European Society for Immunodeficiencies guidelines for the management of patients with congenital athymia

Collaborators, Affiliations

Collaborators

European Society for Immunodeficiencies Clinical Working Party:
Siobhan O Burns¹², Maria Carrabba¹³, Ann Gardulf¹⁴, Filomeen Haerynck¹⁵, Fabian Hauck¹⁶, Peter Jandus¹⁷, Isabelle Meyts¹⁸, Adam Klocperk¹⁹, Bénédicte Neven²⁰, Malgorzata Pac²¹, Martine Pergent²², Anna Sediva¹⁹, Pere Soler-Palacín²³, Margarita Velcheva²⁴, Klaus Warnatz²⁵

Affiliations

¹ Department of Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Infection Immunity and Inflammation Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London, United Kingdom. Electronic address: a.kreins@ucl.ac.uk.
² Department of Paediatrics and Institute of Developmental and Regenerative Medicine, University of Oxford, Oxford, United Kingdom; Department of Clinical Immunology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
³ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Paediatric Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom; Department of Paediatric Immunology, Children's Health Ireland at Crumlin, Crumlin, Ireland.
⁴ Department of Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
⁵ Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶ San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Hospital, Milan, Italy; Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale Delle Ricerche (IRGB-CNR), Milan, Italy.
⁷ Department of Pediatrics, Pediatric Stem Cell Transplantation Program, Willem-Alexander Children's Hospital, Leiden, The Netherlands; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
⁸ Institute of Immunology and Immunotherapy, Medical School, University of Birmingham, Birmingham, United Kingdom.
⁹ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Paediatric Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
¹⁰ Department of Paediatrics and Institute of Developmental and Regenerative Medicine, University of Oxford, Oxford, United Kingdom; Paediatric Immunology, Department of Biomedicine, University of Basel and University Children's Hospital Basel, Basel, Switzerland; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
¹¹ Department of Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Infection Immunity and Inflammation Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.
¹² Institute of Immunity and Transplantation, University College London, and Department of Immunology, The Royal Free London NHS Foundation Trust, London, United Kingdom.
¹³ Internal Medicine Department, RITA-ERN Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.
¹⁴ Division of Clinical Immunology and Transfusion Medicine, The Unit for Clinical Research, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
¹⁵ Primary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Ghent University, and Department of Pediatric Pulmonology, Infectious Diseases and Immune Deficiency, Centre for Primary Immune Deficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium.
¹⁶ Division of Pediatric Immunology and Rheumatology, Department of Pediatrics, Dr von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
¹⁷ Division of Clinical Immunology and Allergy, Department of Medicine, University Hospital and Medical Faculty, University of Geneva, Geneva, Switzerland.
¹⁸ Department of Pediatrics, University Hospital Leuven, and Laboratory for Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven, and FWO Vlaanderen and JMF Diagnostic and Research Center Leuven, Leuven, Belgium.
¹⁹ Department of Immunology, 2nd Faculty of Medicine Charles University, University Hospital in Motol, Prague, Czechia.
²⁰ Pediatric Hematology-Immunology and Rheumatology Department, Assistance Publique Hôpitaux de Paris, Paris, France; Necker University Hospital, and Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR-S-1163, and Université Paris Cité, Paris, France.
²¹ Department of Immunology, The Children's Memorial Health Institute, Warsaw, Poland.
²² The International Patient Organisation for Primary Immunodeficiencies, Brussels, Belgium.
²³ Pediatric Infectious Diseases and Immunodeficiencies Unit, University Hospital Vall d'Hebron, and Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
²⁴ Kenes Group, Amsterdam, Netherlands.
²⁵ Department of Rheumatology and Clinical Immunology and Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

PMID: 39303894
DOI: 10.1016/j.jaci.2024.07.031

Free article

Review

European Society for Immunodeficiencies guidelines for the management of patients with congenital athymia

Alexandra Y Kreins et al. J Allergy Clin Immunol. 2024 Dec.

Free article

. 2024 Dec;154(6):1391-1408.

doi: 10.1016/j.jaci.2024.07.031. Epub 2024 Sep 18.

Collaborators

European Society for Immunodeficiencies Clinical Working Party:
Siobhan O Burns¹², Maria Carrabba¹³, Ann Gardulf¹⁴, Filomeen Haerynck¹⁵, Fabian Hauck¹⁶, Peter Jandus¹⁷, Isabelle Meyts¹⁸, Adam Klocperk¹⁹, Bénédicte Neven²⁰, Malgorzata Pac²¹, Martine Pergent²², Anna Sediva¹⁹, Pere Soler-Palacín²³, Margarita Velcheva²⁴, Klaus Warnatz²⁵

