{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T10:11:25Z","timestamp":1766830285994,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>The strong genetic association between HLA-B*27 and spondyloarthritis (SpA) accounts for about 90% of the susceptibility to axial SpA (axSpA), and the presence of HLA-B*27 is helpful in classifying patients according to the Assessment of SpondyloArthritis International Society (ASAS) classification criteria. However, over the years, other HLA-B alleles have been associated with an increased risk of developing SpA; on this basis, the aim of our study was to describe the demographic, clinical, and radiological characteristics of a cohort of SpA patients who were negative for HLA-B*27. We identified 85 patients with a clinical diagnosis of SpA displaying HLA-B alleles other than HLA-B*27; HLA-B*51 emerged as the most prevalent allele (N = 33, 39%), regardless of the fulfilment of either the axial or the peripheral ASAS criteria. The second most prevalent allele in the full cohort (N = 16, 19%) and in the patients fulfilling either the axial or the peripheral criteria was HLA-B*35. The third most prevalent allele in the full cohort was HLA-B*18 (N = 12, 15%), which was also the second most prevalent allele in the patients fulfilling neither of the two sets of criteria. Overall, the clinical picture was similar across the subgroups fulfilling the different sets of ASAS criteria; however, the patients not fulfilling any ASAS criteria had a higher likelihood of having arthritis compared to the patients fulfilling the axial criteria, whereas the Bath Ankylosing Spondylitis Functional Index was significantly higher in those patients fulfilling the axial criteria compared to those who did not fulfill any criteria. Our results indicate that other HLA alleles, beyond HLA-B*27, could be useful in facilitating SpA diagnosis, particularly in patients with a clinical picture which is consistent with SpA but does not fulfill the ASAS classification criteria.<\/jats:p>","DOI":"10.3390\/diagnostics13233550","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T07:40:01Z","timestamp":1701157201000},"page":"3550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Human Leukocyte Antigen B*27-Negative Spondyloarthritis: Clinical, Serological, and Radiological Features of a Single-Center Cohort"],"prefix":"10.3390","volume":"13","author":[{"given":"Francesco Maria","family":"Mariani","sequence":"first","affiliation":[{"name":"Internal Medicine and Nephrology Division, ASL1 Avezzano-Sulmona-L\u2019Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1105-5640","authenticated-orcid":false,"given":"Alessia","family":"Alunno","sequence":"additional","affiliation":[{"name":"Internal Medicine and Nephrology Division, ASL1 Avezzano-Sulmona-L\u2019Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evy","family":"Di Ruscio","sequence":"additional","affiliation":[{"name":"Internal Medicine and Nephrology Division, ASL1 Avezzano-Sulmona-L\u2019Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piera","family":"Altieri","sequence":"additional","affiliation":[{"name":"Internal Medicine and Nephrology Division, ASL1 Avezzano-Sulmona-L\u2019Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3594-2503","authenticated-orcid":false,"given":"Claudio","family":"Ferri","sequence":"additional","affiliation":[{"name":"Internal Medicine and Nephrology Division, ASL1 Avezzano-Sulmona-L\u2019Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1958-5136","authenticated-orcid":false,"given":"Francesco","family":"Carubbi","sequence":"additional","affiliation":[{"name":"Internal Medicine and Nephrology Division, ASL1 Avezzano-Sulmona-L\u2019Aquila, Department of Clinical Medicine, Life, Health & Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1056\/NEJMra1406182","article-title":"Ankylosing Spondylitis and Axial Spondyloarthritis","volume":"374","author":"Taurog","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e001136","DOI":"10.1136\/rmdopen-2019-001136","article-title":"Peripheral Spondyloarthritis: A Neglected Entity-State of the Art","volume":"6","author":"Carron","year":"2020","journal-title":"RMD Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0140-6736(16)31591-4","article-title":"Axial Spondyloarthritis","volume":"390","author":"Sieper","year":"2017","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/s41584-020-00552-4","article-title":"Axial Spondyloarthritis: Concept, Construct, Classification and Implications for Therapy","volume":"17","author":"Robinson","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"601518","DOI":"10.3389\/fimmu.2021.601518","article-title":"Spondyloarthritis and the Human Leukocyte Antigen (HLA)-B(*)27 Connection","volume":"12","author":"Kavadichanda","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1136\/ard.2009.108233","article-title":"The Development of Assessment of SpondyloArthritis International Society Classification Criteria for Axial Spondyloarthritis (Part II): Validation and Final Selection","volume":"68","author":"Rudwaleit","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1136\/ard.2010.133645","article-title":"The Assessment of SpondyloArthritis International Society Classification Criteria for Peripheral Spondyloarthritis and for Spondyloarthritis in General","volume":"70","author":"Rudwaleit","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s10067-014-2661-8","article-title":"Axial Spondyloarthritis Criteria and Modified NY Criteria: Issues and Controversies","volume":"33","author":"Deodhar","year":"2014","journal-title":"Clin. