthy individuals are known to be involved in immunoinflammatory responses, especially those related to altered phagocytic functions. (C) 2004 Elsevier B.V. All rights reserved.