Host miRNA Profile of Invasive Aspergillosis in Lung Transplant Recipients

Abstract

Purpose MicroRNAs (miRNAs) are small noncoding RNAs of ∼22 nucleotides that play a crucial role in post-transcriptional regulation of gene expression. Dysregulation of miRNA expression has been shown during various microbial infections. We sought to identify the miRNAs that distinguish invasive aspergillosis (IA) from non-IA in transplant recipients. Methods We used the Nanostring nCounter Human miRNA v3 panel to measure human miRNAs in bronchoalveolar lavage (BAL) samples collected from lung transplant recipients (LTRs) with IA (n=10) and without IA (n=9). We also measured human miRNA in peripheral blood mononuclear cells (PBMCs) collected from 6 hematological malignancy patients with IA and 6 healthy controls. The miRNA profile was compared using the permutation test of 100000 trials for each of the comparisons. We used mirDip (http://ophid.utoronto.ca/mirDIP/index.jsp#r) to obtain their gene targets. Subsequently we used pathDIP (http://ophid.utoronto.ca/pathDIP/) to determine the corresponding pathway enrichment. Results When we analyzed BAL samples of LTRs (10 IA samples vs 9 non-IA samples), we found that the expression of 58 miRNAs was significantly different (p-value < 0.05) between the two groups. We also found 48 miRNAs that were significant different when comparing 6 IA vs. 6 non-IA PBMC samples. We selected 4 miRNAs that had differential expression in both blood and BAL, and had at least 2 folds change in both blood and BAL for IA for pathway analysis. These included hsa-miR-101-3p, hsa-miR-1285-5p, hsa-miR-99b-5p and hsa-miR-877-5p (Fig 1a and b). These miRNAs target 449 genes, including genes regulating toll-like receptors, IL2, IL-6, IL-7 and IL 17 signaling pathways. Conclusion This preliminary data suggests that IA may have a distinctive miRNA profile that can assist in the diagnosis and prognostication of these patients. Further work is required in a larger cohort to validate these findings. MicroRNAs (miRNAs) are small noncoding RNAs of ∼22 nucleotides that play a crucial role in post-transcriptional regulation of gene expression. Dysregulation of miRNA expression has been shown during various microbial infections. We sought to identify the miRNAs that distinguish invasive aspergillosis (IA) from non-IA in transplant recipients. We used the Nanostring nCounter Human miRNA v3 panel to measure human miRNAs in bronchoalveolar lavage (BAL) samples collected from lung transplant recipients (LTRs) with IA (n=10) and without IA (n=9). We also measured human miRNA in peripheral blood mononuclear cells (PBMCs) collected from 6 hematological malignancy patients with IA and 6 healthy controls. The miRNA profile was compared using the permutation test of 100000 trials for each of the comparisons. We used mirDip (http://ophid.utoronto.ca/mirDIP/index.jsp#r) to obtain their gene targets. Subsequently we used pathDIP (http://ophid.utoronto.ca/pathDIP/) to determine the corresponding pathway enrichment. When we analyzed BAL samples of LTRs (10 IA samples vs 9 non-IA samples), we found that the expression of 58 miRNAs was significantly different (p-value < 0.05) between the two groups. We also found 48 miRNAs that were significant different when comparing 6 IA vs. 6 non-IA PBMC samples. We selected 4 miRNAs that had differential expression in both blood and BAL, and had at least 2 folds change in both blood and BAL for IA for pathway analysis. These included hsa-miR-101-3p, hsa-miR-1285-5p, hsa-miR-99b-5p and hsa-miR-877-5p (Fig 1a and b). These miRNAs target 449 genes, including genes regulating toll-like receptors, IL2, IL-6, IL-7 and IL 17 signaling pathways. This preliminary data suggests that IA may have a distinctive miRNA profile that can assist in the diagnosis and prognostication of these patients. Further work is required in a larger cohort to validate these findings.