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首页> 外文期刊>Arthritis and Rheumatism >Gene expression profile in the salivary glands of primary Sj?gren's syndrome patients before and after treatment with rituximab
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Gene expression profile in the salivary glands of primary Sj?gren's syndrome patients before and after treatment with rituximab

机译：利妥昔单抗治疗前后原发性干燥综合征患者唾液腺中的基因表达谱

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Objective. Primary Sj?gren's syndrome (SS) is a complex disorder, in part due to B cell abnormalities. Although anti-B cell therapy is promising in primary SS, no treatment has yet been demonstrated to modify the disease course. This open-label study was undertaken to evaluate the efficacy of rituximab in primary SS and to investigate whether expression of specific genes is associated with efficacy of this treatment. Methods. Fifteen patients with primary SS were treated in an open-label trial. Salivary gland biopsy specimens were obtained, and total RNA was extracted and amplified. Microarray analysis with the Affymetrix Human Genome U133 Plus 2.0 Array was used to analyze >54,000 transcripts, and potential pathways were identified. Results. With gene expression data obtained before treatment, patients could be correctly classified in terms of whether they would be responders or nonresponders to rituximab. Gene pathway analysis demonstrated that the B cell signaling pathway was the most profoundly differentially expressed before treatment in the responders compared with nonresponders. Subclassification of patients based on the level of infiltration also demonstrated differential expression of genes belonging to the interferon (IFN) pathway between responders and nonresponders. Furthermore, unsupervised analysis based on gene expression modification before and after treatment allowed identification of 8 genes that were differentially expressed between responders and nonresponders, with the difference remaining significant after Bonferroni correction. Conclusion. Our results demonstrate the ability to elaborate a set of genes predictive of rituximab efficacy and highlight the importance of studying the differential expression of B cell and IFN pathway signaling molecules in relation to the response to anti-CD20 treatment. A randomized controlled study is currently ongoing to confirm these results.
机译：目的。原发性干燥综合征（SS）是一种复杂的疾病，部分归因于B细胞异常。尽管抗B细胞疗法在原发性SS中很有前途，但尚无疗法可改变病程。这项开放标签研究旨在评估利妥昔单抗在原发性SS中的疗效，并调查特定基因的表达是否与此治疗效果相关。方法。一项开放标签试验治疗了15例原发性SS患者。获得唾液腺活检标本，并提取和扩增总RNA。使用Affymetrix人类基因组U133 Plus 2.0阵列进行的微阵列分析可分析> 54,000个转录本，并确定了潜在的途径。结果。利用治疗前获得的基因表达数据，可以根据患者对利妥昔单抗的反应性或非反应性正确分类患者。基因途径分析表明，与无反应者相比，在反应者中治疗前B细胞信号通路的表达最深刻。根据浸润水平对患者进行亚分类还显示了应答者和非应答者之间属于干扰素（IFN）途径的基因的差异表达。此外，基于治疗前后基因表达修饰的无监督分析可以鉴定应答者和非应答者之间差异表达的8个基因，在Bonferroni校正后差异仍然很明显。结论。我们的结果证明了拟订一组预测利妥昔单抗功效的基因的能力，并强调了研究B细胞和IFN途径信号分子与抗CD20治疗反应相关的差异表达的重要性。目前正在进行一项随机对照研究，以证实这些结果。

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