Revisiting MHC Genes in Spondyloarthritis

Overview

Journal Curr Rheumatol Rep

Publisher Current Science

Specialty Rheumatology

Date 2015 Apr 24

PMID 25903667

Citations 8

Authors

Maxime Breban

Felicie Costantino

Claudine Andre

Gilles Chiocchia

Henri-Jean Garchon

Affiliations

Soon will be listed here.

Abstract

Spondyloarthritis (SpA) refers to a variety of inflammatory rheumatic disorders with strong heritability. Shared genetic predisposition, as shown by familial aggregation, is largely attributable to the major histocompatibility complex (MHC) locus, which was estimated to account for approximately half of the whole disease heritability. The first predisposing allele identified more than 40 years ago is HLA-B27, which is a major gene predisposing to all forms of SpA. However, despite intensive research, its pathogenesis remains uncertain. Other MHC alleles belonging to the class I and class II regions have been identified to exert additional effect. Candidate-gene approaches and genome-wide studies have recently allowed identification of several new loci residing outside of the MHC region that are involved in the predisposition to SpA. Interestingly, some of those new genes, such as ERAP1, ERAP2, and NPEPPS, code for aminopeptidases that are involved in MHC class I presentation and were shown to interact with HLA-B27.

Citing Articles

TGFβ signaling pathway is altered by HLA-B27 expression, resulting in pathogenic consequences relevant for spondyloarthritis.

Lauraine M, de Taffin de Tilques M, Melamed-Kadosh D, Cherqaoui B, Rincheval V, Prevost E Arthritis Res Ther. 2024; 26(1):131.

PMID: 39010233 PMC: 11247877. DOI: 10.1186/s13075-024-03370-1.

CD8 T and NK cells characterized by upregulation of NPEPPS and ABHD17A are associated with the co-occurrence of type 2 diabetes and coronary artery disease.

Dai C, Wang D, Tao Q, Li Z, Zhai P, Wang Y Front Immunol. 2024; 15:1267963.

PMID: 38464509 PMC: 10921359. DOI: 10.3389/fimmu.2024.1267963.

Human Leukocyte Antigen B*27-Negative Spondyloarthritis: Clinical, Serological, and Radiological Features of a Single-Center Cohort.

Mariani F, Alunno A, Di Ruscio E, Altieri P, Ferri C, Carubbi F Diagnostics (Basel). 2023; 13(23).

PMID: 38066792 PMC: 10706745. DOI: 10.3390/diagnostics13233550.

Genetics, Epigenetics, and Gender Impact in Axial-Spondyloarthritis Susceptibility: An Update on Genetic Polymorphisms and Their Sex Related Associations.

Chimenti M, Perricone C, DAntonio A, Ferraioli M, Conigliaro P, Triggianese P Front Genet. 2021; 12:671976.

PMID: 34447407 PMC: 8383732. DOI: 10.3389/fgene.2021.671976.

The Association of Fecal Microbiota in Ankylosing Spondylitis Cases with C-Reactive Protein and Erythrocyte Sedimentation Rate.

Liu G, Hao Y, Yang Q, Deng S Mediators Inflamm. 2020; 2020:8884324.

PMID: 33204218 PMC: 7666627. DOI: 10.1155/2020/8884324.

References

Jeanty C, Sourisce A, Noteuil A, Jah N, Wielgosik A, Fert I . HLA-B27 subtype oligomerization and intracellular accumulation patterns correlate with predisposition to spondyloarthritis. Arthritis Rheumatol. 2014; 66(8):2113-23. DOI: 10.1002/art.38644. View

Garcia-Medel N, Sanz-Bravo A, Alvarez-Navarro C, Gomez-Molina P, Barnea E, Marcilla M . Peptide handling by HLA-B27 subtypes influences their biological behavior, association with ankylosing spondylitis and susceptibility to endoplasmic reticulum aminopeptidase 1 (ERAP1). Mol Cell Proteomics. 2014; 13(12):3367-80. PMC: 4256490. DOI: 10.1074/mcp.M114.039214. View

Neerinckx B, Carter S, Lories R . No evidence for a critical role of the unfolded protein response in synovium and blood of patients with ankylosing spondylitis. Ann Rheum Dis. 2013; 73(3):629-30. DOI: 10.1136/annrheumdis-2013-204170. View

Paladini F, Belfiore F, Cocco E, Carcassi C, Cauli A, Vacca A . HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia. Arthritis Res Ther. 2009; 11(6):R171. PMC: 3003531. DOI: 10.1186/ar2860. View

Costantino F, Talpin A, Evnouchidou I, Kadi A, Leboime A, Said-Nahal R . ERAP1 Gene Expression Is Influenced by Nonsynonymous Polymorphisms Associated With Predisposition to Spondyloarthritis. Arthritis Rheumatol. 2015; 67(6):1525-34. DOI: 10.1002/art.39072. View

Ciccia F, Accardo-Palumbo A, Rizzo A, Guggino G, Raimondo S, Giardina A . Evidence that autophagy, but not the unfolded protein response, regulates the expression of IL-23 in the gut of patients with ankylosing spondylitis and subclinical gut inflammation. Ann Rheum Dis. 2013; 73(8):1566-74. PMC: 3883901. DOI: 10.1136/annrheumdis-2012-202925. View

Reveille J, Sims A, Danoy P, Evans D, Leo P, Pointon J . Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet. 2010; 42(2):123-7. PMC: 3224997. DOI: 10.1038/ng.513. View

Miceli-Richard C, Zouali H, Said-Nahal R, Lesage S, Merlin F, De Toma C . Significant linkage to spondyloarthropathy on 9q31-34. Hum Mol Genet. 2004; 13(15):1641-8. DOI: 10.1093/hmg/ddh179. View

Diaz-Pena R, Vidal-Castineira J, Mulero J, Sanchez A, Queiro R, Lopez-Larrea C . Activating killer immunoglobulin-like receptors genes are associated with increased susceptibility to ankylosing spondylitis. Clin Exp Immunol. 2014; 180(2):201-6. PMC: 4408154. DOI: 10.1111/cei.12568. View

10.

Diyarbakir E, Eyerci N, Melikoglu M, Topcu A, Pirim I . HLA B27 subtype distribution among patients with ankylosing spondylitis in eastern Turkey. Genet Test Mol Biomarkers. 2012; 16(5):456-8. DOI: 10.1089/gtmb.2011.0183. View

11.

Wei J, Tsai W, Lin H, Tsai C, Chou C . HLA-B60 and B61 are strongly associated with ankylosing spondylitis in HLA-B27-negative Taiwan Chinese patients. Rheumatology (Oxford). 2004; 43(7):839-42. DOI: 10.1093/rheumatology/keh193. View

12.

Liu X, Hu L, Li Y, Chen F, Ning Y, Yao Q . The association of HLA-B*27 subtypes with ankylosing spondylitis in Wuhan population of China. Rheumatol Int. 2009; 30(5):587-90. DOI: 10.1007/s00296-009-1018-0. View

13.

Rudwaleit M, van der Heijde D, Landewe R, Akkoc N, Brandt J, Chou C . The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis. 2010; 70(1):25-31. DOI: 10.1136/ard.2010.133645. View

14.

Brown M, Laval S, Brophy S, Calin A . Recurrence risk modelling of the genetic susceptibility to ankylosing spondylitis. Ann Rheum Dis. 2000; 59(11):883-6. PMC: 1753017. DOI: 10.1136/ard.59.11.883. View

15.

Diaz-Pena R, Castro-Santos P, Aransay A, Bruges-Armas J, Pimentel-Santos F, Lopez-Larrea C . Genetic study confirms association of HLA-DPA1(∗)01:03 subtype with ankylosing spondylitis in HLA-B27-positive populations. Hum Immunol. 2013; 74(6):764-7. DOI: 10.1016/j.humimm.2013.02.001. View

16.

Diaz-Pena R, Aransay A, Bruges-Armas J, Lopez-Vazquez A, Rodriguez-Ezpeleta N, Mendibil I . Fine mapping of a major histocompatibility complex in ankylosing spondylitis: association of the HLA-DPA1 and HLA-DPB1 regions. Arthritis Rheum. 2011; 63(11):3305-12. DOI: 10.1002/art.30555. View

17.

Fert I, Glatigny S, Poulain C, Satumtira N, Dorris M, Taurog J . Correlation between dendritic cell functional defect and spondylarthritis phenotypes in HLA-B27/HUMAN beta2-microglobulin-transgenic rat lines. Arthritis Rheum. 2008; 58(11):3425-9. DOI: 10.1002/art.24023. View

18.

Talpin A, Costantino F, Bonilla N, Leboime A, Letourneur F, Jacques S . Monocyte-derived dendritic cells from HLA-B27+ axial spondyloarthritis (SpA) patients display altered functional capacity and deregulated gene expression. Arthritis Res Ther. 2014; 16(4):417. PMC: 4292999. DOI: 10.1186/s13075-014-0417-0. View

19.

Breban M, Miceli-Richard C, Zinovieva E, Monnet D, Said-Nahal R . The genetics of spondyloarthropathies. Joint Bone Spine. 2006; 73(4):355-62. DOI: 10.1016/j.jbspin.2005.11.010. View

20.

Hacquard-Bouder C, Chimenti M, Giquel B, Donnadieu E, Fert I, Schmitt A . Alteration of antigen-independent immunologic synapse formation between dendritic cells from HLA-B27-transgenic rats and CD4+ T cells: selective impairment of costimulatory molecule engagement by mature HLA-B27. Arthritis Rheum. 2007; 56(5):1478-89. DOI: 10.1002/art.22572. View