{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:10:51Z","timestamp":1790766651972,"version":"4.1.0"},"reference-count":86,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"unspecified","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2023,8,2]]},"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:p>The human lymphocyte antigen B27 (HLA B27) is a member of the HLA class I family of genes in the major histocompatibility complex whose name goes back to its discovery in studies of transplanted tissue compatibility. Its prevalence in the mid-European population is about 8%. The association of HLA B27 alleles with ankylosing spondylitis (AS), a highly heritable disease, which is part of the spectrum of axial spondyloarthritis (axSpA), was discovered 50 years ago. HLA B27 explains less than 30% of the total genetic load. About 60%\u201390% of axSpA patients worldwide carry HLA B27. The prevalence of the disease is linked to the frequency of HLA B27 in the population which implies that there are relevant differences. Among the roughly 200 subtypes known there are two which are not disease associated. The function of HLA class I molecules is to present peptides to the immune system to defend the organism against microbes targeted by CD8+T cells. This is much supported by the role of the endoplasmic reticulum aminopeptidase 1 (ERAP 1) in AS, an enzyme that is responsible for the intracellular trimming of peptides, since polymorphisms of this gene are only associated with HLA-B27+ disease. The arthritogenic peptide hypothesis trying to explain the pathogenesis of AS is based on that very immune function assuming that also self peptides can be presented. HLA-B27 also plays an important role in classification, diagnosis and severitiy of axSpA.<\/jats:p>","DOI":"10.1136\/rmdopen-2023-003102","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T12:43:14Z","timestamp":1693485794000},"page":"e003102","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":75,"title":["Fifty years after the discovery of the association of HLA B27 with ankylosing spondylitis"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9156-5095","authenticated-orcid":false,"given":"Juergen","family":"Braun","sequence":"first","affiliation":[{"name":"Ruhr University Bochum, Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0285-9890","authenticated-orcid":false,"given":"Joachim","family":"Sieper","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Charite Universitatsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"2025090313030606000_9.3.e003102.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(73)91360-3"},{"key":"2025090313030606000_9.3.e003102.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197304052881403"},{"key":"2025090313030606000_9.3.e003102.3","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.rdc.2017.04.006","article-title":"Genetics and the causes of ankylosing spondylitis","volume":"43","author":"Hanson","year":"2017","journal-title":"Rheum Dis Clin North Am"},{"key":"2025090313030606000_9.3.e003102.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(73)91091-X"},{"key":"2025090313030606000_9.3.e003102.5","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/S0140-6736(74)92431-3","article-title":"Letter: acute anterior uveitis and HL-A 27","volume":"1","author":"Brewerton","year":"1974","journal-title":"Lancet"},{"key":"2025090313030606000_9.3.e003102.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.56"},{"key":"2025090313030606000_9.3.e003102.7","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/s11926-022-01090-6","article-title":"T cell repertoire profiling and the mechanism by which HLA-B27 causes ankylosing spondylitis","volume":"24","author":"Garrido-Mesa","year":"2022","journal-title":"Curr Rheumatol Rep"},{"key":"2025090313030606000_9.3.e003102.8","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-010-0126-x"},{"key":"2025090313030606000_9.3.e003102.9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112110"},{"key":"2025090313030606000_9.3.e003102.10","doi-asserted-by":"publisher","DOI":"10.1038\/353321a0"},{"key":"2025090313030606000_9.3.e003102.11","doi-asserted-by":"publisher","DOI":"10.1038\/353326a0"},{"key":"2025090313030606000_9.3.e003102.12","doi-asserted-by":"publisher","DOI":"10.1084\/jem.175.3.809"},{"key":"2025090313030606000_9.3.e003102.13","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/art.39948","article-title":"Polymorphisms in the F pocket of HLA-B27 subtypes strongly affect assembly, chaperone interactions, and heavy-chain misfolding","volume":"69","author":"Guiliano","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"2025090313030606000_9.3.e003102.14","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199808)28:08<2508::AID-IMMU2508>3.0.CO;2-1"},{"key":"2025090313030606000_9.3.e003102.15","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209512"},{"key":"2025090313030606000_9.3.e003102.16","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21049"},{"key":"2025090313030606000_9.3.e003102.17","first-page":"89","article-title":"Progression of HIV to AIDS: a protective role for HLA B27","volume":"6","author":"den Uyl","year":"2004","journal-title":"AIDS Rev"},{"key":"2025090313030606000_9.3.e003102.18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36587"},{"key":"2025090313030606000_9.3.e003102.19","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1055\/s-0031-1272531","article-title":"Protektiver Effekt von HLA-B27 auf den Verlauf der HIV- und hepatitis-C-virus-Infektion [Protective role of