Masakatsu Yanagimachi1,2, Takashi Ohya3, Tomoko Yokosuka3, Ryosuke Kajiwara3, Fumiko Tanaka3, Hiroaki Goto3, Takehiro Takashima4, Tomohiro Morio4, Shumpei Yokota3. 1. Department of Pediatrics, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, Japan. m.yanagimachi@gmail.com. 2. Department of Pediatrics, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. m.yanagimachi@gmail.com. 3. Department of Pediatrics, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, Japan. 4. Department of Pediatrics, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
Abstract
PURPOSE: Autosomal dominant hyper-IgE syndrome (AD-HIES) is included among primary immunodeficiencies, and results from heterozygous mutations in the signal transduction and activator of transcription 3 (STAT3) gene. AD-HIES leads to impaired Th17 cell differentiation and IL-17 production, and is associated with increased susceptibility to bacteria and fungi. It was reported that several patients with AD-HIES were treated with hematopoietic stem cell transplantation (HSCT). The efficacy of HSCT in treating AD-HIES is variable. This study aims to evaluate the long-term clinical and immunological efficacy of HSCT for AD-HIES. METHODS: We have followed for more than 8 years two patients with AD-HIES who were treated with HSCT. Their ability of IL-17 production was evaluated by flow cytometry. RESULTS: Both patients indicated the normal ability of IL-17 production and their serum IgE levels decreased after HSCT. On the other hand, they suffered from pulmonary complications of AD-HIES such as pneumatoceles and bronchiectasis even after HSCT; however, the frequency of infections was decreased. CONCLUSIONS: Although the dysfunction of STAT3 in non-hematological tissues such as the lungs could not be corrected by HSCT, AD-HIES patients with risk factors for pulmonary complications may benefit from immunological correction by HSCT before severe pulmonary complications occur. Future studies should investigate risk factors for pulmonary complications in AD-HIES patients.
PURPOSE:Autosomal dominant hyper-IgE syndrome (AD-HIES) is included among primary immunodeficiencies, and results from heterozygous mutations in the signal transduction and activator of transcription 3 (STAT3) gene. AD-HIES leads to impaired Th17 cell differentiation and IL-17 production, and is associated with increased susceptibility to bacteria and fungi. It was reported that several patients with AD-HIES were treated with hematopoietic stem cell transplantation (HSCT). The efficacy of HSCT in treating AD-HIES is variable. This study aims to evaluate the long-term clinical and immunological efficacy of HSCT for AD-HIES. METHODS: We have followed for more than 8 years two patients with AD-HIES who were treated with HSCT. Their ability of IL-17 production was evaluated by flow cytometry. RESULTS: Both patients indicated the normal ability of IL-17 production and their serum IgE levels decreased after HSCT. On the other hand, they suffered from pulmonary complications of AD-HIES such as pneumatoceles and bronchiectasis even after HSCT; however, the frequency of infections was decreased. CONCLUSIONS: Although the dysfunction of STAT3 in non-hematological tissues such as the lungs could not be corrected by HSCT, AD-HIESpatients with risk factors for pulmonary complications may benefit from immunological correction by HSCT before severe pulmonary complications occur. Future studies should investigate risk factors for pulmonary complications in AD-HIESpatients.
Authors: John S Cho; Eric M Pietras; Nairy C Garcia; Romela Irene Ramos; David M Farzam; Holly R Monroe; Julie E Magorien; Andrew Blauvelt; Jay K Kolls; Ambrose L Cheung; Genhong Cheng; Robert L Modlin; Lloyd S Miller Journal: J Clin Invest Date: 2010-04-01 Impact factor: 14.808
Authors: Alexandra F Freeman; David E Kleiner; Hari Nadiminti; Joie Davis; Martha Quezado; Victoria Anderson; Jennifer M Puck; Steven M Holland Journal: J Allergy Clin Immunol Date: 2007-03-01 Impact factor: 10.793
Authors: Natalia I Dmitrieva; Avram D Walts; Dai Phuong Nguyen; Alex Grubb; Xue Zhang; Xujing Wang; Xianfeng Ping; Hui Jin; Zhen Yu; Zu-Xi Yu; Dan Yang; Robin Schwartzbeck; Clifton L Dalgard; Beth A Kozel; Mark D Levin; Russell H Knutsen; Delong Liu; Joshua D Milner; Diego B López; Michael P O'Connell; Chyi-Chia Richard Lee; Ian A Myles; Amy P Hsu; Alexandra F Freeman; Steven M Holland; Guibin Chen; Manfred Boehm Journal: J Clin Invest Date: 2020-08-03 Impact factor: 14.808
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: Yael Gernez; Alexandra F Freeman; Steven M Holland; Elizabeth Garabedian; Niraj C Patel; Jennifer M Puck; Kathleen E Sullivan; Javeed Akhter; Elizabeth Secord; Karin Chen; Rebecca Buckley; Elie Haddad; Hans D Ochs; Ramsay Fuleihan; John Routes; Mica Muskat; Patricia Lugar; Julien Mancini; Charlotte Cunningham-Rundles Journal: J Allergy Clin Immunol Pract Date: 2017-09-19
Authors: Pilar Blanco Lobo; Paloma Guisado-Hernández; Isabel Villaoslada; Beatriz de Felipe; Carmen Carreras; Hector Rodriguez; Begoña Carazo-Gallego; Ana Méndez-Echevarria; José Manuel Lucena; Pilar Ortiz Aljaro; María José Castro; José Francisco Noguera-Uclés; Joshua D Milner; Katelyn McCann; Ofer Zimmerman; Alexandra F Freeman; Michail S Lionakis; Steven M Holland; Olaf Neth; Peter Olbrich Journal: J Clin Immunol Date: 2022-05-04 Impact factor: 8.542
Authors: Ian A Myles; Erik D Anderson; Noah J Earland; Kol A Zarember; Inka Sastalla; Kelli W Williams; Portia Gough; Ian N Moore; Sundar Ganesan; Cedar J Fowler; Arian Laurence; Mary Garofalo; Douglas B Kuhns; Mark D Kieh; Arhum Saleem; Pamela A Welch; Dirk A Darnell; John I Gallin; Alexandra F Freeman; Steven M Holland; Sandip K Datta Journal: J Clin Invest Date: 2018-07-23 Impact factor: 14.808
Authors: Stephanie C Harrison; Christo Tsilifis; Mary A Slatter; Zohreh Nademi; Austen Worth; Paul Veys; Mark J Ponsford; Stephen Jolles; Waleed Al-Herz; Terence Flood; Andrew J Cant; Rainer Doffinger; Gabriela Barcenas-Morales; Ben Carpenter; Rachael Hough; Ásgeir Haraldsson; Jennifer Heimall; Bodo Grimbacher; Mario Abinun; Andrew R Gennery Journal: J Clin Immunol Date: 2021-02-01 Impact factor: 8.317