1234. Blood Whole Genome Expression Profiles in Congenital Cytomegalovirus Infection (cCMVi): Is the Asymptomatic Infant Truly Asymptomatic?
Session: Poster Abstract Session: Viral Infections: Pathogenesis and Immunity
Friday, October 9, 2015
Room: Poster Hall
Posters
  • Slide1.jpg (148.1 kB)
  • Background: cCMVi is the most common congenitally acquired infection worldwide and varies from clinically apparent (“symptomatic”) to clinically inapparent (“asymptomatic”) disease. It also  represents the most frequent non-genetic cause of sensorineural hearing loss (SNHL). To date, no biomarker has been identified that can objectively assess disease severity or predict SNHL. Analysis of host genome expression profiles has provided new insights into disease pathogenesis and assessment of clinical severity. Its value as a biomarker in infants with cCMVi has not been explored.

    Methods: 71 infants with cCMVi (39 symptomatic and 32 asymptomatic) and 5 healthy controls (HC) were enrolled at Children’s Medical Center Dallas and Parkland Hospital (Dallas, TX) from 2/2006 to 5/2012. Whole blood samples were collected at a median age of 17 days (range 5-61 days) and RNA transcriptional profiles were compared among groups. Symptomatic cCMVi was defined as the presence of any clinical, laboratory or neuroimaging abnormalities. Infants were followed for development of SNHL.

    Results: Statistical group comparisons between HC and 20 symptomatic cCMV infants identified 1,202 differentially expressed genes (CMV biosignature) that were validated in an independent group of 19 symptomatic cCMV infants with 100% accuracy. The biosignature of symptomatic cCMVi was characterized by overexpression of interferon, T- and B-cell genes, and underexpression of monocyte and inflammation genes. Similar immune profiles were observed in infants with asymptomatic cCMVi. A genomic score applied to the whole cohort showed a significant increase in both cCMVi groups versus HC with no significant differences between infants with symptomatic and asymptomatic cCMVi. Among 15 infants with asymptomatic cCMVi who had audiologic follow-up for at least 3 years, those who developed late-onset SNHL (n=8) showed significant overexpression of T-cell genes when compared with asymptomatic infants without late-onset SNHL (n=7).

    Conclusion: A distinct biosignature was present in infants with cCMVi regardless of their clinical classification (asymptomatic vs. symptomatic). Asymptomatic cCMVi infants who developed SNHL demonstrated overexpression of T-cell genes at diagnosis, suggesting the potential value of immune profiles as predictive biomarkers.

    Christopher Ouellette, MD1, Pablo J. Sanchez, MD, FIDSA, FPIDS1, Bennett Smith, BS2, Fiker Zeray, RN, PNP3, Lizette Torres, RN4, Andrea Ronchi, MD5, Joseph Cantey, MD4, Octavio Ramilo, MD, FPIDS1,2 and Asuncion Mejias, MD, PhD1,2, (1)Pediatrics, Division of Infectious Diseases, Nationwide Children's Hospital, Columbus, OH, (2)Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, (3)Children's Medical Center, Dallas, TX, (4)Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, (5)Clinical Sciences and Community Health, Neonatal Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy

    Disclosures:

    C. Ouellette, None

    P. J. Sanchez, AbbVie Inc: Consultant and Scientific Advisor , Consulting fee and Speaker honorarium
    MedImmune: Grant Investigator , Research support

    B. Smith, None

    F. Zeray, None

    L. Torres, None

    A. Ronchi, None

    J. Cantey, None

    O. Ramilo, None

    A. Mejias, None

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.