HLA-B27 in HIV and hepatitis C virus infection]","volume":"136","author":"Neumann-Haefelin","year":"2011","journal-title":"Dtsch Med Wochenschr"},{"key":"2025090313030606000_9.3.e003102.20","doi-asserted-by":"crossref","unstructured":"Khan MA . An update on the genetic polymorphism of HLA-B*27 with 213 alleles encompassing 160 subtypes (and still counting). Curr Rheumatol Rep 2017;19. doi:10.1007\/s11926-017-0640-1","DOI":"10.1007\/s11926-017-0640-1"},{"key":"2025090313030606000_9.3.e003102.21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1995.tb02436.x"},{"key":"2025090313030606000_9.3.e003102.22","doi-asserted-by":"publisher","DOI":"10.1002\/art.21308"},{"key":"2025090313030606000_9.3.e003102.23","doi-asserted-by":"crossref","DOI":"10.1186\/s12891-017-1639-5","article-title":"HLA B27 antigen in middle Eastern and Arab countries: systematic review of the strength of association with axial spondyloarthritis and methodological gaps","volume":"18","author":"Ziade","year":"2017","journal-title":"BMC Musculoskelet Disord"},{"key":"2025090313030606000_9.3.e003102.24","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep450"},{"key":"2025090313030606000_9.3.e003102.25","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.041103"},{"key":"2025090313030606000_9.3.e003102.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2012.12.003"},{"key":"2025090313030606000_9.3.e003102.27","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60635-7"},{"key":"2025090313030606000_9.3.e003102.28","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.17"},{"key":"2025090313030606000_9.3.e003102.29","doi-asserted-by":"publisher","DOI":"10.1038\/ng.873"},{"key":"2025090313030606000_9.3.e003102.30","doi-asserted-by":"publisher","DOI":"10.1136\/ard.59.11.883"},{"key":"2025090313030606000_9.3.e003102.31","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200106)44:6<1396::AID-ART233>3.0.CO;2-A"},{"key":"2025090313030606000_9.3.e003102.32","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1016\/S0140-6736(99)03219-5","article-title":"Impact of sex on inheritance of ankylosing spondylitis: a cohort study","volume":"354","author":"Calin","year":"1999","journal-title":"The Lancet"},{"key":"2025090313030606000_9.3.e003102.33","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1007\/s10067-017-3767-6","article-title":"Ethnicity and disease severity in ankylosing spondylitis a cross-sectional analysis of three ethnic groups","volume":"36","author":"Jamalyaria","year":"2017","journal-title":"Clin Rheumatol"},{"key":"2025090313030606000_9.3.e003102.34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/cei.13049","article-title":"Is Beh\u00e7et\u2019s disease a 'class 1-Opathy'? The role of HLA-B*51 in the pathogenesis of Beh\u00e7et\u2019s disease","volume":"191","author":"Giza","year":"2018","journal-title":"Clin Exp Immunol"},{"key":"2025090313030606000_9.3.e003102.35","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2017.01475","article-title":"HLA class I or class II and disease association: catch the difference if you can","volume":"8","author":"Fiorillo","year":"2017","journal-title":"Front Immunol"},{"key":"2025090313030606000_9.3.e003102.36","doi-asserted-by":"publisher","DOI":"10.1038\/ng.513"},{"key":"2025090313030606000_9.3.e003102.37","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms8146","article-title":"Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1","volume":"6","author":"Cortes","year":"2015","journal-title":"Nat Commun"},{"key":"2025090313030606000_9.3.e003102.38","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)91760-J"},{"key":"2025090313030606000_9.3.e003102.39","doi-asserted-by":"publisher","DOI":"10.1002\/art.20948"},{"key":"2025090313030606000_9.3.e003102.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05501-7"},{"key":"2025090313030606000_9.3.e003102.41","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90512-D"},{"key":"2025090313030606000_9.3.e003102.42","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.6.2359"},{"key":"2025090313030606000_9.3.e003102.43","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197510232931701"},{"key":"2025090313030606000_9.3.e003102.44","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199801)41:1<58::AID-ART8>3.0.CO;2-G"},{"key":"2025090313030606000_9.3.e003102.45","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1977.03270510035017"},{"key":"2025090313030606000_9.3.e003102.46","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1976.03260500037025"},{"key":"2025090313030606000_9.3.e003102.47","doi-asserted-by":"publisher","DOI":"10.1007\/s003930050149"},{"key":"2025090313030606000_9.3.e003102.48","doi-asserted-by":"crossref","first-page":"208","DOI":"10.7326\/0003-4819-92-2-208","article-title":"HLA-B27: to type of not to type?","volume":"92","author":"Calin","year":"1980","journal-title":"Ann Intern Med"},{"key":"2025090313030606000_9.3.e003102.49","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-96-1-70"},{"key":"2025090313030606000_9.3.e003102.50","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780270301"},{"key":"2025090313030606000_9.3.e003102.51","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780280107"},{"key":"2025090313030606000_9.3.e003102.52","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204055"},{"key":"2025090313030606000_9.3.e003102.53","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2022-002208","article-title":"Recurrence of axial spondyloarthritis among first-degree relatives in a prospective 35-year-follow-up family study","volume":"8","author":"van der Linden","year":"2022","journal-title":"RMD Open"},{"key":"2025090313030606000_9.3.e003102.54","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780270401"},{"key":"2025090313030606000_9.3.e003102.55","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780341003"},{"key":"2025090313030606000_9.3.e003102.56","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-197409000-00002"},{"key":"2025090313030606000_9.3.e003102.57","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(82)90177-2"},{"key":"2025090313030606000_9.3.e003102.58","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/j.1399-0039.1983.tb00188.x","article-title":"Complete heart block - another HLA B27 associated disease manifestation","volume":"21","author":"Bergfeldt","year":"1983","journal-title":"Tissue Antigens"},{"key":"2025090313030606000_9.3.e003102.59","first-page":"S41","article-title":"Clinical manifestations in HLA-B27-positive patients","volume":"5 Suppl 1","author":"Joos","year":"1987","journal-title":"Clin Exp Rheumatol"},{"key":"2025090313030606000_9.3.e003102.60","doi-asserted-by":"publisher","DOI":"10.1136\/ard.42.6.640"},{"key":"2025090313030606000_9.3.e003102.61","doi-asserted-by":"publisher","DOI":"10.1007\/BF02203394"},{"key":"2025090313030606000_9.3.e003102.62","doi-asserted-by":"publisher","DOI":"10.1016\/0049-0172(90)90023-9"},{"key":"2025090313030606000_9.3.e003102.63","first-page":"249","article-title":"Evaluation of early diagnostic criteria including HLA-B27 for ankylosing spondylitis in a follow-up study","volume":"44","author":"Zeidler","year":"1985","journal-title":"Z Rheumatol"},{"key":"2025090313030606000_9.3.e003102.64","first-page":"82","article-title":"Evaluation of early diagnostic criteria for ankylosing spondylitis in a 10 year follow-up","volume":"49","author":"Mau","year":"1990","journal-title":"Z Rheumatol"},{"key":"2025090313030606000_9.3.e003102.65","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780370709"},{"key":"2025090313030606000_9.3.e003102.66","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08215-6"},{"key":"2025090313030606000_9.3.e003102.67","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.011247"},{"key":"2025090313030606000_9.3.e003102.68","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.108233"},{"key":"2025090313030606000_9.3.e003102.69","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.133645"},{"key":"2025090313030606000_9.3.e003102.70","doi-asserted-by":"publisher","DOI":"10.1136\/ard.47.5.431"},{"key":"2025090313030606000_9.3.e003102.71","doi-asserted-by":"publisher","DOI":"10.1002\/art.24408"},{"key":"2025090313030606000_9.3.e003102.72","doi-asserted-by":"publisher","DOI":"10.1002\/art.24024"},{"key":"2025090313030606000_9.3.e003102.73","doi-asserted-by":"publisher","DOI":"10.1002\/art.24483"},{"key":"2025090313030606000_9.3.e003102.74","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2011.152975"},{"key":"2025090313030606000_9.3.e003102.75","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200025"},{"key":"2025090313030606000_9.3.e003102.76","doi-asserted-by":"publisher","DOI":"10.1002\/art.38050"},{"key":"2025090313030606000_9.3.e003102.77","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1002\/acr.24174","article-title":"The phenotype of axial Spondyloarthritis: is it dependent on HLA-B27 status?","volume":"73","author":"Coates","year":"2021","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2025090313030606000_9.3.e003102.78","doi-asserted-by":"crossref","first-page":"105367","DOI":"10.1016\/j.jbspin.2022.105367","article-title":"Presence of spondyloarthritis associated to higher disease activity and HLA-B27 positivity in patients with early Crohn's disease: clinical and MRI results from a prospective inception cohort","volume":"89","author":"Rios Rodriguez","year":"2022","journal-title":"Joint Bone Spine"},{"key":"2025090313030606000_9.3.e003102.79","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket115"},{"key":"2025090313030606000_9.3.e003102.80","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218669"},{"key":"2025090313030606000_9.3.e003102.81","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-021-02712-7","article-title":"Striking sex differences in magnetic resonance imaging findings in the sacroiliac joints in the population","volume":"24","author":"Braun","year":"2022","journal-title":"Arthritis Res Ther"},{"key":"2025090313030606000_9.3.e003102.82","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-219446"},{"key":"2025090313030606000_9.3.e003102.83","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab314"},{"key":"2025090313030606000_9.3.e003102.84","unstructured":"Khan MA . Spondyloarthropathies. In: Hunder G , ed. Atlas of rheumatology. Philadelphia: Current Medicine, 2005: 151\u201380."},{"key":"2025090313030606000_9.3.e003102.85","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(91)90567-P"},{"key":"2025090313030606000_9.3.e003102.86","doi-asserted-by":"publisher","DOI":"10.1038\/329506a0"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2023-003102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T20:03:18Z","timestamp":1756929798000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2023-003102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":86,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,8,31]]},"published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1136\/rmdopen-2023-003102"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2023-003102","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8]]}}}