Imperial College London
Portrait Picture

ProfessorMichaelLevin

Faculty of Medicine, Department of Infectious Disease

Chair in Paediatrics & International Child Health
 
 
 
//

Contact

 

+44 (0)20 7594 3760m.levin Website

 
 
//

Location

 

233Medical SchoolSt Mary's Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Israel:2017:10.1016/j.cell.2017.01.039,
author = {Israel, L and Wang, Y and Bulek, K and Della, Mina E and Zhang, Z and Pedergnana, V and Chrabieh, M and Lemmens, NA and Sancho-Shimizu, V and Descatoire, M and Lasseau, T and Israelsson, E and Lorenzo, L and Yun, L and Belkadi, A and Moran, A and Weisman, LE and Vandenesch, F and Batteux, F and Weller, S and Levin, M and Herberg, J and Abhyankar, A and Prando, C and Itan, Y and van, Wamel WJB and Picard, C and Abel, L and Chaussabel, D and Li, X and Beutler, B and Arkwright, PD and Casanova, J-L and Puel, A},
doi = {10.1016/j.cell.2017.01.039},
journal = {CELL},
pages = {789--800},
title = {Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity},
url = {http://dx.doi.org/10.1016/j.cell.2017.01.039},
volume = {168},
year = {2017}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The molecular basis of the incomplete penetrance of monogenic disorders is unclear. We describe here eight related individuals with autosomal recessive TIRAP deficiency. Life-threatening staphylococcal disease occurred during childhood in the proband, but not in the other seven homozygotes. Responses to all Toll-like receptor 1/2 (TLR1/2), TLR2/6, and TLR4 agonists were impaired in the fibroblasts and leukocytes of all TIRAP-deficient individuals. However, the whole-blood response to the TLR2/6 agonist staphylococcal lipoteichoic acid (LTA) was abolished only in the index case individual, the only family member lacking LTA-specific antibodies (Abs). This defective response was reversed in the patient, but not in interleukin-1 receptor-associated kinase 4 (IRAK-4)-deficient individuals, by anti-LTA monoclonal antibody (mAb). Anti-LTA mAb also rescued the macrophage response in mice lacking TIRAP, but not TLR2 or MyD88. Thus, acquired anti-LTA Abs rescue TLR2-dependent immunity to staphylococcal LTA in individuals with inherited TIRAP deficiency, accounting for incomplete penetrance. Combined TIRAP and anti-LTA Ab deficiencies underlie staphylococcal disease in this patient.
AU  - Israel,L
AU  - Wang,Y
AU  - Bulek,K
AU  - Della,Mina E
AU  - Zhang,Z
AU  - Pedergnana,V
AU  - Chrabieh,M
AU  - Lemmens,NA
AU  - Sancho-Shimizu,V
AU  - Descatoire,M
AU  - Lasseau,T
AU  - Israelsson,E
AU  - Lorenzo,L
AU  - Yun,L
AU  - Belkadi,A
AU  - Moran,A
AU  - Weisman,LE
AU  - Vandenesch,F
AU  - Batteux,F
AU  - Weller,S
AU  - Levin,M
AU  - Herberg,J
AU  - Abhyankar,A
AU  - Prando,C
AU  - Itan,Y
AU  - van,Wamel WJB
AU  - Picard,C
AU  - Abel,L
AU  - Chaussabel,D
AU  - Li,X
AU  - Beutler,B
AU  - Arkwright,PD
AU  - Casanova,J-L
AU  - Puel,A
DO  - 10.1016/j.cell.2017.01.039
EP  - 800
PY  - 2017///
SN  - 0092-8674
SP  - 789
TI  - Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity
T2  - CELL
UR  - http://dx.doi.org/10.1016/j.cell.2017.01.039
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000396284800009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/45808
VL  - 168
ER  -
Download