{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:35:19Z","timestamp":1788849319741,"version":"build-2803163510"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100012495","name":"Spondylitis Association of America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012495","id-type":"DOI","asserted-by":"publisher"}]},{"name":"William and Mary Bauman Family Foundation"},{"name":"Grandmaison Fund for Autoimmunity Research"},{"name":"Stan and Madelle Rosenfeld Family Trust"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>HLA-B27 is associated with increased susceptibility and disease activity of ankylosing spondylitis, but the effect of HLA-B27 on the activity of the broader category now called axial spondyloarthritis (AxSpA) is apparently the opposite. A modified Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess disease activity among 3435 patients with spondyloarthritis (SpA) who participated in a survey designed to assess the effect of their disease and its treatment on the susceptibility and severity of Covid-19. Chi square testing was used to compare BASDAI scores between HLA-B27 positive and negative subjects. 2836 survey respondents were HLA B27 positive. The average BASDAI for the HLA-B27 negative cohort was 4.92 compared to 4.34 for the HLA-B27 positive subjects. Based on linear regression, a subject\u2019s sex could not fully account for the differing BASDAI score in HLA-B27 negative subjects compared to those who are HLA-B27 positive. The difference between B27 positive and negative subjects was skewed by those with a BASDAI score of one or two. HLA-B27 positive subjects were more than twice as likely to have a BASDAI score of 1 compared to HLA B27 negative subjects and about 60% more likely to have a BASDAI score of 2 (p\u2009&lt;\u20090.0001). HLA-B27 positive subjects have less active spondyloarthritis compared to HLA-B27 negative subjects as measured by a BASDAI score. Our data indicate that patients with mild back pain and a diagnosis of AxSpA are disproportionately HLA-B27 positive. The HLA-B27 test facilitates the diagnosis of axial spondyloarthritis such that patients from a community survey with mild back pain may be disproportionately diagnosed as having AxSpA if they are HLA-B27 positive. The test result likely introduces a cognitive bias into medical decision making and could explain our observations.<\/jats:p>","DOI":"10.1038\/s41598-021-91829-5","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T10:02:58Z","timestamp":1623319378000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["HLA-B27 is associated with reduced disease activity in axial spondyloarthritis"],"prefix":"10.1038","volume":"11","author":[{"given":"James T.","family":"Rosenbaum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Weisman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedley","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassie","family":"Shafer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elin","family":"Aslanyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Howard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Ogle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Reveille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin L.","family":"Winthrop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongseok","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"issue":"7809","key":"91829_CR1","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1016\/S0140-6736(73)91360-3","volume":"1","author":"DA Brewerton","year":"1973","unstructured":"Brewerton, D. A. et al. Ankylosing spondylitis and HL-A 27. Lancet 1(7809), 904\u2013907 (1973).","journal-title":"Lancet"},{"issue":"14","key":"91829_CR2","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1056\/NEJM197304052881403","volume":"288","author":"L Schlosstein","year":"1973","unstructured":"Schlosstein, L., Terasaki, P. I., Bluestone, R. & Pearson, C. M. High association of an HL-A antigen, W27, with ankylosing spondylitis. N. Engl. J. Med. 288(14), 704\u2013706 (1973).","journal-title":"N. Engl. J. Med."},{"key":"91829_CR3","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1136\/ard.50.3.154","volume":"50","author":"TL Reynolds","year":"1991","unstructured":"Reynolds, T. L., Khan, M. A., Van Der Linden, S. & Cleveland, P. Differences in HLA-B27 positive and negative patients with ankylosing spondylitis: Study of clinical disease activity and concentrations of serum IgA, C reactive protein, and haptoglobin. Ann. Rheum. Dis. 50, 154\u2013157 (1991).","journal-title":"Ann. Rheum. Dis."