Human TYK2 Deficiency: Mycobacterial and Viral Infections without Hyper-IgE Syndrome

dc.creatorMoncada Vélez, Marcela
dc.creatorKreins, Alexandra Yema
dc.creatorCiancanelli, Michael
dc.creatorOkada, Satoshi
dc.creatorKong, Xiao-Fei
dc.creatorRamírez Alejo, Noé
dc.creatorSebnem Kilic, Sara
dc.creatorEl Baghdadi, Jamila
dc.creatorNonoyama, Shigeaki
dc.creatorMahdaviani, Seyed Alireza
dc.creatorAilal, Fatima
dc.creatorBousfiha, Aziz
dc.creatorMansouri, Davood
dc.creatorNievas, Elma
dc.creatorMa, Cindy S.
dc.creatorRao, Geetha
dc.creatorBernasconi, Andrea
dc.creatorKuehn, Hye Sun
dc.creatorNiemela, Julie
dc.creatorStoddard, Jennifer
dc.creatorDeveau, Paul
dc.creatorCobat, Aurelie
dc.creatorEl Azbaoui, Safa
dc.creatorSabri, Ayoub
dc.creatorLim, Che Kang
dc.creatorSundin, Mikael
dc.creatorAvery, Danielle T.
dc.creatorHalwani, Rabih
dc.creatorGrant, Audrey V.
dc.creatorBoisson, Bertrand
dc.creatorBogunovic, Dusan
dc.creatorItan, Yuval
dc.creatorMartínez Barricarte, Rubén
dc.creatorMigaud, Melanie
dc.creatorDeswarte, Caroline
dc.creatorAlsina, Laia
dc.creatorKotlarz, Daniel
dc.creatorKlein, Christoph
dc.creatorFleckenstein, Ingrid Muller
dc.creatorFleckenstein, Bernhard
dc.creatorCormier Daire, Valerie
dc.creatorRose John, Stefan
dc.creatorPicard, Capucine
dc.creatorHammarstrom, Lennart
dc.creatorPuel, Anne
dc.creatorAl Muhsen, Saleh
dc.creatorAbel, Laurent
dc.creatorChaussabel, Damien
dc.creatorRosenzweig, Sergio D.
dc.creatorMinegishi, Yoshiyuki
dc.creatorTangye, Stuart G.
dc.creatorBustamante, Jacinta
dc.creatorCasanova, Jean Laurent
dc.creatorBoisson Dupuis, Stéphanie
dc.date2023-05-25T20:13:47Z
dc.date2023-05-25T20:13:47Z
dc.date2015
dc.date.accessioned2024-04-23T17:46:10Z
dc.date.available2024-04-23T17:46:10Z
dc.identifierKreins AY, Ciancanelli MJ, Okada S, Kong XF, Ramírez-Alejo N, Kilic SS, El Baghdadi J, Nonoyama S, Mahdaviani SA, Ailal F, Bousfiha A, Mansouri D, Nievas E, Ma CS, Rao G, Bernasconi A, Sun Kuehn H, Niemela J, Stoddard J, Deveau P, Cobat A, El Azbaoui S, Sabri A, Lim CK, Sundin M, Avery DT, Halwani R, Grant AV, Boisson B, Bogunovic D, Itan Y, Moncada-Velez M, Martinez-Barricarte R, Migaud M, Deswarte C, Alsina L, Kotlarz D, Klein C, Muller-Fleckenstein I, Fleckenstein B, Cormier-Daire V, Rose-John S, Picard C, Hammarstrom L, Puel A, Al-Muhsen S, Abel L, Chaussabel D, Rosenzweig SD, Minegishi Y, Tangye SG, Bustamante J, Casanova JL, Boisson-Dupuis S. Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome. J Exp Med. 2015 Sep 21;212(10):1641-62. doi: 10.1084/jem.20140280.
dc.identifier0022-1007
dc.identifierhttps://hdl.handle.net/10495/35110
dc.identifier10.1084/jem.20140280
dc.identifier1540-9538
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/9229859
dc.descriptionABSTRACT: Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17(+) T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.
dc.descriptionCOL0012426
dc.format22
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherRockefeller University Press
dc.publisherInmunodeficiencias Primarias
dc.publisherNueva York, Estados Unidos
dc.relationJ. Exp. Med.
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by/2.5/co/
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subjectTYK2 Kinase
dc.subjectTYK2 Quinasa
dc.subjectBacterial Infections
dc.subjectInfecciones Bacterianas
dc.subjectJob Syndrome
dc.subjectSíndrome de Job
dc.subjectImmunoglobulin E
dc.subjectInmunoglobulina E
dc.subjectLoss of Function Mutation
dc.subjectMutación con Pérdida de Función
dc.titleHuman TYK2 Deficiency: Mycobacterial and Viral Infections without Hyper-IgE Syndrome
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.typehttp://purl.org/coar/resource_type/c_2df8fbb1
dc.typehttps://purl.org/redcol/resource_type/ART
dc.typeArtículo de investigación


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