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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

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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