},{"issue":"4","key":"91829_CR4","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1002\/art.1780200401","volume":"20","author":"MA Khan","year":"1977","unstructured":"Khan, M. A., Kushner, I. & Braun, W. E. Comparison of clinical features in HLA-B27 positive and negative patients with ankylosing spondylitis. Arthritis Rheum. 20(4), 909\u2013912 (1977).","journal-title":"Arthritis Rheum."},{"issue":"4","key":"91829_CR5","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1097\/00002281-200207000-00004","volume":"14","author":"MA Brown","year":"2002","unstructured":"Brown, M. A., Crane, A. M. & Wordsworth, B. P. Genetic aspects of susceptibility, severity, and clinical expression in ankylosing spondylitis. Curr. Opin. Rheumatol. 14(4), 354\u2013360 (2002).","journal-title":"Curr. Opin. Rheumatol."},{"issue":"supplement","key":"91829_CR6","doi-asserted-by":"publisher","first-page":"111","DOI":"10.3109\/03009749009097070","volume":"87","author":"A Linssen","year":"1990","unstructured":"Linssen, A. B27+ disease versus B27\u2212 disease. Scand. J. Rheumatol. 87(supplement), 111\u2013118 (1990).","journal-title":"Scand. J. Rheumatol."},{"issue":"2","key":"91829_CR7","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.jbspin.2006.11.003","volume":"74","author":"J Freeston","year":"2007","unstructured":"Freeston, J., Barkham, N., Hensor, E., Emery, P. & Fraser, A. Ankylosing spondylitis, HLA-B27 positivity and the need for biologic therapies. Joint Bone Spine 74(2), 140\u2013143 (2007).","journal-title":"Joint Bone Spine"},{"issue":"8","key":"91829_CR8","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1136\/ard.61.8.714","volume":"61","author":"G Vargas-Alarcon","year":"2002","unstructured":"Vargas-Alarcon, G. et al. Effect of HLA-B and HLA-DR genes on susceptibility to and severity of spondyloarthropathies in Mexican patients. Ann. Rheum. Dis. 61(8), 714\u2013717 (2002).","journal-title":"Ann. Rheum. Dis."},{"issue":"1","key":"91829_CR9","first-page":"78","volume":"7","author":"C Popescu","year":"2014","unstructured":"Popescu, C., Trandafir, M., Badica, A., Morar, F. & Predeteanu, D. Ankylosing spondylitis functional and activity indices in clinical practice. J. Med. Life. 7(1), 78\u201383 (2014).","journal-title":"J. Med. Life."},{"issue":"3","key":"91829_CR10","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1093\/rheumatology\/24.3.242","volume":"24","author":"HS Goie The","year":"1985","unstructured":"Goie The, H. S., Steven, M. M., van der Linden, S. M. & Cats, A. Evaluation of diagnostic criteria for ankylosing spondylitis: A comparison of the Rome, New York and modified New York criteria in patients with a positive clinical history screening test for ankylosing spondylitis. Br. J. Rheumatol. 24(3), 242\u2013249 (1985).","journal-title":"Br. J. Rheumatol."},{"issue":"6","key":"91829_CR11","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1136\/ard.2009.108233","volume":"68","author":"M Rudwaleit","year":"2009","unstructured":"Rudwaleit, M. et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): Validation and final selection. Ann. Rheum. Dis. 68(6), 777\u2013783 (2009).","journal-title":"Ann. Rheum. Dis."},{"issue":"5","key":"91829_CR12","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.semarthrit.2014.10.009","volume":"44","author":"A Boonen","year":"2015","unstructured":"Boonen, A. et al. The burden of non-radiographic axial spondyloarthritis. Semin. Arthritis Rheum. 44(5), 556\u2013562 (2015).","journal-title":"Semin. Arthritis Rheum."},{"issue":"1","key":"91829_CR13","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1136\/ard.2010.133645","volume":"70","author":"M Rudwaleit","year":"2011","unstructured":"Rudwaleit, M. et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann. Rheum. Dis. 70(1), 25\u201331 (2011).","journal-title":"Ann. Rheum. Dis."},{"issue":"6","key":"91829_CR14","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/j.berh.2018.08.008","volume":"31","author":"MM Lockwood","year":"2017","unstructured":"Lockwood, M. M. & Gensler, L. S. Nonradiographic axial spondyloarthritis. Best Pract. Res. 31(6), 816\u2013829 (2017).","journal-title":"Best Pract. Res."},{"issue":"4","key":"91829_CR15","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/j.semarthrit.2020.05.005","volume":"50","author":"GC Wright","year":"2020","unstructured":"Wright, G. C., Kaine, J. & Deodhar, A. Understanding differences between men and women with axial spondyloarthritis. Semin. Arthritis Rheum. 