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The continuum of axSpA ranges from nonradiographic axSpA (nr\u2010axSpA) to ankylosing spondylitis, also known as radiographic axSpA; the latter is defined by definitive radiographic sacroiliitis. Human leukocyte antigen B27 (HLA\u2010B27) is a genetic marker strongly associated with axSpA; it aids in the diagnosis of axSpA, and its absence leads to delay in diagnosis. For HLA\u2010B27\u2010negative patients, disease pathogenesis is poorly understood, signs and symptoms are frequently underrecognized, and diagnosis and treatment are commonly delayed. The proportion of HLA\u2010B27\u2010negative patients may be higher among non\u2010White patients and those with nr\u2010axSpA, who can face additional diagnostic challenges related to lack of definitive radiographic sacroiliitis. In this narrative review, we discuss the role of HLA\u2010B27 in the diagnosis and pathogenesis of axSpA and highlight various pathways and genes that may be related to axSpA pathogenesis in HLA\u2010B27\u2010negative patients. We also emphasize the need to characterize gut microbial communities in these patients. Adequate understanding of clinical and pathological features underlying HLA\u2010B27\u2010negative patients with axSpA will improve diagnosis, treatment, and outcomes for this complex inflammatory disease.<\/jats:p>","DOI":"10.1002\/acr2.11555","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T09:23:56Z","timestamp":1684920236000},"page":"333-344","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Human Leukocyte Antigen\n                    <scp>B27\u2010Negative<\/scp>\n                    Axial Spondyloarthritis: What Do We Know?"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2130-1246","authenticated-orcid":false,"given":"Atul","family":"Deodhar","sequence":"first","affiliation":[{"name":"Oregon Health &amp; Science University  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9567-3827","authenticated-orcid":false,"given":"Tejpal","family":"Gill","sequence":"additional","affiliation":[{"name":"Oregon Health &amp; Science University  Portland Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6520-5619","authenticated-orcid":false,"given":"Marina","family":"Magrey","sequence":"additional","affiliation":[{"name":"University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12913"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31591-4"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21621"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20990"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.104018"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.108233"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780270401"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0b013e318294457f"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-017-0640-1"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197304052881403"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/1179544117751627"},{"key":"e_1_2_13_13_1","first-page":"218","article-title":"Are gender\u2010specific approaches needed in diagnosing early axial spondyloarthritis?","volume":"20","author":"Ortolan A","year":"2018","journal-title":"Data from the SPondyloArthritis Caught Early cohort. 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