International multidisciplinary consensus on the definition and clinical approach for monogenic inflammatory immune dysregulation disorders

Abstract Objective To achieve consensus on the definition and clinical approach of Monogenic Inflammatory Immune Dysregulation Disorders (MIIDDs), a collective term for rare conditions marked by inflammation, immune dysregulation, and infection susceptibility. These consensus guidelines specifically...

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Main Authors: Hend M. Alkwai, Ibrahim A. Almaghlouth, Leonardo Oliveira Mendonça, Shuayb Elkhalifa, Hassan Abolhassani, Suliman Aljumaah, Hamoud Al-Mousa, Mohammed F. Alosaimi, Alhanouf AlSaleem, Tadej Avcin, Winnie KY Chan, Graciela Espada, Marie-Louise Frémond, Ahmet Gül, Djohra Hadef, Nasim Movahedi, Helmut Wittkowski, Sulaiman M. Al-Mayouf
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Pediatric Rheumatology Online Journal
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Online Access:https://doi.org/10.1186/s12969-025-01109-z
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author Hend M. Alkwai
Ibrahim A. Almaghlouth
Leonardo Oliveira Mendonça
Shuayb Elkhalifa
Hassan Abolhassani
Suliman Aljumaah
Hamoud Al-Mousa
Mohammed F. Alosaimi
Alhanouf AlSaleem
Tadej Avcin
Winnie KY Chan
Graciela Espada
Marie-Louise Frémond
Ahmet Gül
Djohra Hadef
Nasim Movahedi
Helmut Wittkowski
Sulaiman M. Al-Mayouf
author_facet Hend M. Alkwai
Ibrahim A. Almaghlouth
Leonardo Oliveira Mendonça
Shuayb Elkhalifa
Hassan Abolhassani
Suliman Aljumaah
Hamoud Al-Mousa
Mohammed F. Alosaimi
Alhanouf AlSaleem
Tadej Avcin
Winnie KY Chan
Graciela Espada
Marie-Louise Frémond
Ahmet Gül
Djohra Hadef
Nasim Movahedi
Helmut Wittkowski
Sulaiman M. Al-Mayouf
author_sort Hend M. Alkwai
collection DOAJ
description Abstract Objective To achieve consensus on the definition and clinical approach of Monogenic Inflammatory Immune Dysregulation Disorders (MIIDDs), a collective term for rare conditions marked by inflammation, immune dysregulation, and infection susceptibility. These consensus guidelines specifically apply to pathogenic (or likely pathogenic) gene mutations affecting both innate and adaptive immunity, excluding variants of unknown significance (VUS). Methods A multi-step, evidence-based, multidisciplinary consensus process was employed, consisting of: (1) a systematic literature review across four electronic databases (Cochrane Library, Web of Science, Scopus, and MEDLINE via PubMed), updated through December 31, 2024; (2) a pre-Delphi electronic survey completed by 95 international adult and pediatric immunologists and rheumatologists; and (3) a modified online Delphi process with an international multidisciplinary expert panel, where statements were iteratively analyzed and refined until achieving consensus (≥ 80% agreement among panelists). Results Fifteen experts from 12 countries participated in two rounds of the Delphi process, resulting in the development of eight overarching principles and 10 consensus statements. These were categorized into five domains: (1) definitions and conceptual framework, (2) diagnostic and monitoring considerations, (3) treatment and therapeutic strategies, (4) multidisciplinary and collaborative care, and (5) patient education and support. Conclusion This consensus defines MIIDDs and provides a structured clinical framework to streamline research efforts and improve patient outcomes.