50(4), 687\u2013694 (2020).","journal-title":"Semin. Arthritis Rheum."},{"issue":"5","key":"91829_CR16","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.jbspin.2020.03.012","volume":"87","author":"M Arevalo","year":"2020","unstructured":"Arevalo, M. et al. Role of HLA-B27 in the comorbidities observed in axial spondyloarthritis: Data from COMOSPA. Joint Bone Spine 87(5), 445\u2013448 (2020).","journal-title":"Joint Bone Spine"},{"key":"91829_CR17","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s13075-016-1093-z","volume":"18","author":"JJ de Winter","year":"2016","unstructured":"de Winter, J. J., van Mens, L. J., van der Heijde, D., Landewe, R. & Baeten, D. L. Prevalence of peripheral and extra-articular disease in ankylosing spondylitis versus non-radiographic axial spondyloarthritis: A meta-analysis. Arthritis Res. Ther. 18, 196 (2016).","journal-title":"Arthritis Res. Ther."},{"issue":"12","key":"91829_CR18","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1136\/annrheumdis-2020-217941","volume":"79","author":"JT Rosenbaum","year":"2020","unstructured":"Rosenbaum, J. T. et al. Biologics, spondylitis and COVID-19. Ann Rheum Dis. 79(12), 1663\u20131665 (2020).","journal-title":"Ann Rheum Dis."},{"issue":"4","key":"91829_CR19","doi-asserted-by":"publisher","first-page":"621","DOI":"10.3899\/jrheum.200939","volume":"48","author":"JT Rosenbaum","year":"2021","unstructured":"Rosenbaum, J. T. et al. The effect of HLA-B27 on susceptibility and severity of COVID-19. J. Rheumatol. 48(4), 621\u2013622 (2021).","journal-title":"J. Rheumatol."},{"issue":"1","key":"91829_CR20","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1186\/s13075-018-1724-7","volume":"20","author":"M Arevalo","year":"2018","unstructured":"Arevalo, M. et al. Influence of HLA-B27 on the ankylosing spondylitis phenotype: Results from the REGISPONSER database. Arthritis Res. Ther. 20(1), 221 (2018).","journal-title":"Arthritis Res. Ther."},{"issue":"7","key":"91829_CR21","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1136\/annrheumdis-2012-202431","volume":"72","author":"IE van der Horst-Bruinsma","year":"2013","unstructured":"van der Horst-Bruinsma, I. E., Zack, D. J., Szumski, A. & Koenig, A. S. Female patients with ankylosing spondylitis: Analysis of the impact of gender across treatment studies. Ann. Rheum. Dis. 72(7), 1221\u20131224 (2013).","journal-title":"Ann. Rheum. Dis."},{"issue":"11","key":"91829_CR22","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1093\/aje\/kwh141","volume":"159","author":"KM Dunn","year":"2004","unstructured":"Dunn, K. M., Jordan, K., Lacey, R. J., Shapley, M. & Jinks, C. Patterns of consent in epidemiologic research: Evidence from over 25,000 responders. Am. J. Epidemiol. 159(11), 1087\u20131094 (2004).","journal-title":"Am. J. Epidemiol."},{"issue":"26","key":"91829_CR23","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1056\/NEJMp1303712","volume":"368","author":"P Croskerry","year":"2013","unstructured":"Croskerry, P. From mindless to mindful practice\u2013cognitive bias and clinical decision making. N. Engl. J. Med. 368(26), 2445\u20132448 (2013).","journal-title":"N. Engl. J. Med."},{"issue":"18","key":"91829_CR24","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1056\/NEJMp1606402","volume":"375","author":"AL Simpkin","year":"2016","unstructured":"Simpkin, A. L. & Schwartzstein, R. M. Tolerating uncertainty\u2014the next medical revolution?. N. Engl. J. Med. 375(18), 1713\u20131715 (2016).","journal-title":"N. Engl. J. Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91829-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91829-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91829-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T09:43:41Z","timestamp":1670060621000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91829-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,10]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["91829"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-91829-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,10]]},"assertion":[{"value":"23 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"CS, RH, and EA are employees of the Spondylitis Association of America. HH is the owner of Any-3 which donated web-based services. All other authors believe that they have no relevant competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12331"}}