Deng Jingwen, Leijten Emmerik, Zhu Yongzhan, Nordkamp Michel Olde, Ye Shuyan, Pouw Juliëtte, Tao Weiyang, Balak Deepak, Zheng Guangjuan, Radstake Timothy, Han Ling, Borghans José A M, Lu Chuanjian, Pandit Aridaman
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
J Dermatol Sci. 2023 Sep;111(3):101-108. doi: 10.1016/j.jdermsci.2023.07.005. Epub 2023 Jul 20.
Psoriasis is an immune-mediated inflammatory skin disease. Psoriasis severity evaluation is important for clinicians in the assessment of disease severity and subsequent clinical decision making. However, no objective biomarker is available for accurately evaluating disease severity in psoriasis.
To define and compare biomarkers of disease severity and progression in psoriatic skin.
We performed proteome profiling to study the proteins circulating in the serum from patients with psoriasis, psoriatic arthritis and ankylosing spondylitis, and transcriptome sequencing to investigate the gene expression in skin from the same cohort. We then used machine learning approaches to evaluate different biomarker candidates across several independent cohorts. In order to reveal the cell-type specificity of different biomarkers, we also analyzed a single-cell dataset of skin samples. In-situ staining was applied for the validation of biomarker expression.
We identified that the peptidase inhibitor 3 (PI3) was significantly correlated with the corresponding local skin gene expression, and was associated with disease severity. We applied machine learning methods to confirm that PI3 was an effective psoriasis classifier, Finally, we validated PI3 as psoriasis biomarker using in-situ staining and public datasets. Single-cell data and in-situ staining indicated that PI3 was specifically highly expressed in keratinocytes from psoriatic lesions.
Our results suggest that PI3 may be a psoriasis-specific biomarker for disease severity and hyper-keratinization.
银屑病是一种免疫介导的炎症性皮肤病。银屑病严重程度评估对于临床医生评估疾病严重程度及后续临床决策至关重要。然而，目前尚无客观生物标志物可用于准确评估银屑病的疾病严重程度。
定义并比较银屑病皮肤中疾病严重程度和进展的生物标志物。
我们进行了蛋白质组分析，以研究银屑病、银屑病关节炎和强直性脊柱炎患者血清中循环的蛋白质，并进行转录组测序，以研究同一队列皮肤中的基因表达。然后，我们使用机器学习方法在几个独立队列中评估不同的生物标志物候选物。为了揭示不同生物标志物的细胞类型特异性，我们还分析了皮肤样本的单细胞数据集。采用原位染色验证生物标志物表达。
我们发现肽酶抑制剂3（PI3）与相应的局部皮肤基因表达显著相关，并与疾病严重程度相关。我们应用机器学习方法证实PI3是一种有效的银屑病分类器，最后，我们使用原位染色和公共数据集验证PI3为银屑病生物标志物。单细胞数据和原位染色表明，PI3在银屑病皮损的角质形成细胞中特异性高表达。
我们的结果表明，PI3可能是一种用于疾病严重程度和过度角化的银屑病特异性生物标志物。
