Department of Advanced Diagnostics, Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", 34137, Trieste, Italy.
Department of Pathology, Federal University of Pernambuco, Recife, 50670-901, Brazil.
Sci Rep. 2023 Mar 25;13(1):4919. doi: 10.1038/s41598-023-31914-z.
Pyoderma gangrenosum (PG) is a rare inflammatory skin disease classified within the spectrum of neutrophilic dermatoses. The pathophysiology of PG is yet incompletely understood but a prominent role of genetics facilitating immune dysregulation has been proposed. This study investigated the potential contribution of disrupted molecular pathways in determining the susceptibility and clinical severity of PG. Variant Enrichment Analysis, a bioinformatic pipeline applicable for Whole Exome Sequencing data was performed in unrelated PG patients. Eleven patients were enrolled, including 5 with unilesional and 6 with multilesional PG. Fourteen pathways were exclusively enriched in the "multilesional" group, mainly related to immune system (i.e., type I interferon signaling pathway), cell metabolism and structural functions. In the "unilesional" group, nine pathways were found to be exclusively enriched, mostly related to cell signaling and cell metabolism. Genetically altered pathways involved in immune system biology and wound repair appear to be nodal pathogenic drivers in PG pathogenesis.
坏疽性脓皮病（PG）是一种罕见的炎症性皮肤病，属于中性粒细胞皮肤病谱。PG 的病理生理学尚未完全了解，但已提出遗传易感性促进免疫失调的重要作用。本研究探讨了分子通路紊乱在决定 PG 易感性和临床严重程度方面的潜在作用。在无亲缘关系的 PG 患者中进行了变异富集分析，这是一种适用于全外显子组测序数据的生物信息学分析方法。共纳入 11 名患者，其中 5 名患有单发性 PG，6 名患有多发性 PG。在“多发性”组中，有 14 条通路是特异性富集的，主要与免疫系统（即 I 型干扰素信号通路）、细胞代谢和结构功能有关。在“单发性”组中，发现有 9 条通路是特异性富集的，主要与细胞信号转导和细胞代谢有关。涉及免疫系统生物学和伤口修复的遗传改变通路似乎是 PG 发病机制中的主要致病驱动因素。
