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Abstract：
Idiopathic subglottic stenosis (ISGS) is a rare fibrotic disease of the upper trachea with an unknown pathomechanism. It typically affects adult Caucasian female patients, leading to severe airway constrictions caused by progressive scar formation and inflammation with clinical symptoms of dyspnoea, stridor and potential changes to the voice. Endoscopic treatment frequently leads to recurrence, whereas surgical resection and reconstruction provides excellent long-term functional outcome. This study aimed to identify so far unrecognized pathologic aspects of ISGS using single cell RNA sequencing. Our scRNAseq analysis uncovered the cellular composition of the subglottic scar tissue, including the presence of a pathologic, profibrotic fibroblast subtype and the presence of Schwann cells in a profibrotic state. In addition, a pathology-associated increase of plasma cells was identified. Using extended bioinformatics analyses, we decoded pathology-associated changes of factors of the extracellular matrix. Our data identified ongoing fibrotic processes in ISGS and provide novel insights on the contribution of fibroblasts, Schwann cells and plasma cells to the pathogenesis of ISGS. This knowledge could impact the development of novel approaches for diagnosis and therapy of ISGS.
摘要：
特发性声门下狭窄（ISGS）是一种罕见的上气管纤维化疾病，其病理机制未知。它通常影响成年白人女性患者，导致由进行性瘢痕形成和炎症引起的严重气道收缩，并伴有呼吸困难的临床症状，喘鸣和声音的潜在变化。内镜治疗经常导致复发，而手术切除和重建提供了极好的长期功能结果。这项研究旨在使用单细胞RNA测序来鉴定迄今为止尚未识别的ISGS病理方面。我们的scRNAseq分析揭示了声门下瘢痕组织的细胞组成，包括病理的存在，促纤维化成纤维细胞亚型和施万细胞在促纤维化状态的存在。此外,发现与病理学相关的浆细胞增加.使用扩展的生物信息学分析，我们解码了细胞外基质因子的病理相关变化。我们的数据确定了ISGS中正在进行的纤维化过程，并为成纤维细胞的贡献提供了新的见解。雪旺细胞和浆细胞对ISGS的发病机制。这些知识可能会影响ISGS诊断和治疗新方法的开发。
