a Record control number 000268860400023

a ISSN 0091-6749

a Original cataloging agency NEU GrandLibrary

a Language code of text/sound track or separate title eng

a Classification number WD300

b Item number .D44 2009

a Personal name Al Khatib, Shadi.

h Medium Electronic Document

a Title Defects along the T(H)17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome.

c Statement of responsibility, etc Shadi Al Khatib, MD, Sevgi Keles, MD, Maria Garcia-Lloret, MD, Elif Karakoc-Aydiner, MD, Ismail Reisli, MD, Hasibe Artac, MD, Yildiz Camcioglu, MD, Haluk Cokugras, MD,Ayper Somer, MD, Necil Kutukculer, MD, Mustafa Yilmaz, MD,g Aydan Ikinciogullari, MD, Olcay Yegin, MD, Mutlu Yuksek, MD, Ferah Genel, MD, Ercan Kucukosmanoglu, MD,l Ali Baki, MD, Nerin N. Bahceciler, MD, Anupama Rambhatla, Derek W. Nickerson, BS, Sean McGhee, MD, Isil B. Barlan, MD, and Talal Chatila, MD.

b Name of publisher, distributor, etc Mosby-Elsevier,

c Date of publication, distribution, etc 2009.

a Place of publication, distribution, etc New York :

a Summary, etc Background: 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 T(H)17 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-alpha was assessed by intracellular staining with anti-phospho (p)STAT3 and -pSTAT1 antibodies. T(H)17 and T(H)1 cell differentiation was assessed by measuring the production of IL-17 and IFN-gamma, 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. (J Allergy Clin Immunol 2009;124:342-8.)

a Topical term or geographic name as entry element Near East University Article

a Topical term or geographic name as entry element Yakın Doğu Üniversitesi Makale

a Topical term or geographic name as entry element Immunology

a Topical term or geographic name as entry element Allergy

a Topical term or geographic name as entry element Hyper IgE syndrome

g Relationship information AUG 2009,Vol 124 Issue 2, p342-348

t Title Journal Of Allergy And Clinical Immunology

x International Standard Serial Number 00916749

u Uniform Resource Identifier http://library.neu.edu.tr:2048/login?url=http://dx.doi.org/10.1016/j.jaci.2009.05.004