TY - JOUR
T1 - Gene expression profiles in febrile children with defined viral and bacterial infection
AU - Hu, Xinran
AU - Yu, Jinsheng
AU - Crosby, Seth D.
AU - Storch, Gregory A.
PY - 2013/7/30
Y1 - 2013/7/30
N2 - Viral infections are common causes of fever without an apparent source in young children. Despite absence of bacterial infection, many febrile children are treated with antibiotics. Virus and bacteria interact with different pattern recognition receptors in circulating blood leukocytes, triggering specific host transcriptional programs mediating immune response. Therefore, unique transcriptional signatures may be defined that discriminate viral from bacterial causes of fever without an apparent source. Gene expression microarray analyses were conducted on blood samples from 30 febrile children positive for adenovirus, human herpesvirus 6, or enterovirus infection or with acute bacterial infection and 22 afebrile controls. Blood leukocyte transcriptional profiles clearly distinguished virus-positive febrile children from both virus-negative afebrile controls and afebrile children with the same viruses present in the febrile children. Virus-specific gene expression profiles could be defined. The IFN signaling pathway was uniquely activated in febrile children with viral infection, whereas the integrin signaling pathway was uniquely activated in children with bacterial infection. Transcriptional profiles classified febrile children with viral or bacterial infection with better accuracy than white blood cell count in the blood. Similarly accurate classification was shown with data from an independent study using different microarray platforms. Our results support the paradigm of using host response to define the etiology of childhood infections. This approach could be an important supplement to highly sensitive tests that detect the presence of a possible pathogen but do not address its pathogenic role in the patient being evaluated.
AB - Viral infections are common causes of fever without an apparent source in young children. Despite absence of bacterial infection, many febrile children are treated with antibiotics. Virus and bacteria interact with different pattern recognition receptors in circulating blood leukocytes, triggering specific host transcriptional programs mediating immune response. Therefore, unique transcriptional signatures may be defined that discriminate viral from bacterial causes of fever without an apparent source. Gene expression microarray analyses were conducted on blood samples from 30 febrile children positive for adenovirus, human herpesvirus 6, or enterovirus infection or with acute bacterial infection and 22 afebrile controls. Blood leukocyte transcriptional profiles clearly distinguished virus-positive febrile children from both virus-negative afebrile controls and afebrile children with the same viruses present in the febrile children. Virus-specific gene expression profiles could be defined. The IFN signaling pathway was uniquely activated in febrile children with viral infection, whereas the integrin signaling pathway was uniquely activated in children with bacterial infection. Transcriptional profiles classified febrile children with viral or bacterial infection with better accuracy than white blood cell count in the blood. Similarly accurate classification was shown with data from an independent study using different microarray platforms. Our results support the paradigm of using host response to define the etiology of childhood infections. This approach could be an important supplement to highly sensitive tests that detect the presence of a possible pathogen but do not address its pathogenic role in the patient being evaluated.
UR - http://www.scopus.com/inward/record.url?scp=84881086889&partnerID=8YFLogxK
U2 - 10.1073/pnas.1302968110
DO - 10.1073/pnas.1302968110
M3 - Article
C2 - 23858444
AN - SCOPUS:84881086889
SN - 0027-8424
VL - 110
SP - 12792
EP - 12797
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 31
ER -