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International Multidisciplinary Consensus on the Definition and Clinical Approach for Monogenic Inflammatory Immune Dysregulation Disorders Publisher Pubmed



Alkwai HM1 ; Almaghlouth IA2 ; Mendonca LO3, 4, 5 ; Elkhalifa S6, 7 ; Abolhassani H8, 9 ; Aljumaah S10, 11 ; Almousa H11, 12 ; Alosaimi MF13 ; Alsaleem A14 ; Avcin T15, 16 ; Chan WKY17 ; Espada G18 ; Fremond ML19, 20 ; Gul A21 Show All Authors
Authors
  1. Alkwai HM1
  2. Almaghlouth IA2
  3. Mendonca LO3, 4, 5
  4. Elkhalifa S6, 7
  5. Abolhassani H8, 9
  6. Aljumaah S10, 11
  7. Almousa H11, 12
  8. Alosaimi MF13
  9. Alsaleem A14
  10. Avcin T15, 16
  11. Chan WKY17
  12. Espada G18
  13. Fremond ML19, 20
  14. Gul A21
  15. Hadef D22, 23
  16. Movahedi N24, 25
  17. Wittkowski H26
  18. Almayouf SM11, 14
Show Affiliations
Authors Affiliations
  1. 1. Department of Pediatrics, College of Medicine, University of Ha’il, Ha’il, Saudi Arabia
  2. 2. Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  3. 3. Division of Clinical Immunology and Allergy, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil
  4. 4. Discipline of Clinical Immunology, Allergy and Rheumatology, Faculdade de Medicina da Universidade de Santo Amaro, (UNSIA), Sao Paulo, Brazil
  5. 5. Center for Rare and Immunological Diseases, DASA-Hospital 9 de Julho, Sao Paulo, Brazil
  6. 6. Allergy and Immunology Division, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
  7. 7. Faculty of Biology, Medicine and Health, Centre for Musculoskeletal Research, The University of Manchester, Manchester, United Kingdom
  8. 8. Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
  9. 9. Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Department of Pediatric Infectious Diseases, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
  11. 11. College of Medicine, Alfaisal University, Po Box 3354, Riyadh, 11211, Saudi Arabia
  12. 12. Department of Pediatric Allergy and Immunology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  13. 13. Immunology Research Lab, Pediatric Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  14. 14. Department of Pediatric Rheumatology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  15. 15. University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
  16. 16. Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
  17. 17. Department of Paediatrics, Queen Elizabeth Hospital, Kowloon, Hong Kong
  18. 18. Hospital de Ninos Dr Ricardo Gutierrez, Buenos Aires, Argentina
  19. 19. Paediatric Haematology-Immunology and Rheumatology Unit, Reference Centre for Inflammatory Rheumatism, Autoimmune Diseases and Systemic Interferonopathies in Children (RAISE), APHP. Centre - Universite Paris Cite, Necker Hospital, Paris, F-75015, France
  20. 20. Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, INSERM UMR1163, Paris, France
  21. 21. Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
  22. 22. Department of Paediatrics, University Hospital Center of Batna, Batna, Algeria
  23. 23. Faculty of Medicine, Batna 2 University, Batna, Algeria
  24. 24. Golestan Rheumatology Research Center (GRRC), Golestan University of Medical Sciences, Gorgan, Iran
  25. 25. School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
  26. 26. Department of Pediatric Rheumatology and Immunology, University Hospital Munster, Munster, Germany

Source: Pediatric Rheumatology Published:2025


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. © The Author(s) 2025.
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