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Gohir W, Klement W, Singer LG, et al. Identifying host microRNAs in bronchoalveolar lavage samples from lung transplant recipients infected with Aspergillus. J Heart Lung Transplant. 2020;39(11):1228-1237doi: 10.1016/j.healun.2020.07.014.
Gohir, W., Klement, W., Singer, L. G., Palmer, S. M., Mazzulli, T., Keshavjee, S., & Husain, S. (2020). Identifying host microRNAs in bronchoalveolar lavage samples from lung transplant recipients infected with Aspergillus. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 39(11), 1228-1237. https://doi.org/10.1016/j.healun.2020.07.014
Gohir, Wajiha, et al. "Identifying host microRNAs in bronchoalveolar lavage samples from lung transplant recipients infected with Aspergillus." The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation vol. 39,11 (2020): 1228-1237. doi: https://doi.org/10.1016/j.healun.2020.07.014
Gohir W, Klement W, Singer LG, Palmer SM, Mazzulli T, Keshavjee S, Husain S. Identifying host microRNAs in bronchoalveolar lavage samples from lung transplant recipients infected with Aspergillus. J Heart Lung Transplant. 2020 Nov;39(11):1228-1237. doi: 10.1016/j.healun.2020.07.014. Epub 2020 Jul 25. PMID: 32771440.
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J Heart Lung Transplant. 2020 Nov;39(11):1228-1237. doi: 10.1016/j.healun.2020.07.014. Epub 2020 Jul 25.

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

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

Wajiha Gohir, William Klement, Lianne G Singer, Scott M Palmer, Tony Mazzulli, Shaf Keshavjee, Shahid Husain

Affiliations

  1. Transplant Infectious Diseases, Ajmera Family Transplant Centre.
  2. Toronto Lung Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  3. Division of Pulmonary and Critical Care Medicine, Duke University, Durham, North Carolina; Duke Clinical Research Institute, Duke University, Durham, North Carolina.
  4. Department of Microbiology, Mount Sinai Hospital, Toronto, Ontario, Canada.
  5. Transplant Infectious Diseases, Ajmera Family Transplant Centre. Electronic address: [email protected].

PMID: 32771440 DOI: 10.1016/j.healun.2020.07.014

Abstract

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs of ∼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.

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Keywords: CLAD; aspergillus; diagnostic biomarker; lung transplantation; miRNA

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