A fast procedure for the detection of defects in toll-like receptor signaling

Horst Von Bernuth, Cheng Lung Ku, Carlos Rodriguez-Gallego, Shenying Zhang, Ben Zion Garty, L. Máródi, Helen Chapel, Maya Chrabieha, Richard L. Miller, Capucine Picard, Anne Puel, Jean Laurent Casanova

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2498-2503
Number of pages6
JournalPediatrics
Volume118
Issue number6
DOIs
Publication statusPublished - Dec 2006

Fingerprint

Toll-Like Receptors
Interleukin-1 Receptor-Associated Kinases
L-Selectin
Granulocytes
Herpes Simplex Encephalitis
Toll-Like Receptor 8
Flow Cytometry
Toll-Like Receptor 1
Toll-Like Receptor 7
Toll-Like Receptor 2
Inborn Genetic Diseases
Membranes
Simplexvirus
Infection

Keywords

  • Innate immunity
  • Interleukin 1 receptor-associated kinase-4 deficiency
  • L-selectin
  • Primary immunodeficiency
  • Toll-like receptors
  • UNC-93B deficiency

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Von Bernuth, H., Ku, C. L., Rodriguez-Gallego, C., Zhang, S., Garty, B. Z., Máródi, L., ... Casanova, J. L. (2006). A fast procedure for the detection of defects in toll-like receptor signaling. Pediatrics, 118(6), 2498-2503. https://doi.org/10.1542/peds.2006-1845

A fast procedure for the detection of defects in toll-like receptor signaling. / Von Bernuth, Horst; Ku, Cheng Lung; Rodriguez-Gallego, Carlos; Zhang, Shenying; Garty, Ben Zion; Máródi, L.; Chapel, Helen; Chrabieha, Maya; Miller, Richard L.; Picard, Capucine; Puel, Anne; Casanova, Jean Laurent.

In: Pediatrics, Vol. 118, No. 6, 12.2006, p. 2498-2503.

Research output: Contribution to journalArticle

Von Bernuth, H, Ku, CL, Rodriguez-Gallego, C, Zhang, S, Garty, BZ, Máródi, L, Chapel, H, Chrabieha, M, Miller, RL, Picard, C, Puel, A & Casanova, JL 2006, 'A fast procedure for the detection of defects in toll-like receptor signaling', Pediatrics, vol. 118, no. 6, pp. 2498-2503. https://doi.org/10.1542/peds.2006-1845
Von Bernuth H, Ku CL, Rodriguez-Gallego C, Zhang S, Garty BZ, Máródi L et al. A fast procedure for the detection of defects in toll-like receptor signaling. Pediatrics. 2006 Dec;118(6):2498-2503. https://doi.org/10.1542/peds.2006-1845
Von Bernuth, Horst ; Ku, Cheng Lung ; Rodriguez-Gallego, Carlos ; Zhang, Shenying ; Garty, Ben Zion ; Máródi, L. ; Chapel, Helen ; Chrabieha, Maya ; Miller, Richard L. ; Picard, Capucine ; Puel, Anne ; Casanova, Jean Laurent. / A fast procedure for the detection of defects in toll-like receptor signaling. In: Pediatrics. 2006 ; Vol. 118, No. 6. pp. 2498-2503.
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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.",
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AU - Ku, Cheng Lung

AU - Rodriguez-Gallego, Carlos

AU - Zhang, Shenying

AU - Garty, Ben Zion

AU - Máródi, L.

AU - Chapel, Helen

AU - Chrabieha, Maya

AU - Miller, Richard L.

AU - Picard, Capucine

AU - Puel, Anne

AU - Casanova, Jean Laurent

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N2 - 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.

AB - 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.

KW - Innate immunity

KW - Interleukin 1 receptor-associated kinase-4 deficiency

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KW - Primary immunodeficiency

KW - Toll-like receptors

KW - UNC-93B deficiency

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