Lung Transplant Program, Columbia University, New York, NY, USA.
Am J Transplant. 2013 Aug;13(8):2130-6. doi: 10.1111/ajt.12326. Epub 2013 Jul 10.
Chronic lung allograft dysfunction (CLAD) is the major factor limiting long-term success of lung transplantation. Polymorphisms of surfactant protein D (SP-D), an important molecule within lung innate immunity, have been associated with various lung diseases. We investigated the association between donor lung SP-D polymorphisms and posttransplant CLAD and survival in 191 lung transplant recipients consecutively transplanted. Recipients were prospectively followed with routine pulmonary function tests. Donor DNA was assayed by pyrosequencing for SP-D polymorphisms of two single-nucleotide variations altering amino acids in the mature protein N-terminal domain codon 11 (Met(11) Thr), and in codon 160 (Ala(160) Thr) of the C-terminal domain. CLAD was diagnosed in 88/191 patients, and 60/191 patients have died. Recipients of allografts that expressed the homozygous Met(11) Met variant of aa11 had significantly greater freedom from CLAD development and better survival compared to those with the homozygous Thr(11) Th variant of aa11. No significant association was noted for SP-D variants of aa160. Lung allografts with the SP-D polymorphic variant Thr(11) Th of aa11 are associated with development of CLAD and reduced survival. The observed genetic differences of the donor lung, potentially with their effects on innate immunity, may influence the clinical outcomes after lung transplantation.
慢性肺移植功能障碍(CLAD)是限制肺移植长期成功的主要因素。表面活性剂蛋白 D(SP-D)是肺固有免疫中的一个重要分子,其多态性与各种肺部疾病有关。我们研究了供体肺 SP-D 多态性与 191 例连续接受肺移植的患者移植后 CLAD 和生存的关系。对 191 例接受肺移植的患者进行前瞻性随访,常规进行肺功能检查。通过焦磷酸测序检测供体 DNA,研究 SP-D 两种单核苷酸变异的多态性,这两种单核苷酸变异改变了成熟蛋白 N 端结构域第 11 位(Met(11) Thr)和 C 端结构域第 160 位(Ala(160) Thr)的氨基酸。191 例患者中,88 例诊断为 CLAD,60 例死亡。与携带纯合子 Thr(11) Th 变异的患者相比,表达 aa11 纯合 Met(11) Met 变异的同种异体移植物患者 CLAD 发展的无进展生存率显著更高,生存时间更长。aa160 的 SP-D 变体与无 CLAD 发展或生存时间无关。携带 aa11 的 SP-D 多态性变异 Thr(11) Th 的同种异体肺移植物与 CLAD 的发生和生存时间缩短有关。供体肺的遗传差异可能影响肺移植后的临床结果,而其对固有免疫的影响可能是潜在的原因。