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: 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:
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Authors | Horst von Bernuth, Cheng-Lung Ku, Carlos Rodriguez-Gallego, Shenying Zhang, Ben-Zion Garty, László Maródi, Helen Chapel, Maya Chrabieh, Richard L Miller, Capucine Picard, Anne Puel, Jean-Laurent Casanova |
Journal | Pediatrics
(Pediatrics)
Vol. 118
Issue 6
Pg. 2498-503
(Dec 2006)
ISSN: 1098-4275 [Electronic] United States |
PMID | 17142536
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Membrane Transport Proteins
- Toll-Like Receptors
- UNC93B1 protein, human
- IRAK4 protein, human
- Interleukin-1 Receptor-Associated Kinases
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Topics |
- Child
- Flow Cytometry
- Humans
- Interleukin-1 Receptor-Associated Kinases
(deficiency)
- Membrane Transport Proteins
(deficiency)
- Signal Transduction
- Time Factors
- Toll-Like Receptors
(genetics)
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