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spelling doaj-art-f6d1fcff30c145a891d65e2370c260f22025-08-20T03:10:16ZengBMCPediatric Rheumatology Online Journal1546-00962025-05-012311710.1186/s12969-025-01109-zInternational multidisciplinary consensus on the definition and clinical approach for monogenic inflammatory immune dysregulation disordersHend M. Alkwai0Ibrahim A. Almaghlouth1Leonardo Oliveira Mendonça2Shuayb Elkhalifa3Hassan Abolhassani4Suliman Aljumaah5Hamoud Al-Mousa6Mohammed F. Alosaimi7Alhanouf AlSaleem8Tadej Avcin9Winnie KY Chan10Graciela Espada11Marie-Louise Frémond12Ahmet Gül13Djohra Hadef14Nasim Movahedi15Helmut Wittkowski16Sulaiman M. Al-Mayouf17Department of Pediatrics, College of Medicine, University of Ha’ilDepartment of Medicine, College of Medicine, King Saud UniversityDivision of Clinical Immunology and Allergy, Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloAllergy and Immunology Division, Cleveland Clinic Abu DhabiDivision of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska InstitutetDepartment of Pediatric Infectious Diseases, King Faisal Specialist Hospital & Research CentreCollege of Medicine, Alfaisal UniversityImmunology Research Lab, Pediatric Department, College of Medicine, King Saud UniversityDepartment of Pediatric Rheumatology, King Faisal Specialist Hospital and Research CenterUniversity Children’s Hospital, University Medical Centre LjubljanaDepartment of Paediatrics, Queen Elizabeth HospitalHospital de Niños Dr Ricardo GutiérrezPaediatric Haematology-Immunology and Rheumatology Unit, Reference Centre for Inflammatory Rheumatism, Autoimmune Diseases and Systemic Interferonopathies in Children (RAISE), APHP. Centre - Université Paris Cité, Necker HospitalIstanbul Faculty of Medicine, Istanbul UniversityDepartment of Paediatrics, University Hospital Center of BatnaGolestan Rheumatology Research Center (GRRC), Golestan University of Medical SciencesDepartment of Pediatric Rheumatology and Immunology, University Hospital MünsterCollege of Medicine, Alfaisal UniversityAbstract Objective To achieve consensus on the definition and clinical approach of Monogenic Inflammatory Immune Dysregulation Disorders (MIIDDs), a collective term for rare conditions marked by inflammation, immune dysregulation, and infection susceptibility. These consensus guidelines specifically apply to pathogenic (or likely pathogenic) gene mutations affecting both innate and adaptive immunity, excluding variants of unknown significance (VUS). Methods A multi-step, evidence-based, multidisciplinary consensus process was employed, consisting of: (1) a systematic literature review across four electronic databases (Cochrane Library, Web of Science, Scopus, and MEDLINE via PubMed), updated through December 31, 2024; (2) a pre-Delphi electronic survey completed by 95 international adult and pediatric immunologists and rheumatologists; and (3) a modified online Delphi process with an international multidisciplinary expert panel, where statements were iteratively analyzed and refined until achieving consensus (≥ 80% agreement among panelists). Results Fifteen experts from 12 countries participated in two rounds of the Delphi process, resulting in the development of eight overarching principles and 10 consensus statements. These were categorized into five domains: (1) definitions and conceptual framework, (2) diagnostic and monitoring considerations, (3) treatment and therapeutic strategies, (4) multidisciplinary and collaborative care, and (5) patient education and support. Conclusion This consensus defines MIIDDs and provides a structured clinical framework to streamline research efforts and improve patient outcomes.https://doi.org/10.1186/s12969-025-01109-zInborn errors of immunityGeneticInflammatoryAutoimmuneAutoinflammatoryImmune dysregulation
spellingShingle Hend M. Alkwai
Ibrahim A. Almaghlouth
Leonardo Oliveira Mendonça
Shuayb Elkhalifa
Hassan Abolhassani
Suliman Aljumaah
Hamoud Al-Mousa
Mohammed F. Alosaimi
Alhanouf AlSaleem
Tadej Avcin
Winnie KY Chan
Graciela Espada
Marie-Louise Frémond
Ahmet Gül
Djohra Hadef
Nasim Movahedi
Helmut Wittkowski
Sulaiman M. Al-Mayouf
International multidisciplinary consensus on the definition and clinical approach for monogenic inflammatory immune dysregulation disorders
Pediatric Rheumatology Online Journal
Inborn errors of immunity
Genetic
Inflammatory
Autoimmune
Autoinflammatory
Immune dysregulation
title International multidisciplinary consensus on the definition and clinical approach for monogenic inflammatory immune dysregulation disorders
title_full International multidisciplinary consensus on the definition and clinical approach for monogenic inflammatory immune dysregulation disorders
title_fullStr International multidisciplinary consensus on the definition and clinical approach for monogenic inflammatory immune dysregulation disorders
title_full_unstemmed International multidisciplinary consensus on the definition and clinical approach for monogenic inflammatory immune dysregulation disorders
title_short International multidisciplinary consensus on the definition and clinical approach for monogenic inflammatory immune dysregulation disorders
title_sort international multidisciplinary consensus on the definition and clinical approach for monogenic inflammatory immune dysregulation disorders
topic Inborn errors of immunity
Genetic
Inflammatory
Autoimmune
Autoinflammatory
Immune dysregulation
url https://doi.org/10.1186/s12969-025-01109-z
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