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Primary immune regulatory disorders: Undiagnosed needles in the haystack?

Lookup NU author(s): Dr Aisling Flinn, Professor Andrew GenneryORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022. The Author(s). Primary Immune Regulatory Disorders (PIRD) describe a group of conditions characterized by loss of normal inflammatory control and immune tolerance mechanisms, with autoimmunity as a predominant clinical feature. PIRD can arise due to defects in the number or function of regulatory T-lymphocytes, defects in the immune mechanisms required to 'turn off' inflammation such as in perforin-dependent cytotoxicity or alterations in cytokine signalling pathways. Diagnosis of PIRD is a significant challenge to physicians due to their rarity, complexity, and diversity in clinical manifestations. Many of these individual conditions lack a genotype-phenotype correlation and display incomplete penetrance. However, establishing a diagnosis is integral in optimizing patient management, including the use of individualized treatment approaches. Increasing awareness among physicians is necessary as patients are likely to present to different subspecialties. Due to the rarity of these conditions, worldwide collaboration and data-sharing is essential to improve our knowledge of the clinical spectrum and disease course in PIRD, and to optimize therapeutic strategies including identification of which patients can benefit from hematopoietic stem cell transplant.

Publication metadata

Author(s): Flinn AM, Gennery AR

Publication type: Review

Publication status: Published

Journal: Orphanet Journal of Rare Diseases

Year: 2022

Volume: 17

Issue: 1

Online publication date: 03/03/2022

Acceptance date: 13/02/2022

ISSN (electronic): 1750-1172

Publisher: BioMed Central Ltd


DOI: 10.1186/s13023-022-02249-1

PubMed id: 35241125