The Journal of experimental medicine · 2023

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease.

СтатьяПоддержка исследования: вне правительства СШАResearch Support, N.I.H., IntramuralНазвание и аннотация: Перевод в очереди

Обработка статьи · этапы, ошибки и управление

Загрузка состояния…

История · было → стало

Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.

Sharma Mehul, Leung Daniel, Momenilandi Mana, Jones Lauren C W, Pacillo Lucia, James Alyssa E, Murrell Jill R, Delafontaine Selket, Maimaris Jesmeen, Vaseghi-Shanjani Maryam, Del Bel Kate L, Lu Henry Y, Chua Gilbert T, Di Cesare Silvia, Fornes Oriol, Liu Zhongyi, Di Matteo Gigliola, Fu Maggie P, Amodio Donato, Tam Issan Yee San, Chan Gavin Shueng Wai, Sharma Ashish A, Dalmann Joshua, van der Lee Robin, Blanchard-Rohner Géraldine, Lin Susan, Philippot Quentin, Richmond Phillip A, Lee Jessica J, Matthews Allison, Seear Michael, Turvey Alexandra K, Philips Rachael L, Brown-Whitehorn Terri F, Gray Christopher J, Izumi Kosuke, Treat James R, Wood Kathleen H, Lack Justin, Khleborodova Asya, Niemela Julie E, Yang Xingtian, Liang Rui, Kui Lin, Wong Christina Sze Man, Poon Grace Wing Kit, Hoischen Alexander, van der Made Caspar I, Yang Jing, Chan Koon Wing, Rosa Duque Jaime Sou Da, Lee Pamela Pui Wah, Ho Marco Hok Kung, Chung Brian Hon Yin, Le Huong Thi Minh, Yang Wanling, Rohani Pejman, Fouladvand Ali, Rokni-Zadeh Hassan, Changi-Ashtiani Majid, Miryounesi Mohammad, Puel Anne, Shahrooei Mohammad, Finocchi Andrea, Rossi Paolo, Rivalta Beatrice, Cifaldi Cristina, Novelli Antonio, Passarelli Chiara, Arasi Stefania, Bullens Dominique, Sauer Kate, Claeys Tania, Biggs Catherine M, Morris Emma C, Rosenzweig Sergio D, O'Shea John J, Wasserman Wyeth W, Bedford H Melanie, van Karnebeek Clara D M, Palma Paolo, Burns Siobhan O, Meyts Isabelle, Casanova Jean-Laurent, Lyons Jonathan J, Parvaneh Nima, Nguyen Anh Thi Van, Cancrini Caterina, Heimall Jennifer, Ahmed Hanan, McKinnon Margaret L, Lau Yu Lung, Béziat Vivien, Turvey Stuart E

Аннотация

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

Предметные рубрики MeSH

Humans STAT6 Transcription Factor Gain of Function Mutation Asthma Food Hypersensitivity Immunoglobulin E

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease.

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH