Metatranscriptomic Evaluation of Pulmonary Complications after Pediatric Hematopoietic Cell Transplantation Reveals Pathogenic Microbes Linked to Dysregulated Human Immunologic Gene Expression

Abstract

Introduction Pulmonary complications (PCs) after pediatric hematopoietic cell transplant (HCT) are heterogeneous in nature and are strongly associated with transplant-related mortality. Microbial pathogens play a role in the evolution of many post-HCT PCs and may contribute to or develop in the setting of an altered inflammatory microenvironment in the lungs. Objectives To improve characterization of the pulmonary microbiome and transcriptome in pediatric HCT patients with PCs. Methods Bronchoalveolar lavage (BAL) was performed at the University Medical Center in Utrecht between April 2004 and November 2016 for all children Results Relative to pre-HCT patients, post-HCT patients were more likely to have abnormal quantities of RNA aligning to pathogenic microbes (59.6% vs. 40.5%, p=0.017), including RNA aligning to pathogenic bacteria (23.4% vs. 11.0%, p=0.023) and pathogenic viruses (48.9% vs 29.0%, p=0.009), but not pathogenic fungi (6.4% vs 7.1%, p=0.854). In addition, post-HCT patients were also more likely to have depressed bacterial diversity (23.4% vs. 10.0%, p=0.012) and to harbor non-pathogenic viruses (27.7% vs. 7.1%, p Conclusions As detection of pathogenic pulmonary microbes is exceedingly common pre-HCT and increases after HCT, incorporation of host gene expression profiles along with standard diagnostic criteria for pulmonary complications may improve classification accuracy and facilitate patient-targeted therapies. Further investigation into the microbiologic and human transcriptional heterogeneity within these high-risk patients is required.