Werlein Christopher, Ackermann Max, Hoffmann Thia Leandra, Laenger Florian, Jonigk Danny
Institut für Pathologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, OE 5110, 30625, Hannover, Deutschland.
Institut für Pathologie und Molekularpathologie, Helios Universitätsklinikum Wuppertal, Universität Witten-Herdecke, Wuppertal, Deutschland.
Pathologe. 2021 Feb;42(1):17-24. doi: 10.1007/s00292-020-00898-2. Epub 2021 Jan 8.
Transplantation of solid organs and hematopoietic stem cells represents an important therapeutic option for a variety of end-stage pulmonary diseases, aggressive hematopoietic neoplasms, or severe immunodeficiencies. Although the overall survival following transplantation has generally improved over recent decades, long-time survival of lung and stem-cell transplant recipients is still alarmingly low with an average 5‑year survival rate of only 50-60%. Chronic allo-immunoreactions in general and pulmonary allo-immunoreactions with subsequent fibrosis in particular are major reasons for this poor outcome. Comparable patterns of fibrotic lung remodeling are observed following both lung and hematopoietic stem-cell transplantation. Besides the meanwhile well-established obliterative and functionally obstructive remodeling of the small airways - obliterative bronchiolitis - a specific restrictive subform of fibrosis, namely alveolar fibroelastosis, has been identified. Despite their crucial impact on patient outcome, both entities can be very challenging to detect by conventional histopathological analysis. Their underlying mechanisms are considered overreaching aberrant repair attempts to acute lung injuries with overactivation of (myo-) fibroblasts and excessive and irreversible deposition of extracellular matrix. Of note, the underlying molecular mechanisms are widely divergent between these two morphological entities and are independent of the underlying clinical setting.Further comprehensive investigations of these fibrotic alterations are key to the development of much-needed predictive diagnostics and curative concepts, considering the high mortality of pulmonary fibrosis following transplantation.
实体器官和造血干细胞移植是多种终末期肺部疾病、侵袭性造血系统肿瘤或严重免疫缺陷的重要治疗选择。尽管近几十年来移植后的总体生存率普遍有所提高,但肺移植和干细胞移植受者的长期生存率仍然低得惊人,平均5年生存率仅为50%-60%。一般的慢性同种免疫反应,尤其是随后伴有纤维化的肺部同种免疫反应,是导致这种不良结果的主要原因。在肺移植和造血干细胞移植后均观察到类似的肺纤维化重塑模式。除了目前已明确的小气道闭塞性和功能性阻塞性重塑——闭塞性细支气管炎外,还发现了一种特殊的限制性纤维化亚型,即肺泡纤维弹性组织增生症。尽管它们对患者的预后有至关重要的影响,但通过传统的组织病理学分析很难检测到这两种情况。它们的潜在机制被认为是对急性肺损伤的过度异常修复尝试,伴有(肌)成纤维细胞过度激活以及细胞外基质过度且不可逆的沉积。值得注意的是,这两种形态学实体的潜在分子机制差异很大,且与潜在的临床背景无关。考虑到移植后肺纤维化的高死亡率,对这些纤维化改变进行进一步全面研究是开发急需的预测性诊断方法和治疗方案的关键。