BACKGROUND: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum IgE levels, and eczema. The association of heterozygous signal transducer and activator of transcription 3 (STAT3) mutations with autosomal dominant (AD)-HIES allows the differentiation of AD-HIES from disorders associated with eczema and increased serum IgE levels, such as other primary immunodeficiencies and atopic dermatitis. OBJECTIVE: To facilitate early diagnosis of AD-HIES to initiate appropriate therapy. METHODS: The clinical phenotype (suggested by a National Institutes of Health [NIH] score of >or=40 points), STAT3 genotype, and T(H)17 cell counts were compared in a cohort of 78 patients suspected of having HIES. RESULTS: Heterozygous STAT3 missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score >or=40 points. Patients with STAT3 mutations with HIES showed significantly lower T(H)17 cell counts compared with patients with wild-type STAT3 and control subjects. Only 1 patient with wild-type STAT3 had both an NIH score >or=40 points and abnormal T(H)17 cell counts (<or=0.2% of CD4(+) cells), with this exception being identified with a homozygous dedicator of cytogenesis 8 protein (DOCK8) mutation. Pathologic shedding of primary teeth was present in 3 patients with wild-type STAT3 and 33 patients with STAT3 mutations. Internal abscesses and severe infections were exclusively seen in patients with STAT3 mutations, who also had increased pneumatocele formation and skeletal or connective tissue manifestations compared with patients with wild-type STAT3. CONCLUSION: We expanded the number of STAT3 mutations and validated that the NIH score sensitively identifies patients with HIES. Based on our patient cohort, we propose key findings that, when combined with T(H)17 cell numbers, predict patients with AD-HIES with STAT3 mutations, supporting early diagnosis of AD-HIES. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
BACKGROUND:Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum IgE levels, and eczema. The association of heterozygous signal transducer and activator of transcription 3 (STAT3) mutations with autosomal dominant (AD)-HIES allows the differentiation of AD-HIES from disorders associated with eczema and increased serum IgE levels, such as other primary immunodeficiencies and atopic dermatitis. OBJECTIVE: To facilitate early diagnosis of AD-HIES to initiate appropriate therapy. METHODS: The clinical phenotype (suggested by a National Institutes of Health [NIH] score of >or=40 points), STAT3 genotype, and T(H)17 cell counts were compared in a cohort of 78 patients suspected of having HIES. RESULTS: Heterozygous STAT3 missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score >or=40 points. Patients with STAT3 mutations with HIES showed significantly lower T(H)17 cell counts compared with patients with wild-type STAT3 and control subjects. Only 1 patient with wild-type STAT3 had both an NIH score >or=40 points and abnormal T(H)17 cell counts (<or=0.2% of CD4(+) cells), with this exception being identified with a homozygous dedicator of cytogenesis 8 protein (DOCK8) mutation. Pathologic shedding of primary teeth was present in 3 patients with wild-type STAT3 and 33 patients with STAT3 mutations. Internal abscesses and severe infections were exclusively seen in patients with STAT3 mutations, who also had increased pneumatocele formation and skeletal or connective tissue manifestations compared with patients with wild-type STAT3. CONCLUSION: We expanded the number of STAT3 mutations and validated that the NIH score sensitively identifies patients with HIES. Based on our patient cohort, we propose key findings that, when combined with T(H)17 cell numbers, predict patients with AD-HIES with STAT3 mutations, supporting early diagnosis of AD-HIES. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Authors: Helen L Storr; Sumana Chatterjee; Louise A Metherell; Corinne Foley; Ron G Rosenfeld; Philippe F Backeljauw; Andrew Dauber; Martin O Savage; Vivian Hwa Journal: Endocr Rev Date: 2019-04-01 Impact factor: 19.871
Authors: Claire E Bocchini; Karen Nahmod; Panagiotis Katsonis; Sang Kim; Moses M Kasembeli; Alexandra Freeman; Olivier Lichtarge; George Makedonas; David J Tweardy Journal: Blood Date: 2016-10-31 Impact factor: 22.113
Authors: Alexandra F Freeman; Ellen D Renner; Carolyn Henderson; Anne Langenbeck; Kenneth N Olivier; Amy P Hsu; Beate Hagl; Annette Boos; Joie Davis; Beatriz E Marciano; Lisa Boris; Pamela Welch; Julie Sawalle-Belohradsky; Bernd H Belohradsky; King F Kwong; Steven M Holland Journal: J Clin Immunol Date: 2013-04-13 Impact factor: 8.317
Authors: Lena F Schimke; Nikolaus Rieber; Stacey Rylaarsdam; Otávio Cabral-Marques; Nicholas Hubbard; Anne Puel; Laura Kallmann; Stephanie Anover Sombke; Gundula Notheis; Hans-Peter Schwarz; Birgit Kammer; Tomas Hökfelt; Reinald Repp; Capucine Picard; Jean-Laurent Casanova; Bernd H Belohradsky; Michael H Albert; Hans D Ochs; Ellen D Renner; Troy R Torgerson Journal: J Clin Immunol Date: 2013-05-25 Impact factor: 8.317
Authors: Malte A Kluger; Michael Luig; Claudia Wegscheid; Boeren Goerke; Hans-Joachim Paust; Silke R Brix; Isabell Yan; Hans-Willi Mittrücker; Beate Hagl; Ellen D Renner; Gisa Tiegs; Thorsten Wiech; Rolf A K Stahl; Ulf Panzer; Oliver M Steinmetz Journal: J Am Soc Nephrol Date: 2014-02-07 Impact factor: 10.121