Association between common toll-like receptor 4 mutations and severe respiratory syncytial virus disease

Guy Tal, Avigdor Mandelberg, Ilan Dalal, Karine Cesar, Eli Somekh, Asher Tal, Anat Oron, Svetlana Itskovich, Ami Ballin, Sion Houri, Avraham Beigelman, Ofer Lider, Gideon Rechavi, Ninette Amariglio

Research output: Contribution to journalArticlepeer-review

291 Scopus citations

Abstract

Background. The clinical spectrum of respiratory syncytial virus (RSV) bronchiolitis in previously healthy infants is extremely variable. Thus, it is likely that factors such as genetic heterogeneity contribute to disease severity. Toll-like receptor 4 (TLR4) and CD14 are part of a receptor complex involved in the innate immune response to RSV. Methods. The association of the TLR4 mutations (Asp299Gly and Thr399Ile) and the CD14/-159 polymorphism were analyzed in 99 infants hospitalized with severe RSV bronchiolitis (group I). Eighty-two ambulatory infants with mild RSV bronchiolitis (group II) and 90 healthy adults (group III) composed the 2 control groups. The TLR4 mutations and the CD14/-159 polymorphism were genotyped by use of reverse-transcriptase polymerase chain reaction and restriction fragment-length polymorphism analysis, respectively. Results. Each of the TLR4 mutations, either alone or in cosegregation, were associated with severe RSV bronchiolitis: the Asp299Gly and Thr399Ile mutations were significantly overrepresented in group I, compared with groups II and III. No association between the CD14/-159 polymorphism and RSV bronchiolitis was found. Conclusions. These findings suggest that TLR4 mutations, but not the CD14/-159 polymorphism, are associated with an increased risk of severe RSV bronchiolitis in previously healthy infants.

Original languageEnglish
Pages (from-to)2057-2063
Number of pages7
JournalJournal of Infectious Diseases
Volume189
Issue number11
DOIs
StatePublished - 1 Jun 2004
Externally publishedYes

Bibliographical note

Funding Information:
Received 24 August 2003; accepted 1 December 2003; electronically published 12 May 2004. Financial support: Rebecca and Harry Bernard Fund for Pediatric Research, Tel-Aviv University; Shulamit Svirsky Research Fund, Tel-Aviv University. G.R. holds the Gregorio and Dora Shapiro Chair in Hematologic Malignancies, Tel-Aviv University. a G.T. and A.M. contributed equally to this work. Reprints or correspondence: Dr. Ilan Dalal, Dept. of Pediatrics, E. Wolfson Medical Center, Holon 58100, Israel ([email protected]).

Funding

Received 24 August 2003; accepted 1 December 2003; electronically published 12 May 2004. Financial support: Rebecca and Harry Bernard Fund for Pediatric Research, Tel-Aviv University; Shulamit Svirsky Research Fund, Tel-Aviv University. G.R. holds the Gregorio and Dora Shapiro Chair in Hematologic Malignancies, Tel-Aviv University. a G.T. and A.M. contributed equally to this work. Reprints or correspondence: Dr. Ilan Dalal, Dept. of Pediatrics, E. Wolfson Medical Center, Holon 58100, Israel ([email protected]).

FundersFunder number
Rebecca and Harry Bernard Fund for Pediatric Research
Tel-Aviv University

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