化脓性汗腺炎的临床与分子特征:新型治疗靶点的实用框架。
Clinical and Molecular Characterization of Hidradenitis Suppurativa: A Practical Framework for Novel Therapeutic Targets.
机构信息
Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Institute for Maternal and Child Health - IRCCS "Burlo Garofolo,", Trieste, Italy.
出版信息
Dermatology. 2023;239(5):836-839. doi: 10.1159/000531496. Epub 2023 Jun 10.
BACKGROUND
The pathophysiological picture underlying hidradenitis suppurativa (HS) and its syndromic forms is still patchy, thus presenting a great challenge for dermatologists and researchers since just by better understanding the pathogenesis of disease we could identify novel therapeutic targets.
METHODS
We propose a practical framework to improve subcategorization of HS patients and support the genotype-phenotype correlation, useful for endotype-directed therapies development.
RESULTS
This framework includes (i) clinical work-up that involves the collection of demographic, lifestyle, and clinical data as well as the collection of different biological samples; (ii) genetic-molecular work-up, based on multi-omics analysis in combination with bioinformatics pipelines to unravel the complex etiology of HS and its syndromic forms; (iii) functional studies, - represented by skin fibroblast cell cultures, reconstructed epidermal models (both 2D and 3D) and organoids -, of candidate biomarkers and genetic findings necessary to validate novel potential molecular mechanisms possibly involved and druggable in HS; (iv) genotype-phenotype correlation and clinical translation in tailored targeted therapies.
CONCLUSION
Omic findings should be merged and integrated with clinical data; moreover, the skin-omic profiles from each HS patient should be matched and integrated with the ones already reported in public repositories, supporting the efforts of the researchers and clinicians to discover novel biomarkers and molecular pathways with the ultimate goal of providing faster development of novel patient-tailored therapeutic approaches.
背景
化脓性汗腺炎(HS)及其综合征形式的病理生理图片仍然不完整,这对皮肤科医生和研究人员来说是一个巨大的挑战,因为只有更好地了解疾病的发病机制,我们才能确定新的治疗靶点。
方法
我们提出了一个实用的框架,以改善 HS 患者的细分,并支持基因型-表型相关性,这对表型定向治疗的发展很有用。
结果
该框架包括(i)临床评估,包括收集人口统计学、生活方式和临床数据以及收集不同的生物样本;(ii)遗传-分子评估,基于多组学分析,结合生物信息学管道,以揭示 HS 及其综合征形式的复杂病因;(iii)功能研究,代表候选生物标志物和遗传发现的皮肤成纤维细胞培养、重建的表皮模型(二维和三维)和类器官,以验证可能涉及的新的潜在分子机制,并在 HS 中进行药物治疗;(iv)基因型-表型相关性和针对特定治疗的临床转化。
结论
应该合并和整合组学发现与临床数据;此外,每个 HS 患者的皮肤组学图谱应该与已经在公共存储库中报告的图谱相匹配和整合,这支持了研究人员和临床医生的努力,以发现新的生物标志物和分子途径,最终目标是为新的患者量身定制的治疗方法提供更快的发展。