{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:08:24Z","timestamp":1790766504627,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T00:00:00Z","timestamp":1595289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["ING20130526783"],"award-info":[{"award-number":["ING20130526783"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Soci\u00e9t\u00e9 Fran\u00e7aise de Rhumatologie"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>It was previously shown that <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B27 subtypes predisposing to spondyloarthritis (SpA), i.e., B*27:02, B*27:05, and B*27:07, displayed an increased propensity to form intracellular oligomers and to accumulate at a high density in cytoplasmic vesicles, as compared to the non\u2013SpA\u2010associated <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B*07:02 and <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B*27:06. This study was undertaken to characterize the nature and content of <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B\u2013containing vesicles and to further examine their relevance to SpA predisposition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Vesicles containing <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B proteins were detected in transfected HeLa cells and in cells from SpA patients or <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B27\/human \u03b2<jats:sub>2<\/jats:sub>\u2010microglobulin (h\u03b2<jats:sub>2<\/jats:sub>m)\u2013transgenic rats, by microscopy. The nature and content of <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B\u2013containing vesicles were characterized in colocalization experiments with appropriate markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The SpA\u2010associated <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B*27:04 subtype accumulated at higher levels (<jats:italic>P<\/jats:italic> &lt; 10<jats:sup>\u22125<\/jats:sup>) in cytoplasmic vesicles compared to <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B*27:06, from which it differs only by 2 substitutions, reinforcing the correlation between vesicle formation and SpA predisposition. Colocalization studies showed that those vesicles contained misfolded <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B heavy chain along with \u03b2<jats:sub>2<\/jats:sub>m and endoplasmic reticulum (<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>) chaperones (calnexin, calreticulin, BiP, glucose\u2010regulated protein 94\u2010kd) and belonged to the <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> but were distinct from the peptide\u2010loading complex (<jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>). Similar vesicles were observed in immune cells from <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B27+ SpA patients, in greater abundance than in healthy controls (<jats:italic>P<\/jats:italic> &lt; 0.01), and in dendritic cells from <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B27\/h\u03b2<jats:sub>2<\/jats:sub>m transgenic rats, correlating with SpA susceptibility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Accumulation of misfolded <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B heavy chain along with \u03b2<jats:sub>2<\/jats:sub>m and <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> chaperones into <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\u2010derived vesicles distinct from the <jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content> is a characteristic feature of <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B27 subtypes predisposing to SpA. This phenomenon could contribute to <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2013B27 pathogenicity, via a noncanonical mechanism.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41281","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T07:38:25Z","timestamp":1586417905000},"page":"1534-1546","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["<scp>HLA<\/scp>\u2013B27 Subtypes Predisposing to Ankylosing Spondylitis Accumulate in an Endoplasmic Reticulum\u2013Derived Compartment Apart From the Peptide\u2010Loading Complex"],"prefix":"10.1002","volume":"72","author":[{"given":"Nad\u00e8ge","family":"Jah","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay, Universite\u2032 de Versailles St.\u2010Quentin\u2010en\u2010Yvelines, INSERM (UMR 1173), Montigny\u2010Le\u2010Bretonneux, France, and Laboratoire d\u2019Excellence INFLAMEX, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude","family":"Jobart\u2010Malfait","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay, Universite\u2032 de Versailles St.\u2010Quentin\u2010en\u2010Yvelines, INSERM (UMR 1173), Montigny\u2010Le\u2010Bretonneux, France, and Laboratoire d\u2019Excellence INFLAMEX, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketia","family":"Ermoza","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay, Universite\u2032 de Versailles St.\u2010Quentin\u2010en\u2010Yvelines, INSERM (UMR 1173), Montigny\u2010Le\u2010Bretonneux, France, and Laboratoire d\u2019Excellence INFLAMEX, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Noteuil","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay, Universite\u2032 de Versailles St.\u2010Quentin\u2010en\u2010Yvelines, INSERM (UMR 1173), Montigny\u2010Le\u2010Bretonneux, France, and Laboratoire d\u2019Excellence INFLAMEX, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Chiocchia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6932-9395","authenticated-orcid":false,"given":"Maxime","family":"Breban","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay, Universite\u2032 de Versailles St.\u2010Quentin\u2010en\u2010Yvelines, INSERM (UMR 1173), Montigny\u2010Le\u2010Bretonneux, France, Laboratoire d\u2019Excellence INFLAMEX, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9, Paris, France, and H\u00f4pital Ambroise Par\u00e9, AP\u2010HP  Boulogne\u2010Billancourt France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay, Universite\u2032 de Versailles St.\u2010Quentin\u2010en\u2010Yvelines, INSERM (UMR 1173), Montigny\u2010Le\u2010Bretonneux, France, and Laboratoire d\u2019Excellence INFLAMEX, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1406182"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22807"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112110"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-017-0640-1"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2012.01944.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-015-0516-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10948"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22725"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38644"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.108233"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39072"},{"key":"e_1_2_7_13_1","first-page":"2466","article-title":"L\u00f3pez de Castro JA. 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