1315. Mycoplasma pneumoniae (Mp) Induces a Robust Host Transcriptional Profile that Allows Discrimination from Pyogenic Bacteria (PB) in Children Hospitalized with Community-Acquired Pneumonia (CAP)
Session: Poster Abstract Session: Biomarkers and Correlates of Protection
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Background: Mp is a leading cause of CAP in children, especially in those over 5 years of age. However, in hospitalized patients it can be challenging to differentiate CAP caused by Mp from that caused by PB. The present study was designed to identify the transcriptional profile induced by Mp in children and to examine its value in discriminating CAP caused by Mp from PB.

Methods: From February 1, 2011 to May 31, 2012, RNA samples from peripheral whole blood were collected from children hospitalized with CAP and healthy controls (HC). A comprehensive microbiologic diagnostic evaluation for respiratory viruses, PB, and Mp was performed in all patients.  Samples were analyzed using Illumina chips and GeneSpring software. We used class comparisons (Mann-Whitney p<0.01; Benjamini Multiple Test Correction) and modular gene analysis to identify biosignatures for Mp and PB. We performed class prediction (k-NN algorithm) to identify classifier genes that best discriminate Mp from both HC and PB.

Results: Transcriptional profiles from 40 hospitalized children with CAP (27 Mp and 13 PB) and 18 HC were analyzed. Class comparisons identified 1,078 genes differentially expressed in Mp vs HC [ 37% (397) underexpressed and 63% (681) overexpressed] and 5,495 genes in PB vs HC [59% (3,257) underexpressed and 41% (2,238) overexpressed]. Of these genes, 762 wee shared in both infections, while 316 were specific for Mp, and 4,733 were specific for PB. Modular analysis in children with Mp revealed overexpression of genes related to interferon, inflammation, and neutrophils, and suppression of genes related to lymphoid lineage and B-, T-, and NK-cells. The k-NN algorithm identified 35 classifier genes that best discriminated Mp vs HC with an overall accuracy of 95% and 22 classifier genes that best discriminated Mp vs PB with 88% accuracy.

Conclusion: Children hospitalized with CAP caused by Mp and PB exhibit robust but distinct transcriptional profiles.  Overall the Mp profile is characterized by overexpression of innate immune genes and suppression of adaptive immunity genes. Despite the overlap between the profiles of CAP caused by Mp and PB, the k-NN algorithm identified 22 genes that accurately distinguished between these two types of CAP.

Rebecca Wallihan, MD, Department of Pediatrics, Section of Infectious Diseases, Nationwide Children's Hospital (NCH) and The Ohio State University College of Medicine, Columbus, OH, Nicolas M. Suarez, PhD, Center for Vaccines and Immunity, The Research Institute At Nationwide Children's Hospital, Columbus, OH, Mario Marcon, PhD, Department of Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, Asuncion Mejias, MD, PhD, Center for Vaccines & Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH and Octavio Ramilo, MD, Pediatrics, Nationwide, Columbus, OH

Disclosures:

R. Wallihan, None

N. M. Suarez, None

M. Marcon, None

A. Mejias, None

O. Ramilo, Abbott Molecular: Grant Investigator, Grant recipient
Abbott Labs: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium
Merck: Consultant, Consulting fee
Gilead: Scientific Advisor, Consulting fee
Quidel: Scientific Advisor, Consulting fee
Roche: Consultant, Consulting fee

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