Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency

Tom Le Voyer; Sonoko Sakata; Miyuki Tsumura; Taushif Khan; Ana Esteve-Sole; Bandar K Al-Saud; Hatice Eke Gungor; Prasad Taur; Valentine Jeanne-Julien; Mette Christiansen; Lisa-Maria Köhler; Gehad Eltayeb ElGhazali; Jérémie Rosain; Shiho Nishimura; Fumiaki Sakura; Matthieu Bouaziz; Carmen Oleaga-Quintas; Alejandro Nieto-Patlán; Àngela Deyà-Martinez; Yasemin Altuner Torun; Anna-Lena Neehus; Manon Roynard; Sefika Elmas Bozdemir; Nawal Al Kaabi; Moza Al Hassani; Irina Mersiyanova; Flore Rozenberg; Carsten Speckmann; Ina Hainmann; Fabian Hauck; Mohammed Hamdan Alzahrani; Sami Hussain Alhajjar; Saleh Al-Muhsen; Theresa Cole; Ramsay Fuleihan; Peter D Arkwright; Raffaele Badolato; Laia Alsina; Laurent Abel; Mukesh Desai; Hamoud Al-Mousa; Anna Shcherbina; Nico Marr; Stéphanie Boisson-Dupuis; Jean-Laurent Casanova; Satoshi Okada; Jacinta Bustamante

doi:10.4049/jimmunol.2001451

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Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency

Journal article

Peer reviewed

Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency

Tom Le Voyer, Sonoko Sakata, Miyuki Tsumura, Taushif Khan, Ana Esteve-Sole, Bandar K Al-Saud, Hatice Eke Gungor, Prasad Taur, Valentine Jeanne-Julien, Mette Christiansen, …

The Journal of immunology (1950), Vol.207(1), pp.133-152

01/07/2021

DOI: https://doi.org/10.4049/jimmunol.2001451

PMID: 34183371

Abstract

Hematopoietic Stem Cell Transplantation

Humans

Lymphohistiocytosis, Hemophagocytic

Mycobacterium bovis

Mycobacterium Infections

STAT1 Transcription Factor - genetics

STAT1 Transcription Factor - metabolism

Autosomal recessive (AR) STAT1 deficiency is a severe inborn error of immunity disrupting cellular responses to type I, II, and III IFNs, and IL-27, and conferring a predisposition to both viral and mycobacterial infections. We report the genetic, immunological, and clinical features of an international cohort of 32 patients from 20 kindreds: 24 patients with complete deficiency, and 8 patients with partial deficiency. Twenty-four patients suffered from mycobacterial disease (bacillus Calmette-Guérin = 13, environmental mycobacteria = 10, or both in 1 patient). Fifty-four severe viral episodes occurred in sixteen patients, mainly caused by viruses. Attenuated live measles, mumps, and rubella and/or varicella zoster virus vaccines triggered severe reactions in the five patients with complete deficiency who were vaccinated. Seven patients developed features of hemophagocytic syndrome. Twenty-one patients died, and death was almost twice as likely in patients with complete STAT1 deficiency than in those with partial STAT1 deficiency. All but one of the eight survivors with AR complete deficiency underwent hematopoietic stem cell transplantation. Overall survival after hematopoietic stem cell transplantation was 64%. A diagnosis of AR STAT1 deficiency should be considered in children with mycobacterial and/or viral infectious diseases. It is important to distinguish between complete and partial forms of AR STAT1 deficiency, as their clinical outcome and management differ significantly.

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Title: Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency
Creators - without role: Tom Le Voyer - Université Paris Cité
Sonoko Sakata - Hiroshima University
Miyuki Tsumura - Hiroshima University
Taushif Khan - Division of Translational Medicine, Sidra Medicine, Doha, Qatar
Ana Esteve-Sole - Universitat de Barcelona
Bandar K Al-Saud - Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Hatice Eke Gungor - Department of Pediatrics, Pediatric Allergy and Immunology Unit, Kayseri Education and Research Hospital, Erkilet, Kayseri, Turkey
Prasad Taur - Bai Jerbai Wadia Hospital for Children
Valentine Jeanne-Julien - Université Paris Cité
Mette Christiansen - Aarhus University Hospital
Lisa-Maria Köhler - Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
Gehad Eltayeb ElGhazali - Sheikh Khalifa Medical City-Union71, Abu Dhabi and Department of Immunology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Jérémie Rosain - Université Paris Cité
Shiho Nishimura - Hiroshima University
Fumiaki Sakura - Hiroshima University
Matthieu Bouaziz - Université Paris Cité
Carmen Oleaga-Quintas - Université Paris Cité
Alejandro Nieto-Patlán - Research and Development in Bioprocess Unit, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico
Àngela Deyà-Martinez - Universitat de Barcelona
Yasemin Altuner Torun - Istinye University
Anna-Lena Neehus - Université Paris Cité
Manon Roynard - Université Paris Cité
Sefika Elmas Bozdemir - Pediatric İnfectious Disease Unit, Department of Pediatrics, Kayseri Education and Research Hospital, Erkilet, Kayseri, Turkey
Nawal Al Kaabi - Sheikh Khalifa Medical City-Union71, Abu Dhabi and Department of Immunology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Moza Al Hassani - Sheikh Khalifa Medical City-Union71, Abu Dhabi and Department of Immunology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
Irina Mersiyanova - Molecular Biology Laboratory, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
Flore Rozenberg - Université Paris Cité
Carsten Speckmann - University of Freiburg
Ina Hainmann - University Hospital Bonn
Fabian Hauck - Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
Mohammed Hamdan Alzahrani - Security Forces Hospital
Sami Hussain Alhajjar - Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Saleh Al-Muhsen - King Saud University
Theresa Cole - Department of Immunology, The Royal Children's Hospital, Melbourne, Australia
Ramsay Fuleihan - Lurie Children's Hospital
Peter D Arkwright - University of Manchester
Raffaele Badolato - University of Brescia
Laia Alsina - Universitat de Barcelona
Laurent Abel - Rockefeller University
Mukesh Desai - Bai Jerbai Wadia Hospital for Children
Hamoud Al-Mousa - Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Anna Shcherbina - Department of Clinical Immunology and Allergy, Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia
Nico Marr - Division of Translational Medicine, Sidra Medicine, Doha, Qatar
Stéphanie Boisson-Dupuis - Rockefeller University
Jean-Laurent Casanova
Satoshi Okada - Hiroshima University
Jacinta Bustamante - Assistance Publique – Hôpitaux de Paris
Publication Details: The Journal of immunology (1950), Vol.207(1), pp.133-152
Grant note: UL1 TR000043 / NCATS NIH HHS R37 AI095983 / NIAID NIH HHS UL1 TR001866 / NCATS NIH HHS Howard Hughes Medical Institute R01 AI095983 / NIAID NIH HHS
Identifiers: 9951204308331
Academic Unit: King Saud University
Language: English
Resource Type: Journal article