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e001681","DOI":"10.1136\/rmdopen-2021-001681","article-title":"Sex-Associated and Gender-Associated Differences in the Diagnosis and Management of Axial Spondyloarthritis: Addressing the Unmet Needs of Female Patients","volume":"7","author":"Chimenti","year":"2021","journal-title":"RMD Open"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Del Vescovo, S., Venerito, V., Iannone, C., and Lopalco, G. (2023). Uncovering the Underworld of Axial Spondyloarthritis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076463"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1007\/s11926-015-0516-1","article-title":"Revisiting MHC Genes in Spondyloarthritis","volume":"17","author":"Breban","year":"2015","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/intimm\/dxw002","article-title":"Genetics of Autoimmune Diseases: Perspectives from Genome-Wide Association Studies","volume":"28","author":"Kochi","year":"2016","journal-title":"Int. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s13075-018-1724-7","article-title":"Influence of HLA-B27 on the Ankylosing Spondylitis Phenotype: Results from the REGISPONSER Database","volume":"20","author":"Moreno","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1136\/ard.2011.152975","article-title":"HLA-B27 Positive Patients Differ from HLA-B27 Negative Patients in Clinical Presentation and Imaging: Results from the DESIR Cohort of Patients with Recent Onset Axial Spondyloarthritis","volume":"70","author":"Chung","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_15","first-page":"735","article-title":"Non-HLA Genes in Ankylosing Spondylitis: What Meta-Analyses Have Shown?","volume":"32","author":"Chatzikyriakidou","year":"2014","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"671682","DOI":"10.3389\/fgene.2021.671682","article-title":"Genetics of Ankylosing Spondylitis-Focusing on the Ethnic Difference Between East Asia and Europe","volume":"12","author":"Wu","year":"2021","journal-title":"Front. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7146","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":"ref_18","doi-asserted-by":"crossref","first-page":"e163","DOI":"10.1038\/cti.2017.49","article-title":"Progress of Genome-Wide Association Studies of Ankylosing Spondylitis","volume":"6","author":"Li","year":"2017","journal-title":"Clin. Transl. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e001250","DOI":"10.1136\/rmdopen-2020-001250","article-title":"Association of ERAP2 Polymorphisms in Colombian HLA-B27+ or HLA-B15+ Patients with SpA and Its Relationship with Clinical Presentation: Axial or Peripheral Predominance","volume":"6","author":"Londono","year":"2020","journal-title":"RMD Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s13075-015-0640-3","article-title":"Concepts of Pathogenesis in Psoriatic Arthritis: Genotype Determines Clinical Phenotype","volume":"17","author":"FitzGerald","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/S0016-5085(00)70209-5","article-title":"Clinical Phenotype Is Related to HLA Genotype in the Peripheral Arthropathies of Inflammatory Bowel Disease","volume":"118","author":"Orchard","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103443","DOI":"10.1016\/j.autrev.2023.103443","article-title":"SpA plus IBD or IBD plus SpA: Does Commutative Property Apply?","volume":"22","author":"Carubbi","year":"2023","journal-title":"Autoimmun. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S28","DOI":"10.1002\/ibd.20726","article-title":"Do HLA Antigens Predict the Occurrence of Extraintestinal Manifestations of IBD?","volume":"14","author":"Jewell","year":"2008","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/978-1-4939-2690-9_19","article-title":"Luminex-Based Methods in High-Resolution HLA Typing","volume":"1310","author":"Testi","year":"2015","journal-title":"Mol. Typing Blood Cell Antigens"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1136\/ard.2008.094870","article-title":"Development of an ASAS-Endorsed Disease Activity Score (ASDAS) in Patients with Ankylosing Spondylitis","volume":"68","author":"Lukas","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_26","first-page":"2286","article-title":"A New Approach to Defining Disease Status in Ankylosing Spondylitis: The Bath Ankylosing Spondylitis Disease Activity Index","volume":"21","author":"Garrett","year":"1994","journal-title":"J. Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1136\/ard.62.2.127","article-title":"Assessment of Enthesitis in Ankylosing Spondylitis","volume":"62","author":"Spoorenberg","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/art.23568","article-title":"Measuring Clinical Enthesitis in Psoriatic Arthritis: Assessment of Existing Measures and Development of an Instrument Specific to Psoriatic Arthritis","volume":"59","author":"Healy","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2147\/PPA.S162420","article-title":"Patient-Reported Outcomes in European Spondyloarthritis Patients: A Systematic Review of the Literature","volume":"12","author":"Queiro","year":"2018","journal-title":"Patient Prefer. Adherence"},{"key":"ref_30","first-page":"2281","article-title":"A New Approach to Defining Functional Ability in Ankylosing Spondylitis: The Development of the Bath Ankylosing Spondylitis Functional Index","volume":"21","author":"Calin","year":"1994","journal-title":"J. Rheumatol."