KEGG DISEASE: Defects of toll-like receptor signaling

KEGG

DISEASE: Defects of toll-like receptor signaling

Entry

H00096                      Disease

Name

Defects of toll-like receptor signaling

Subgroup

COVID19-related immunodeficiency-74 (IMD74)

Supergrp

Disorders of innate immunity [DS:H02525]
Primary immunodeficiency disease [DS:H01725]

Description

Human interleukin (IL) 1 receptor-associated kinase 4 (IRAK-4) deficiency is a primary immunodeficiency that impairs Toll/IL-1R immunity, except for the Toll-like receptor (TLR) 3- and TLR4-interferon (IFN)-a/b pathways. IRAK-4 is a kinase that plays a crucial role downstream of individual TLR and IL-1R receptors and upstream of TNF receptor-associated factor-6 (TRAF-6). Patients with IRAK-4 deficiency thus fail to produce TNF-alpha, IL-6, and IFN-gamma in response to IL-1beta and IL-18, respectively. Their blood cells also fail to produce IL-1beta, IL-6, IL-8, IL-12, and TNF-alpha upon stimulation with known TLR agonists. Despite the broad impairment at the two subsequent levels of onset (TLR) and propagation (IL-1R) of inflammation, the clinical phenotype of IRAK-4 deficiency is relatively mild. Patients present no developmental defect and a restricted spectrum of infectious diseases, mostly caused by pyogenic encapsulated bacteria, principally, but not exclusively Gram-positive. Recently, other monogenic defects of toll-like receptor signaling that cause severe immunodeficiency have been reported.

Category

Primary immunodeficiency

Brite

Human diseases in ICD-11 classification [BR:br08403]
04 Diseases of the immune system
  Primary immunodeficiencies
   4A00  Primary immunodeficiencies due to disorders of innate immunity
    H00096  Defects of toll-like receptor signaling
Pathway-based classification of diseases [BR:br08402]
Immune system
  nt06517  TLR signaling
   H00096  Defects of toll-like receptor signaling

Pathway

Toll-like receptor signaling pathway

Network

nt06517 TLR signaling

Gene

(IMD67) IRAK4 [HSA:51135] [KO:K04733]
(IMD39) IRF7 [HSA:3665] [KO:K09447]
(IMD74) TLR7 [HSA:51284] [KO:K05404]
(IMD98) TLR8 [HSA:51311] [KO:K10170]

Other DBs

ICD-11:

OMIM:

607676 616345 301051 301078

Reference

Authors

Kumar A, Teuber SS, Gershwin ME.

Title

Current perspectives on primary immunodeficiency diseases.

Journal

Clin Dev Immunol 13:223-59 (2006)
DOI:10.1080/17402520600800705

Reference

Authors

Morra M, Geigenmuller U, Curran J, Rainville IR, Brennan T, Curtis J, Reichert V, Hovhannisyan H, Majzoub J, Miller DT.

Title

Genetic diagnosis of primary immune deficiencies.

Journal

Immunol Allergy Clin North Am 28:387-412, x (2008)
DOI:10.1016/j.iac.2008.01.004

Reference

Authors

Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarstrom L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J.

Title

Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.

Journal

J Allergy Clin Immunol 120:776-94 (2007)
DOI:10.1016/j.jaci.2007.08.053

Reference

PMID:12637671 (IRAK4)

Authors

Picard C, Puel A, Bonnet M, Ku CL, Bustamante J, Yang K, Soudais C, Dupuis S, Feinberg J, Fieschi C, Elbim C, Hitchcock R, Lammas D, Davies G, Al-Ghonaium A, Al-Rayes H, Al-Jumaah S, Al-Hajjar S, Al-Mohsen IZ, Frayha HH, Rucker R, Hawn TR, Aderem A, Tufenkeji H, Haraguchi S, Day NK, Good RA, Gougerot-Pocidalo MA, Ozinsky A, Casanova JL

Title

Pyogenic bacterial infections in humans with IRAK-4 deficiency.

Journal

Science 299:2076-9 (2003)
DOI:10.1126/science.1081902

Reference

PMID:25814066 (IRF7)

Authors

Ciancanelli MJ, Huang SX, Luthra P, Garner H, Itan Y, Volpi S, Lafaille FG, Trouillet C, Schmolke M, Albrecht RA, Israelsson E, Lim HK, Casadio M, Hermesh T, Lorenzo L, Leung LW, Pedergnana V, Boisson B, Okada S, Picard C, Ringuier B, Troussier F, Chaussabel D, Abel L, Pellier I, Notarangelo LD, Garcia-Sastre A, Basler CF, Geissmann F, Zhang SY, Snoeck HW, Casanova JL

Title

Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency.

Journal

Science 348:448-53 (2015)
DOI:10.1126/science.aaa1578

Reference

PMID:32706371 (TLR7)

Authors

van der Made CI, Simons A, Schuurs-Hoeijmakers J, van den Heuvel G, Mantere T, Kersten S, van Deuren RC, Steehouwer M, van Reijmersdal SV, Jaeger M, Hofste T, Astuti G, Corominas Galbany J, van der Schoot V, van der Hoeven H, Hagmolen Of Ten Have W, Klijn E, van den Meer C, Fiddelaers J, de Mast Q, Bleeker-Rovers CP, Joosten LAB, Yntema HG, Gilissen C, Nelen M, van der Meer JWM, Brunner HG, Netea MG, van de Veerdonk FL, Hoischen A

Title

Presence of Genetic Variants Among Young Men With Severe COVID-19.

Journal

JAMA 324:663-673 (2020)
DOI:10.1001/jama.2020.13719

Reference

PMID:34981838 (TLR8)

Authors

Fejtkova M, Sukova M, Hlozkova K, Skvarova Kramarzova K, Rackova M, Jakubec D, Bakardjieva M, Bloomfield M, Klocperk A, Parackova Z, Sediva A, Aluri J, Novakova M, Kalina T, Fronkova E, Hrusak O, Malcova H, Sedlacek P, Liba Z, Kudr M, Stary J, Cooper MA, Svaton M, Kanderova V

Title

TLR8/TLR7 dysregulation due to a novel TLR8 mutation causes severe autoimmune hemolytic anemia and autoinflammation in identical twins.

Journal

Am J Hematol 97:338-351 (2022)
DOI:10.1002/ajh.26452

LinkDB

» Japanese version

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