TY - JOUR
T1 - Proteins involved in extracellular matrix dynamics are associated with respiratory syncytial virus disease severity
AU - Schuurhof, Annemieke
AU - Bont, Louis
AU - Hodemaekers, Hennie M.
AU - De Klerk, Arja
AU - De Groot, Hanneke
AU - Hofland, Regina W.
AU - Van De Pol, Alma C.
AU - Kimpen, Jan L.L.
AU - Janssen, Riny
PY - 2012/6/1
Y1 - 2012/6/1
N2 - Severity of respiratory syncytial virus (RSV) infection ranges widely. To what extent the local immune response is involved in RSV disease pathogenesis and which markers of this response are critical in determining disease severity is still a matter of debate. The local immune response was studied in nasopharyngeal aspirates (NPAs) during RSV infection. 47 potential markers of disease severity were analysed in a screening cohort of RSV-infected infants with mild disease at home (n=8), hospitalised infants (n=10) and infants requiring mechanical ventilation (n=7). Results were confirmed in a cohort of infants hospitalised for RSV infection (n=200). Finally, genetic validation was studied in a cohort of infants hospitalised for RSV infection (n=465) and healthy controls (n=930). The concentration of TIMP-1 (tissue inhibitor of metalloproteinase) was higher in the NPAs of hospitalised infants compared with the NPAs of infants at home (1,199 versus 568 ng·mL -1; p<0.0001). Similar results were found for matrix metalloproteinase (MMP)-3 (765 versus 370 pg·mL -1; p=0.004). MMP-3 was confirmed as a marker of disease severity in a larger cohort and MMP3 gene polymorphism rs522616 was associated with severe RSV infection (OR 0.82, p<0.05). In conclusion, extracellular matrix proteinases play an important role in the pathogenesis of RSV bronchiolitis. Copyright
AB - Severity of respiratory syncytial virus (RSV) infection ranges widely. To what extent the local immune response is involved in RSV disease pathogenesis and which markers of this response are critical in determining disease severity is still a matter of debate. The local immune response was studied in nasopharyngeal aspirates (NPAs) during RSV infection. 47 potential markers of disease severity were analysed in a screening cohort of RSV-infected infants with mild disease at home (n=8), hospitalised infants (n=10) and infants requiring mechanical ventilation (n=7). Results were confirmed in a cohort of infants hospitalised for RSV infection (n=200). Finally, genetic validation was studied in a cohort of infants hospitalised for RSV infection (n=465) and healthy controls (n=930). The concentration of TIMP-1 (tissue inhibitor of metalloproteinase) was higher in the NPAs of hospitalised infants compared with the NPAs of infants at home (1,199 versus 568 ng·mL -1; p<0.0001). Similar results were found for matrix metalloproteinase (MMP)-3 (765 versus 370 pg·mL -1; p=0.004). MMP-3 was confirmed as a marker of disease severity in a larger cohort and MMP3 gene polymorphism rs522616 was associated with severe RSV infection (OR 0.82, p<0.05). In conclusion, extracellular matrix proteinases play an important role in the pathogenesis of RSV bronchiolitis. Copyright
KW - Bronchiolitis
KW - Genetic polymorphism
KW - Matrix metalloproteinase-3
KW - Tissue inhibitor of metalloproteinases-1
UR - http://www.scopus.com/inward/record.url?scp=84861872235&partnerID=8YFLogxK
U2 - 10.1183/09031936.00012311
DO - 10.1183/09031936.00012311
M3 - Article
C2 - 22267765
AN - SCOPUS:84861872235
SN - 0903-1936
VL - 39
SP - 1475
EP - 1481
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 6
ER -