D'Ovidio Frank, Floros Joanna, Aramini Beatrice, Lederer David, DiAngelo Susan L, Arcasoy Selim, Sonett Joshua R, Robbins Hillary, Shah Lory, Costa Joseph, Urso Andreacarola
Division of Thoracic Surgery, Lung Transplant Program, Columbia University Medical Center, New York, NY, USA
Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
Eur Respir J. 2020 Mar 5;55(3). doi: 10.1183/13993003.00618-2019. Print 2020 Mar.
Gene polymorphisms of surfactant proteins, key players in lung innate immunity, have been associated with various lung diseases. The aim of this study was to investigate the potential association between variations within the surfactant protein (SP)-A gene of the donor lung allograft and recipient post-transplant outcome.
Lung-transplant patients (n=192) were prospectively followed-up with pulmonary function tests, bronchoscopies with bronchoalveolar lavage and biopsies. Donor lungs were assayed for SP-A1 (6A) and SP-A2 (1A) gene polymorphism using the pyrosequencing method. Unadjusted and adjusted stratified Cox survival models are reported.
SP-A1 and SP-A2 genotype frequency and lung transplant recipient and donor characteristics as well as cause of death are noted. Recipients were grouped per donor SP-A2 variants. Individuals that received lungs from donors with the SP-A2 1A (n=102) 1A variant (n=68) or SP-A2 genotype 1A1A (n=54) 1AA (n=38) had greater survival at 1 year (log-rank p<0.025). No significant association was noted for SP-A1 variants. Stratified adjusted survival models for 1-year survival and diagnosis showed a reduced survival for 1A variant and the 1A1A genotype. Furthermore, when survival was conditional on 1-year survival no significance was observed, indicating that the survival difference was due to the first year's outcome associated with the 1A variant.
Donor lung SP-A gene polymorphisms are associated with post-transplant clinical outcome. Lungs from donors with the SP-A2 variant 1A had a reduced survival at 1 year. The observed donor genetic differences, innate immunity relate to the post-transplant clinical outcome.
表面活性蛋白是肺固有免疫的关键参与者，其基因多态性与多种肺部疾病有关。本研究旨在探讨供体肺移植中表面活性蛋白（SP）-A基因变异与受体移植后结局之间的潜在关联。
对192例肺移植患者进行前瞻性随访，包括肺功能测试、支气管肺泡灌洗和活检的支气管镜检查。采用焦磷酸测序法检测供体肺的SP-A1（6A）和SP-A2（1A）基因多态性。报告了未调整和调整后的分层Cox生存模型。
记录了SP-A1和SP-A2基因型频率、肺移植受体和供体特征以及死亡原因。根据供体SP-A2变异对受体进行分组。接受携带SP-A2 1A（n = 102）1A变异（n = 68）或SP-A2基因型1A1A（n = 54）1AA（n = 38）供体肺的个体在1年时具有更高的生存率（对数秩检验p<0.025）。未发现SP-A1变异有显著关联。1年生存率和诊断的分层调整生存模型显示1A变异和1A1A基因型的生存率降低。此外，当生存以1年生存率为条件时未观察到显著性，表明生存差异是由于与1A变异相关的第一年结局所致。
供体肺SP-A基因多态性与移植后临床结局相关。携带SP-A2变异1A的供体肺在1年时生存率降低。观察到的供体基因差异，即固有免疫，与移植后临床结局相关。
