Defects along the TH17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome

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dc.contributor.authorAl Khatib S.
dc.contributor.authorKeles S.
dc.contributor.authorGarcia-Lloret M.
dc.contributor.authorKarakoc-Aydiner E.
dc.contributor.authorReisli I.
dc.contributor.authorArtac H.
dc.contributor.authorCamcioglu Y.
dc.contributor.authorCokugras H.
dc.contributor.authorSomer A.
dc.contributor.authorKutukculer N.
dc.contributor.authorYilmaz M.
dc.contributor.authorIkinciogullari A.
dc.contributor.authorYegin O.
dc.contributor.authorYüksek M.
dc.contributor.authorGenel F.
dc.contributor.authorKucukosmanoglu E.
dc.contributor.authorBaki A.
dc.contributor.authorBahceciler N.N.
dc.contributor.authorRambhatla A.
dc.contributor.authorNickerson D.W.
dc.contributor.authorMcGhee S.
dc.contributor.authorBarlan I.B.
dc.contributor.authorChatila T.
dc.date.accessioned2019-10-27T08:36:19Z
dc.date.available2019-10-27T08:36:19Z
dc.date.issued2009
dc.departmentEge Üniversitesien_US
dc.description.abstractBackground: The hyper IgE syndrome (HIES) is characterized by abscesses, eczema, recurrent infections, skeletal and connective tissue abnormalities, elevated serum IgE, and diminished inflammatory responses. It exists as autosomal-dominant and autosomal-recessive forms that manifest common and distinguishing clinical features. A majority of those with autosomal-dominant HIES have heterozygous mutations in signal transducer and activator of transcription (STAT)-3 and impaired TH17 differentiation. Objective: To elucidate mechanisms underlying different forms of HIES. Methods: A cohort of 25 Turkish children diagnosed with HIES were examined for STAT3 mutations by DNA sequencing. Activation of STAT3 by IL-6 and IL-21 and STAT1 by IFN-? was assessed by intracellular staining with anti-phospho (p)STAT3 and -pSTAT1 antibodies. TH17 and TH1 cell differentiation was assessed by measuring the production of IL-17 and IFN-?, respectively. Results: Six subjects had STAT3 mutations affecting the DNA binding, Src homology 2, and transactivation domains, including 3 novel ones. Mutation-positive but not mutation-negative subjects with HIES exhibited reduced phosphorylation of STAT3 in response to cytokine stimulation, whereas pSTAT1 activation was unaffected. Both patient groups exhibited impaired TH17 responses, but whereas STAT3 mutations abrogated early steps in TH17 differentiation, the defects in patients with HIES with normal STAT3 affected more distal steps. Conclusion: In this cohort of Turkish children with HIES, a majority had normal STAT3, implicating other targets in disease pathogenesis. Impaired TH17 responses were evident irrespective of the STAT3 mutation status, indicating that different genetic forms of HIES share a common functional outcome. © 2009 American Academy of Allergy, Asthma & Immunology.en_US
dc.identifier.doi10.1016/j.jaci.2009.05.004en_US
dc.identifier.endpage3.48E+07en_US
dc.identifier.issn0091-6749
dc.identifier.issue2en_US
dc.identifier.pmid19577286en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage342en_US
dc.identifier.urihttps://doi.org/10.1016/j.jaci.2009.05.004
dc.identifier.urihttps://hdl.handle.net/11454/27373
dc.identifier.volume124en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMosby Inc.en_US
dc.relation.ispartofJournal of Allergy and Clinical Immunologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectHyper IgE syndromeen_US
dc.subjectIL-21en_US
dc.subjectIL-6en_US
dc.subjectROR?ten_US
dc.subjectSTAT3en_US
dc.subjectTH17en_US
dc.titleDefects along the TH17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndromeen_US
dc.typeArticleen_US

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