Transcriptomic Analysis Identifies Disease Severity and Therapeutic Response in Psoriasis

Sneha Shrotri , Andrea Daamen , Kathryn Kingsmore , Prathyusha Bachali , Amrie Grammer , Peter Lipsky
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Abstract

Abnormalities in gene expression profiles characterize patients with inflammatory skin diseases, including psoriasis, and changes may reflect the action of specific therapeutic agents. To examine this, gene expression analysis of psoriatic skin was assessed by Gene Set Variation Analysis using informative gene modules, and longitudinal data were analyzed to assess the impact of various treatments. Ridge penalized logistic regression was employed to derive a transcriptomic score. Psoriatic lesional skin exhibited perturbations in gene expression profiles at baseline, with enrichment of signatures for neutrophils, keratinocytes, IFN, IL-12 complex, IL-1 cytokines, TNF, and T helper 17. Treatment with a variety of agents reduced lesional gene expression abnormalities to those in nonlesional skin. Specific gene expression abnormalities at baseline identified clinical responders to each treatment. Changes in gene expression over time were less pronounced in nonlesional skin and lesional skin in clinical nonresponders. The combined transcriptomic scores showed significant positive correlations with PASI scores in clinical responders over time. Overall, gene expression abnormalities characterize the severity of psoriatic skin lesions, can be used to predict responsiveness to individual treatments, and revert toward those of nonlesional skin with effective therapy. Therefore, gene expression analysis can be useful to support management of patients with psoriasis.
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转录组学分析确定银屑病的疾病严重程度和治疗反应。
基因表达谱异常是炎症性皮肤病(包括牛皮癣)患者的特征,其变化可能反映了特定治疗剂的作用。为了检验这一点,使用信息性基因模块的基因集变异分析评估了银屑病皮肤的基因表达分析,并分析了纵向数据以评估各种治疗的影响。采用Ridge惩罚逻辑回归得到转录组评分。银屑病皮损皮肤在基线时表现出基因表达谱的扰动,中性粒细胞、角质形成细胞、IFN、IL-12复合物、IL-1细胞因子、TNF和T辅助因子17的特征丰富。用多种药物治疗可以减少病变皮肤的基因表达异常。基线特异性基因表达异常确定了对每种治疗的临床反应。基因表达随时间的变化在非病变皮肤和临床无反应的病变皮肤中不太明显。随着时间的推移,临床应答者的综合转录组评分与PASI评分呈显著正相关。总的来说,基因表达异常表征了银屑病皮肤病变的严重程度,可以用来预测对个体治疗的反应,并在有效治疗后恢复到非病变皮肤。因此,基因表达分析可用于支持银屑病患者的管理。
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审稿时长
8 weeks
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