Identifying host microRNAs in bronchoalveolar lavage samples from lung transplant recipients infected with Aspergillus

JOURNAL OF HEART AND LUNG TRANSPLANTATION

卷:39

Article

Gohir, Wajiha¹  Klement, William²  Singer, Lianne G.²  Palmer, Scott M.^3,4  Mazzulli, Tony⁵  Keshavjee, Shaf²  Husain, Shahid¹ 

[1] Univ Toronto, Ajmera Family Transplant Ctr, Transplant Infect Dis, Toronto, ON, Canada

[2] Univ Toronto, Univ Hlth Network, Toronto Lung Transplant Program, Toronto, ON, Canada

[3] Duke Univ, Div Pulm & Crit Care Med, Durham, NC USA

[4] Duke Univ, Duke Clin Res Inst, Durham, NC USA

[5] Mt Sinai Hosp, Dept Microbiol, Toronto, ON, Canada

关键词: lung transplantation;    aspergillus;    miRNA;    CLAD;    diagnostic biomarker;   

DOI  :  10.1016/j.healun.2020.07.014

来源: Elsevier

【 摘 要 】

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs of similar to 22 nucleotides that play a crucial role in post-transcriptional regulation of gene expression. Dysregulation of miRNA expression has been shown during microbial infections. We sought to identify miRNAs that distinguish invasive aspergillosis (IA) from non-IA in lung transplant recipients (LTRs). METHODS: We used NanoString nCounter Human miRNA, version 3, panel to measure miRNAs in bronchoalveolar lavage (BAL) samples from LTRs with Aspergillus colonization (ASP group) (n = 10), those with Aspergillus colonization and chronic lung allograft dysfunction (CLAD) (ASPCLAD group) (n = 7), those with IA without CLAD (IA group) (n = 10), those who developed IA with CLAD (IACLAD group) (n = 9), and control patients (controls) (n = 9). The miRNA profile was compared using the permutation test of 100,000 trials for each of the comparisons. We used mirDIP to obtain their gene targets and pathDIP to determine the pathway enrichment. RESULTS: We performed pairwise comparisons between patient groups to identify differentially expressed miRNAs. A total of 5 miRNAs were found to be specific to IA, including 4 (miR-145-5p, miR-424-5p, miR-99b-5p, and miR-4488) that were upregulated and the pair (miR-4454 + miR-7975) that was downregulated in IA group vs controls. The expression change for these miRNAs was specific to patients with IA; they were not significantly differentiated between IACLAD and IA groups. Signaling pathways associated with an immunologic response to IA were found to be significantly enriched. CONCLUSIONS: We report a set of 5 differentially expressed miRNAs in the BAL of LTRs with IA that might help in the development of diagnostic and prognostic tools for IA in LTRs. However, further investigation is needed in a larger cohort to validate the findings. (C) 2020 International Society for Heart and Lung Transplantation. All rights reserved.

【 授权许可】

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