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. 2025 May 14;23(1):51.
doi: 10.1186/s12969-025-01109-z.

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

Hend M Alkwai  1 , Ibrahim A Almaghlouth  2 , Leonardo Oliveira Mendonça  3   4   5 , Shuayb Elkhalifa  6   7 , Hassan Abolhassani  8   9 , Suliman Aljumaah  10   11 , Hamoud Al-Mousa  11   12 , Mohammed F Alosaimi  13 , Alhanouf AlSaleem  14 , Tadej Avcin  15   16 , Winnie Ky Chan  17 , Graciela Espada  18 , Marie-Louise Frémond  19   20 , Ahmet Gül  21 , Djohra Hadef  22   23 , Nasim Movahedi  24   25 , Helmut Wittkowski  26 , Sulaiman M Al-Mayouf  27   28
Affiliations

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

Hend M Alkwai et al. Pediatr Rheumatol Online J. .

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.

Keywords: Autoimmune; Autoinflammatory; Consensus; Genetic; Immune dysregulation; Inborn errors of immunity; Inflammatory.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The research protocol was approved by the Research Advisory Council (RAC) at King Faisal Specialist Hospital and Research Center (RAC2231314). The study was carried out in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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