Sellebjerg F, Datta P, Larsen J, Rieneck K, Alsing I, Oturai A, Svejgaard A, Soelberg Sørensen P, Ryder L P
Department of Neurology, Danish Multiple Sclerosis Research Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Mult Scler. 2008 Jun;14(5):615-21. doi: 10.1177/1352458507085976. Epub 2008 Apr 11.
Treatment with interferon-beta (IFN-beta) induces the expression of hundreds of genes in blood mononuclear cells, and the expression of several genes has been proposed as a marker of the effect of treatment with IFN-beta. However, to date no molecules have been identified that are stably induced by treatment with IFN-beta. We use DNA microarrays to study gene expression in 10 multiple sclerosis (MS) patients who began de novo treatment with IFN-beta. After the first injection of IFN-beta, the expression of 74 out of 3428 genes changed at least two-fold and statistically significantly (after Bonferroni correction). In contrast, we observed no persisting effects of IFN-beta on gene expression. Among the most strongly induced genes was MXA, which has been used in previous biomarker studies in MS. In addition, the study identified the induction of LGALS9 and TCIR1G, involved in negative regulation of T helper type I immunity and T-cell activation, as novel effects of IFN-beta therapy in MS.
用β-干扰素(IFN-β)治疗可诱导血液单核细胞中数百种基因的表达,并且已提出几种基因的表达作为IFN-β治疗效果的标志物。然而,迄今为止,尚未鉴定出因IFN-β治疗而被稳定诱导的分子。我们使用DNA微阵列研究10例开始接受IFN-β从头治疗的多发性硬化症(MS)患者的基因表达。首次注射IFN-β后,3428个基因中的74个基因的表达至少改变了两倍且具有统计学意义(经Bonferroni校正)。相比之下,我们未观察到IFN-β对基因表达有持续影响。诱导最强的基因包括MXA,它曾用于MS先前的生物标志物研究。此外,该研究确定,参与I型辅助性T细胞免疫负调控和T细胞活化的LGALS9和TCIR1G的诱导是IFN-β治疗MS的新效应。