Effect of infliximab on mRNA expression profiles in synovial tissue of rheumatoid arthritis patients.
Effect of infliximab on mRNA expression profiles in synovial tissue of rheumatoid arthritis patients.
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英夫利昔单抗对类风湿关节炎患者滑膜组织 mRNA 表达谱的影响。
DOI：
10.1186/ar2090
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发表时间：
2006
影响因子：
4.9
通讯作者：
Lundeberg, Joakim
中科院分区：
文献类型：
--
作者：
Lindberg, Johan;af Klint, Erik;Catrina, Anca Irinel;Nilsson, Peter;Klareskog, Lars;Ulfgren, Ann-Kristin;Lundeberg, Joakim
我们检查了10例类风湿性关节炎患者接受英夫利西单抗TNF治疗前后关节镜活检的基因表达谱，以研究这些基因表达谱是否可用于预测治疗反应，并研究治疗对基因表达谱的影响。使用欧洲抗风湿联盟反应标准评估对治疗的反应。发现3名患者为良好反应者，5名患者为中度反应者，2名患者为无反应者。还对治疗前每例患者活检组织的TNF-α状态进行了免疫化学研究，并在4例患者的活检组织中检测到TNF-α，包括所有3例良好反应者。基因表达数据表明，所有患者都有独特的基因表达特征，活检之间的患者内变异性较低。数据还揭示了良好反应和无反应患者之间的显著差异（检测到279个差异表达基因，错误发现率< 0.025）。在鉴定的基因中，我们发现MMP-3在良好应答者中显著上调（log 2倍数变化，2.95），与无应答者相比，这进一步支持MMP-3作为对治疗的良好应答的标志物的潜力。在发现TNF-α的患者和无应答者之间发现了685个显著差异表达基因的更广泛列表，表明TNF-α可能是成功英夫利西单抗治疗的重要生物标志物。在抗TNF治疗前后的活检中也观察到了显著差异，包括良好反应组中的115个差异表达基因。有趣的是，在治疗前用化学方法检测TNF-α的组中，这种作用甚至更强。在这里，1,058个基因差异表达，包括许多在这种情况下是新的（例如，CXCL 3和CXCL 14）。随后的基因本体分析显示，已知在炎症组织中受抗TNF治疗影响的几个“主题”显著过度表达;例如，免疫应答（GO：0006955）、细胞通讯（GO：0007154）、信号转导（GO：0007165）和趋化性（GO：0006935）。在中度反应或无反应组中没有基因达到统计学显著性。总之，这项初步研究表明，滑膜组织的基因表达谱的有用性，以预测和监测类风湿关节炎治疗的结果，需要进一步调查。
We examined the gene expression profiles in arthroscopic biopsies retrieved from 10 rheumatoid arthritis patients before and after anti-TNF treatment with infliximab to investigate whether such profiles can be used to predict responses to the therapy, and to study effects of the therapy on the profiles. Responses to treatment were assessed using European League Against Rheumatism response criteria. Three patients were found to be good responders, five patients to be moderate responders and two patients to be nonresponders. The TNF-α status of the biopsies from each of the patients before treatment was also investigated immunohistochemically, and it was detected in biopsies from four of the patients, including all three of the good responders. The gene expression data demonstrate that all patients had unique gene expression signatures, with low intrapatient variability between biopsies. The data also revealed significant differences between the good responding and nonresponding patients (279 differentially expressed genes were detected, with a false discovery rate < 0.025). Among the identified genes we found that MMP-3 was significantly upregulated in good responders (log2 fold change, 2.95) compared with nonresponders, providing further support for the potential of MMP-3 as a marker for good responses to therapy. An even more extensive list of 685 significantly differentially expressed genes was found between patients in whom TNF-α was found and nonresponders, indicating that TNF-α could be an important biomarker for successful infliximab treatment. Significant differences were also observed between biopsies taken before and after anti-TNF treatment, including 115 differentially expressed genes in the good responding group. Interestingly, the effect was even stronger in the group in which TNF-α was immunohistochemically detected before therapy. Here, 1,058 genes were differentially expressed, including many that were novel in this context (for example, CXCL3 and CXCL14). Subsequent Gene Ontology analysis revealed that several 'themes' were significantly over-represented that are known to be affected by anti-TNF treatment in inflammatory tissue; for example, immune response (GO:0006955), cell communication (GO:0007154), signal transduction (GO:0007165) and chemotaxis (GO:0006935). No genes reached statistical significance in the moderately responding or nonresponding groups. In conclusion, this pilot study suggests that further investigation is warranted on the usefulness of gene expression profiling of synovial tissue to predict and monitor the outcome of rheumatoid arthritis therapies.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
5.5
作者：
Catrina, AI;Lampa, J;Ulfgren, AK
通讯作者：
Ulfgren, AK
影响因子：
5
作者：
Batliwalla, FM;Baechler, EC;Gregersen, PK
通讯作者：
Gregersen, PK
影响因子：
4.9
作者：
Jongbloed, SL;Lebre, MC;McInnes, IB
通讯作者：
McInnes, IB
影响因子：
168.9
作者：
Klareskog, L;van der Heijde, D;Sanda, M
通讯作者：
Sanda, M