ARD:对系统性硬化症中纵向皮肤基因表达的大规模分析

2022-03-22 MedSci原创 MedSci原创

系统性硬化症 (SSc) 患者皮肤厚度与免疫细胞和成纤维细胞基因表达失调有关。在早期弥漫性SSc 中,皮肤基因表达随时间而变化,并趋于正常化。

    目的:系统性硬化症 (SSc) 患者的皮肤基因表达失调,但存在异质性。临床疾病特征与皮肤基因表达之间的关系尚未完全确定,并且个人体内皮肤基因表达随时间变化的程度尚不清楚。该研究目的在于确定皮肤基因表达与SSc临床疾病特征之间的关系,以及皮肤基因表达随时间的变化。

    方法:113SSc患者和44名匹配的健康对照中获得总共339份前臂皮肤活检。 105 SSc 患者进行了第二次活检,76 名进行了第三次活检。进行了全局基因表达谱分析,并评估了SSc中差异表达的基因和细胞类型特异性特征与改良的Rodnan皮肤评分 (mRSS) 和其他临床变量的关系。通过混合效应模型和主成分分析分析皮肤基因表达随时间的变化。进行免疫组织化学染色以验证结论。

     结果:SSc患者受累皮肤的基因表达失调比未受累皮肤的患者更严重。免疫细胞和成纤维细胞特征与 mRSS 呈正相关。随着时间的推移,高基线免疫细胞和成纤维细胞特征预测更高的mRSS,但在调整基线mRSS后不能独立预测纵向 mRSS在早期弥漫性皮肤 SSc中,免疫细胞和成纤维细胞特征随时间下降,整体皮肤基因表达趋于正常化。在免疫组织化学染色中,大多数具有高基线T细胞和巨噬细胞数量的早期弥漫性皮肤SSc患者在随访时这些数量有所下降。

     结论:SSc皮肤厚度与免疫细胞和成纤维细胞基因表达失调有关。在早期弥漫性SSc 中,皮肤基因表达随时间而变化,并趋于正常化。这些观察结果与了解 SSc 发病机制相关,可以为治疗策略和临床试验设计提供信息。

 

 

出处:Skaug B, Lyons MA, Swindell WR, et al. Large-scale analysis of longitudinal skin gene expression in systemic sclerosis reveals relationships of immune cell and fibroblast activity with skin thickness and a trend towards normalisation over time. Annals of the Rheumatic Diseases 2022;81:516-523.

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    2022-08-23 ylz8403
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