},{"key":"ref_31","first-page":"S14","article-title":"The Health Assessment Questionnaire (HAQ)","volume":"23","author":"Bruce","year":"2005","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1186\/s13075-016-1151-6","article-title":"Patient Global Assessment in Measuring Disease Activity in Rheumatoid Arthritis: A Review of the Literature","volume":"18","author":"Nikiphorou","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_33","first-page":"e088","article-title":"Validation of Digital Visual Analog Scale Pain Scoring with a Traditional Paper-Based Visual Analog Scale in Adults","volume":"2","author":"Delgado","year":"2018","journal-title":"J. Am. Acad. Orthop. Surg. Glob. Res. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/acr2.11555","article-title":"Human Leukocyte Antigen B27-Negative Axial Spondyloarthritis: What Do We Know?","volume":"5","author":"Deodhar","year":"2023","journal-title":"ACR Open Rheumatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1007\/s00296-017-3741-2","article-title":"Association of HLA-B27 with Ankylosing Spondylitis and Clinical Features of the HLA-B27-Associated Ankylosing Spondylitis: A Meta-Analysis","volume":"37","author":"Lin","year":"2017","journal-title":"Rheumatol. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s40744-018-0100-z","article-title":"Role of Human Leukocyte Antigens (HLA) in Autoimmune Diseases","volume":"5","author":"Bodis","year":"2018","journal-title":"Rheumatol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1007\/s10067-020-04999-4","article-title":"The Occurrence of Sacroiliitis in HLA-B*35-Positive Patients with Undifferentiated Spondyloarthritis. A Cross Sectional MRI Study","volume":"39","year":"2020","journal-title":"Clin. Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.clim.2016.07.019","article-title":"Implications of the Diversity of Class I HLA Associations in Psoriatic Arthritis","volume":"172","author":"Winchester","year":"2016","journal-title":"Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"182","DOI":"10.2169\/internalmedicine.39.182","article-title":"Reiter\u2019s Syndrome Associated with HLA-B51","volume":"39","author":"Shimamoto","year":"2000","journal-title":"Intern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1177\/147323000303100109","article-title":"Reiter\u2019s Syndrome Associated with HLA-B51: A Case Report","volume":"31","author":"Taniguchi","year":"2003","journal-title":"J. Int. Med. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1093\/rheumatology\/kep363","article-title":"HLA-B51-Related Seronegative Spondyloarthropathy Associated with Membranous Nephropathy","volume":"49","author":"Horino","year":"2010","journal-title":"Rheumatology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"992","DOI":"10.12998\/wjcc.v10.i3.992","article-title":"Occurrence of Human Leukocyte Antigen B51-Related Ankylosing Spondylitis in a Family: Two Case Reports","volume":"10","author":"Lim","year":"2022","journal-title":"World J. Clin. Cases"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1136\/ard.53.11.755","article-title":"HLA-B Alleles and Complotypes in Mexican Patients with Seronegative Spondyloarthropathies","volume":"53","author":"Garcia","year":"1994","journal-title":"Ann. Rheum. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"524","DOI":"10.3346\/jkms.2002.17.4.524","article-title":"The Comparison between Beh\u00e7et\u2019s Disease and Spondyloarthritides: Does Beh\u00e7et\u2019s Disease belong to the Spondyloarthropathy Complex?","volume":"17","author":"Chang","year":"2002","journal-title":"J. Korean Med. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"329","DOI":"10.3109\/s10165-005-0414-x","article-title":"A Study of Ten Japanese Patients with Seronegative Spondylarthropathy: A Tentative Proposal","volume":"15","author":"Higashi","year":"2005","journal-title":"Mod. Rheumatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/j.1346-8138.2005.tb00807.x","article-title":"Psoriasis Arthropathy and HLA-B51: Report of 5 Cases","volume":"32","author":"Yamamoto","year":"2005","journal-title":"J. Dermatol."},{"key":"ref_47","first-page":"208","article-title":"MHC Class I and Class II Genes in Tunisian Patients with Reactive and Undifferentiated Arthritis","volume":"27","author":"Siala","year":"2009","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"321","DOI":"10.47102\/annals-acadmedsg.V48N10p321","article-title":"Clinical Findings of Ankylosing Spondylitis with and Without Human Leukocyte Antigen (HLA)-B27 and HLA-B51","volume":"48","author":"Jung","year":"2019","journal-title":"Ann. Acad. Med. Singap."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/23\/3550\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:32:29Z","timestamp":1760131949000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/23\/3550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,28]]},"references-count":48,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["diagnostics13233550"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13233550","relation":{},"ISSN":["2075-4418"],"issn-type":[{"type":"electronic","value":"2075-4418"}],"subject":[],"published":{"date-parts":[[2023,11,28]]}}}