Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA.
Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA.
Transplantation. 2018 Jun;102(6):986-993. doi: 10.1097/TP.0000000000002058.
Aspergillus colonization after lung transplant is associated with an increased risk of chronic lung allograft dysfunction (CLAD). We hypothesized that gene expression during Aspergillus colonization could provide clues to CLAD pathogenesis.
We examined transcriptional profiles in 3- or 6-month surveillance bronchoalveolar lavage fluid cell pellets from recipients with Aspergillus fumigatus colonization (n = 12) and without colonization (n = 10). Among the Aspergillus colonized, we also explored profiles in those who developed CLAD (n = 6) or remained CLAD-free (n = 6). Transcription profiles were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression was based on an absolute fold difference of 2.0 or greater and unadjusted P value less than 0.05. We used NIH Database for Annotation, Visualization and Integrated Discovery for functional analyses, with false discovery rates less than 5% considered significant.
Aspergillus colonization was associated with differential expression of 489 probe sets, representing 404 unique genes. "Defense response" genes and genes in the "cytokine-cytokine receptor" Kyoto Encyclopedia of Genes and Genomes pathway were notably enriched in this list. Among Aspergillus colonized patients, CLAD development was associated with differential expression of 69 probe sets, representing 64 unique genes. This list was enriched for genes involved in "immune response" and "response to wounding", among others. Notably, both chitinase 3-like-1 and chitotriosidase were associated with progression to CLAD.
Aspergillus colonization is associated with gene expression profiles related to defense responses including cytokine signaling. Epithelial wounding, as well as the innate immune response to chitin that is present in the fungal cell wall, may be key in the link between Aspergillus colonization and CLAD.
肺移植后曲霉菌定植与慢性移植物功能障碍（CLAD）的风险增加有关。我们假设曲霉菌定植期间的基因表达可以为 CLAD 发病机制提供线索。
我们检查了 3 或 6 个月监测支气管肺泡灌洗液细胞沉淀中曲霉菌定植（n = 12）和未定植（n = 10）受者的转录谱。在曲霉菌定植的受者中，我们还探讨了发生 CLAD（n = 6）或保持 CLAD 无（n = 6）的患者的谱。转录谱使用 HG-U133 Plus 2.0 微阵列（Affymetrix）进行检测。差异基因表达基于 2.0 或更大的绝对倍数差异和未调整的 P 值小于 0.05。我们使用 NIH 数据库进行注释、可视化和综合发现的功能分析，假发现率小于 5%被认为是显著的。
曲霉菌定植与 489 个探针集的差异表达相关，代表 404 个独特的基因。在这个列表中，“防御反应”基因和“细胞因子-细胞因子受体”京都基因和基因组百科全书途径中的基因显著富集。在曲霉菌定植的患者中，CLAD 的发展与 69 个探针集的差异表达相关，代表 64 个独特的基因。这个列表富含参与“免疫反应”和“对创伤的反应”等基因。值得注意的是，几丁质酶 3 样-1 和壳三糖苷酶都与进展为 CLAD 相关。
曲霉菌定植与包括细胞因子信号在内的防御反应相关的基因表达谱相关。上皮创伤以及真菌细胞壁中存在的几丁质的先天免疫反应，可能是曲霉菌定植与 CLAD 之间联系的关键。