Affiliations

¹ Department of Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Infection Immunity and Inflammation Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London, United Kingdom. Electronic address: a.kreins@ucl.ac.uk.
² Department of Paediatrics and Institute of Developmental and Regenerative Medicine, University of Oxford, Oxford, United Kingdom; Department of Clinical Immunology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
³ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Paediatric Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom; Department of Paediatric Immunology, Children's Health Ireland at Crumlin, Crumlin, Ireland.
⁴ Department of Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
⁵ Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶ San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Hospital, Milan, Italy; Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale Delle Ricerche (IRGB-CNR), Milan, Italy.
⁷ Department of Pediatrics, Pediatric Stem Cell Transplantation Program, Willem-Alexander Children's Hospital, Leiden, The Netherlands; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
⁸ Institute of Immunology and Immunotherapy, Medical School, University of Birmingham, Birmingham, United Kingdom.
⁹ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Paediatric Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
¹⁰ Department of Paediatrics and Institute of Developmental and Regenerative Medicine, University of Oxford, Oxford, United Kingdom; Paediatric Immunology, Department of Biomedicine, University of Basel and University Children's Hospital Basel, Basel, Switzerland; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
¹¹ Department of Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Infection Immunity and Inflammation Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.
¹² Institute of Immunity and Transplantation, University College London, and Department of Immunology, The Royal Free London NHS Foundation Trust, London, United Kingdom.
¹³ Internal Medicine Department, RITA-ERN Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.
¹⁴ Division of Clinical Immunology and Transfusion Medicine, The Unit for Clinical Research, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
¹⁵ Primary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Ghent University, and Department of Pediatric Pulmonology, Infectious Diseases and Immune Deficiency, Centre for Primary Immune Deficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium.
¹⁶ Division of Pediatric Immunology and Rheumatology, Department of Pediatrics, Dr von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
¹⁷ Division of Clinical Immunology and Allergy, Department of Medicine, University Hospital and Medical Faculty, University of Geneva, Geneva, Switzerland.
¹⁸ Department of Pediatrics, University Hospital Leuven, and Laboratory for Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven, and FWO Vlaanderen and JMF Diagnostic and Research Center Leuven, Leuven, Belgium.
¹⁹ Department of Immunology, 2nd Faculty of Medicine Charles University, University Hospital in Motol, Prague, Czechia.
²⁰ Pediatric Hematology-Immunology and Rheumatology Department, Assistance Publique Hôpitaux de Paris, Paris, France; Necker University Hospital, and Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR-S-1163, and Université Paris Cité, Paris, France.
²¹ Department of Immunology, The Children's Memorial Health Institute, Warsaw, Poland.
²² The International Patient Organisation for Primary Immunodeficiencies, Brussels, Belgium.
²³ Pediatric Infectious Diseases and Immunodeficiencies Unit, University Hospital Vall d'Hebron, and Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
²⁴ Kenes Group, Amsterdam, Netherlands.
²⁵ Department of Rheumatology and Clinical Immunology and Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

PMID: 39303894
DOI: 10.1016/j.jaci.2024.07.031

Abstract

Congenital athymia is a life-limiting disorder due to rare inborn errors of immunity causing impaired thymus organogenesis or abnormal thymic stromal cell development and function. Athymic infants have a T-lymphocyte-negative, B-lymphocyte-positive, natural killer cell-positive immunophenotype with profound T-lymphocyte deficiency and are susceptible to severe infections and autoimmunity. Patients variably display syndromic features. Expanding access to newborn screening for severe combined immunodeficiency and T lymphocytopenia and broad genetic testing, including next-generation sequencing technologies, increasingly facilitate their timely identification. The recommended first-line treatment is allogeneic thymus transplantation, which is a specialized procedure available in Europe and the United States. Outcomes for athymic patients are best with early diagnosis and thymus transplantation before the development of infectious and inflammatory complications. These guidelines on behalf of the European Society for Immunodeficiencies provide a comprehensive review for clinicians who manage patients with inborn thymic stromal cell defects; they offer clinical practice recommendations focused on the diagnosis, investigation, risk stratification, and management of congenital athymia with the aim of improving patient outcomes.

Keywords: 22q11.2 deletion syndrome; Congenital athymia; DiGeorge syndrome; immunology guidelines; thymus transplantation.

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Conflict of interest statement

Disclosure statement A.Y.K. is supported by the Wellcome Trust (222096/Z/20/Z). F.D. is supported by an NIHR Academic Clinical Lectureship and an Academy for Medical Sciences Starter Grant. E.H. and E.G.D. are supported by a grant from the Great Ormond Street Hospital Children’s Charity. O.E.’s laboratory is supported by grants from the Swedish Research Council (2018-02752 and 2022-00781) and the Swedish state under an ALF agreement between the Swedish government and the county councils (ALFGBG-965795). A.V. is supported by a core grant from the Telethon Foundation. F.J.T.’s laboratory is supported in part by EU H2020 grant RECOMB (755170–(b)) and has received funding from the European UnionHorizon 2020 research and innovation program as well as from reNEW, the Novo Nordisk Foundation for Stem Cell Research (NNF21CC0073729). G.A. is supported by an MRC Programme Grant to GA (MR/T029765/a). and G.H. is supported by the Wellcome Trust (211944/Z/18/Z). Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

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European Society for Immunodeficiencies guidelines for the management of patients with congenital athymia

Collaborators

Affiliations

European Society for Immunodeficiencies guidelines for the management of patients with congenital athymia

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

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LinkOut - more resources

Full Text Sources