Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/48637
Title: A fast procedure for the detection of defects in toll-like receptor signaling
Authors: Von Bernuth, Horst
Ku, Cheng Lung
Rodriguez-Gallego, Carlos 
Zhang, Shenying
Garty, Ben Zion
Maródi, László
Chapel, Helen
Chrabieha, Maya
Miller, Richard L.
Picard, Capucine
Puel, Anne
Casanova, Jean Laurent
UNESCO Clasification: 32 Ciencias médicas
320110 Pediatría
Keywords: Flow cytometry
Interleukin-1
Signal transduction
Issue Date: 2006
Journal: Pediatrics 
Abstract: Objectives: Inborn defects in Toll-like receptor signaling are recently described primary immunodeficiencies that predispose affected children to life-threatening infections. Patients with interleukin-1 receptor-associated kinase-4 deficiency are prone to invasive pneumococcal disease, and patients with UNC-93B deficiency are prone to herpes simplex virus encephalitis. These genetic disorders are underdiagnosed, partly because diagnosis currently requires expensive and time-consuming techniques available at only a few specialized centers worldwide. We, therefore, aimed to develop a cheap and fast test for the detection of defects in Toll-like receptor signaling. Patients and methods: We used flow cytometry to evaluate the cleavage of membrane-bound L-selectin on granulocytes in 38 healthy controls and in 7 patients with genetically defined Toll-like receptor signaling defects (5 patients with interleukin-1 receptor-associated kinase-4 deficiency and 2 patients with UNC-93B deficiency), on activation with various Toll-like receptor agonists. Results: Impaired L-selectin shedding was observed with granulocytes from all of the interleukin-1 receptor-associated kinase-4-deficient patients on activation with agonists of Toll-like receptors 1/2, 2/6, 4, 7, and 8 and with granulocytes from all of the UNC-93B-deficient patients on activation with agonists of Toll-like receptors 7 and 8. All of the healthy controls responded to these stimuli. Conclusions: The assessment of membrane-bound L-selectin cleavage on granulocytes by flow cytometry may prove useful for the detection of primary immunodeficiencies in the Toll-like receptor pathway, such as interleukin-1 receptor-associated kinase-4 deficiency and UNC-93B deficiency. This procedure is cheap and rapid. It may, therefore, be suitable for routine testing worldwide in children with invasive pneumococcal disease and in patients with herpes simplex encephalitis.
URI: http://hdl.handle.net/10553/48637
ISSN: 0031-4005
DOI: 10.1542/peds.2006-1845
Source: Pediatrics[ISSN 0031-4005],v. 118, p. 2498-2503
Appears in Collections:Artículos
Show full item record

SCOPUSTM   
Citations

50
checked on Jun 26, 2022

Page view(s)

18
checked on Jun 12, 2022

Google ScholarTM

Check

Altmetric


Share



Export metadata



Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.