EULAR study group on 'MHC-I-opathy' : identifying disease-overarching mechanisms across disciplines and borders

Kuiper, Jonas Jan Willem (author), Vidović Valentinčič, Nataša (author), Turkstra, Franktien (author)

The 'MHC-I (major histocompatibility complex class I)-opathy' concept describes a family of inflammatory conditions with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. Classical MHC-I-opathies such as spondyloarthritis, Behçet's disease, psoriasis and birdshot uveitis are widely recognised for their strong association with certain MHC-I alleles and gene variants of the antigen processing aminopeptidases ERAP1 and ERAP2 that implicates altered MHC-I peptide presentation to CD8$^{+}$ T cells in the pathogenesis. Progress in understanding the cause and treatment of these disorders is hampered by patient phenotypic heterogeneity and lack of systematic investigation of the MHC-I pathway. Here, we discuss new insights into the biology of MHC-I-opathies that strongly advocate for disease-overarching and integrated molecular and clinical investigation to decipher underlying disease mechanisms. Because this requires transformative multidisciplinary collaboration, we introduce the EULAR study group on MHC-I-opathies to unite clinical expertise in rheumatology, dermatology and ophthalmology, with fundamental and translational researchers from multiple disciplines such as immunology, genomics and proteomics, alongside patient partners. We prioritise standardisation of disease phenotypes and scientific nomenclature and propose interdisciplinary genetic and translational studies to exploit emerging therapeutic strategies to understand MHC-I-mediated disease mechanisms. These collaborative efforts are required to address outstanding questions in the etiopathogenesis of MHC-I-opathies towards improving patient treatment and prognostication.

• Language: English
• Keywords: psoriatic arthritis, Behçet syndrome, immune system diseases, ankylosing spondylitis
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: Str. 887-896
• Numbering: Vol. 82, iss. 7
• PID: 20.500.12556/RUL-182309
• UDC: 616-002
• ISSN on article: 0003-4967
• DOI: 10.1136/ard-2022-222852
• COBISS.SI-ID: 275985411
• Publication date in RUL: 07.05.2026

Record is a part of a journal

• Title: Annals of the Rheumatic Diseases
• Shortened title: Ann. Rheum. Dis.
• Publisher: British Medical Association
• ISSN: 0003-4967
• COBISS.SI-ID: 24967936

Licences

• License: CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
• Link: http://creativecommons.org/licenses/by-nc/4.0/
• Description: A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.

Secondary language

• Language: Slovenian
• Keywords: psoriatični artritis, Behçetov sindrom, bolezni imunskega sistema, ankilozirajoči spondilitis