RT Journal Article
SR Electronic
T1 Proteins involved in extracellular matrix dynamics are associated with RSV disease severity
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP erj00123-2011
DO 10.1183/09031936.00012311
A1 A. Schuurhof
A1 L. Bont
A1 H.M. Hodemaekers
A1 A. de Klerk
A1 H. de Groot
A1 R.W. Hofland
A1 A.C. van de Pol
A1 J.L.L. Kimpen
A1 R. Janssen
YR 2012
UL http://erj.ersjournals.com/content/early/2012/01/19/09031936.00012311.abstract
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 matter of debate.The local immune response was studied in nasopharyngeal aspirates (NPAs) during RSV infection. Forty-seven 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).TIMP metallopeptidase inhibitor (TIMP)-1 was higher in the NPAs of hospitalised infants compared to the NPAs of infants at home (1,199 vs 568 ng·mL−1, p<0.0001). Similar results were found for matrix metalloproteinase (MMP)-3 (765 vs 370 pg·mL−1, p=0.004). MMP-3 as a marker of disease severity was confirmed in a larger cohort and MMP3 gene polymorphism rs522616 was associated with severe RSV infection (OR 0.82, p<0.05).Extracellular matrix proteinases play an important role in the pathogenesis of RSV bronchiolitis.