BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: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. CONCLUSIONS: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.
Authors: S S Weigt; R M Elashoff; C Huang; A Ardehali; A L Gregson; B Kubak; M C Fishbein; R Saggar; M P Keane; R Saggar; J P Lynch; D A Zisman; D J Ross; J A Belperio Journal: Am J Transplant Date: 2009-05-13 Impact factor: 8.086
Authors: A L Gregson; X Wang; P Injean; S S Weigt; M Shino; D Sayah; A DerHovanessian; J P Lynch; D J Ross; R Saggar; A Ardehali; G Li; R Elashoff; J A Belperio Journal: Am J Transplant Date: 2015-02-12 Impact factor: 8.086
Authors: Marco van Eijk; Cindy P A A van Roomen; G Herma Renkema; Anton P Bussink; Laura Andrews; Edward F C Blommaart; Alan Sugar; Arthur J Verhoeven; Rolf G Boot; Johannes M F G Aerts Journal: Int Immunol Date: 2005-10-07 Impact factor: 4.823
Authors: S Samuel Weigt; Ariss DerHovanessian; W Dean Wallace; Joseph P Lynch; John A Belperio Journal: Semin Respir Crit Care Med Date: 2013-07-02 Impact factor: 3.119
Authors: L Zheng; E H Walters; C Ward; N Wang; B Orsida; H Whitford; T J Williams; T Kotsimbos; G I Snell Journal: Thorax Date: 2000-01 Impact factor: 9.139
Authors: Laurie D Snyder; C Ashley Finlen-Copeland; W Jackson Turbyfill; David Howell; Daniel A Willner; Scott M Palmer Journal: Am J Respir Crit Care Med Date: 2010-02-18 Impact factor: 21.405
Authors: Aric L Gregson; Xiaoyan Wang; S Sam Weigt; Vyacheslav Palchevskiy; Joseph P Lynch; David J Ross; Bernard M Kubak; Rajan Saggar; Michael C Fishbein; Abbas Ardehali; Gang Li; Robert Elashoff; John A Belperio Journal: Am J Respir Crit Care Med Date: 2013-01-17 Impact factor: 21.405
Authors: Daniel R Calabrese; Ping Wang; Tiffany Chong; Jonathan Hoover; Jonathan P Singer; Dara Torgerson; Steven R Hays; Jeffrey A Golden; Jasleen Kukreja; Daniel Dugger; Jason D Christie; John R Greenland Journal: JCI Insight Date: 2019-11-14
Authors: Vyacheslav Palchevskiy; Ying Ying Xue; Rita Kern; Stephen S Weigt; Aric L Gregson; Sophie X Song; Michael C Fishbein; Cory M Hogaboam; David M Sayah; Joseph P Lynch; Michael P Keane; David G Brooks; John A Belperio Journal: JCI Insight Date: 2019-05-14
Authors: Jonathan Hoover; Michelle A Mintz; Fred Deiter; Emily Aminian; Joy Chen; Steven R Hays; Jonathan P Singer; Daniel R Calabrese; Jasleen Kukreja; John R Greenland Journal: Transpl Infect Dis Date: 2021-02-18