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首页> 外文期刊>The Journal of investigative dermatology. >Intrinsic gene expression subsets of diffuse cutaneous systemic sclerosis are stable in serial skin biopsies
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Intrinsic gene expression subsets of diffuse cutaneous systemic sclerosis are stable in serial skin biopsies

机译：在一系列皮肤活检中，弥漫性皮肤系统性硬化的内在基因表达子集是稳定的

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Skin biopsy gene expression was analyzed by DNA microarray from 13 diffuse cutaneous systemic sclerosis (dSSc) patients enrolled in an open-label study of rituximab, 9 dSSc patients not treated with rituximab, and 9 healthy controls. These data recapitulate the patient intrinsic gene expression subsets described previously, including fibroproliferative, inflammatory, and normal-like groups. Serial skin biopsies showed consistent and non-progressing gene expression over time, and importantly, the patients in the inflammatory subset do not move to the fibroproliferative subset, and vice versa. We were unable to detect significant differences in gene expression before and after rituximab treatment, consistent with an apparent lack of clinical response. Serial biopsies from each patient stayed within the same gene expression subset, regardless of treatment regimen or the time point at which they were taken. Collectively, these data emphasize the heterogeneous nature of SSc and demonstrate that the intrinsic subsets are an inherent, reproducible, and stable feature of the disease that is independent of disease duration. Moreover, these data have fundamental importance for the future development of personalized therapy for SSc; drugs targeting inflammation are likely to benefit those patients with an inflammatory signature, whereas drugs targeting fibrosis are likely to benefit those with a fibroproliferative signature.
机译：通过DNA芯片对13例接受利妥昔单抗开放标签研究的弥漫性皮肤系统性硬化症（dSSc）患者，9例未经利妥昔单抗治疗的dSSc患者和9例健康对照组的皮肤活检基因表达进行了分析。这些数据概括了先前描述的患者固有基因表达子集，包括纤维增生，炎性和正常人群。连续的皮肤活检显示随着时间的推移，基因表达始终一致且不进行，重要的是，炎症亚组中的患者不会转移至纤维增生亚组，反之亦然。我们无法检测到利妥昔单抗治疗前后基因表达的显着差异，这与临床反应明显缺乏相符。无论治疗方案或服用时间长短，每位患者的连续活检均位于同一基因表达子集内。总体而言，这些数据强调了SSc的异质性，并证明内在子集是疾病的固有，可再现和稳定的特征，与疾病持续时间无关。而且，这些数据对于SSc个性化治疗的未来发展具有根本的重要性。靶向炎症的药物可能会有益于具有炎症特征的患者，而靶向纤维化的药物可能会使具有纤维增生特征的患者受益。

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