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

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'...

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Bibliographic Details
Published in:	Annals of the rheumatic diseases Vol. 82; no. 7; p. 887
Main Authors:	Kuiper, Jonas Jw, Prinz, Jörg C, Stratikos, Efstratios, Kuśnierczyk, Piotr, Arakawa, Akiko, Springer, Sebastian, Mintoff, Dillon, Padjen, Ivan, Shumnalieva, Russka, Vural, Seçil, Kötter, Ina, van de Sande, Marleen G, Boyvat, Ayşe, de Boer, Joke H, Bertsias, George, de Vries, Niek, Krieckaert, Charlotte Lm, Leal, Inês, Vidovič Valentinčič, Nataša, Tugal-Tutkun, Ilknur, El Khaldi Ahanach, Hanane, Costantino, Félicie, Glatigny, Simon, Mrazovac Zimak, Danijela, Lötscher, Fabian, Kerstens, Floor G, Bakula, Marija, Viera Sousa, Elsa, Böhm, Peter, Bosman, Kees, Kenna, Tony J, Powis, Simon J, Breban, Maxime, Gul, Ahmet, Bowes, John, Lories, Rik Ju, Nowatzky, Johannes, Wolbink, Gerrit Jan, McGonagle, Dennis G, Turkstra, Franktien
Format:	Journal Article
Language:	English
Published:	England 01-07-2023
Subjects:	Aminopeptidases - genetics Behcet Syndrome - genetics Genetic Predisposition to Disease Histocompatibility Antigens Class I - genetics Humans Minor Histocompatibility Antigens - genetics Spondylarthritis Uveitis Behcet Syndrome Immune System Diseases Spondylitis, Ankylosing Arthritis, Psoriatic
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Summary:	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.
ISSN:	1468-2060
DOI:	10.1136/ard-2022-222852