{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:32:25Z","timestamp":1791340345539,"version":"4.3.1"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,5,25]],"date-time":"2015-05-25T00:00:00Z","timestamp":1432512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Agence Nationale pour la Recherche","award":["GEMISA"],"award-info":[{"award-number":["GEMISA"]}]},{"name":"Arthritis Fondation Courtin","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Soci\u00e9t\u00e9 Fran\u00e7aise de Rhumatologie","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Several polymorphisms in\n                      <jats:italic>ERAP1<\/jats:italic>\n                      are strongly associated with susceptibility to spondyloarthritis (SpA). The combination of rs17482078, rs10050860, and rs30187 results in the construction of 3 major haplotypes that are associated with SpA (the \u201cprotective\u201d haplotype T\/T\/C, the \u201cneutral\u201d haplotype C\/C\/C, and the \u201csusceptibility\u201d haplotype C\/C\/T). The aim of the present study was to determine whether such haplotypes might affect endoplasmic reticulum aminopeptidase 1 (ERAP\u20101) messenger RNA (mRNA) expression, protein level, and\/or enzymatic activity in antigen\u2010presenting cells, a type of cell that is potentially relevant to disease pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Monocyte\u2010derived dendritic cells (DCs) were generated in 2 cohorts (a discovery cohort and a replication cohort) comprising a total of 23 SpA patients and 44 healthy controls. Lymphoblastoid B cell lines were established from individuals who were homozygous for the risk, the neutral, or the protective\n                      <jats:italic>ERAP1<\/jats:italic>\n                      haplotype, respectively. In those samples, we investigated the relationship between\n                      <jats:italic>ERAP1<\/jats:italic>\n                      haplotypes and mRNA expression level. We also used Western blot analysis to measure the relative protein expression of ERAP\u20101 and a fluorogenic assay to measure its enzymatic activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In monocyte\u2010derived DCs, there was a strong association between\n                      <jats:italic>ERAP1<\/jats:italic>\n                      haplotypes and the ERAP\u20101 mRNA expression level, with higher levels in subjects harboring the susceptibility haplotype (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.001 and\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20095.6 \u00d7 10\n                      <jats:sup>\u22127<\/jats:sup>\n                      in the discovery and replication cohorts, respectively). In lymphoblastoid B cell lines, we observed a significant correlation between haplotype risk score and\n                      <jats:italic>ERAP1<\/jats:italic>\n                      transcript or protein level (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.003, \u03c1\u2009=\u20090.92 for both). Enzymatic activity followed a similar trend both in monocyte\u2010derived DCs and in lymphoblastoid B cell lines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These data provide strong evidence that SpA\u2010associated\n                      <jats:italic>ERAP1<\/jats:italic>\n                      polymorphisms affect the level of gene expression in antigen\u2010presenting cells. How increased production\/activity of ERAP\u20101 may influence susceptibility to SpA remains to be determined.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.39072","type":"journal-article","created":{"date-parts":[[2015,3,4]],"date-time":"2015-03-04T10:01:34Z","timestamp":1425463294000},"page":"1525-1534","source":"Crossref","is-referenced-by-count":68,"title":["<i>ERAP1<\/i>\n                    Gene Expression Is Influenced by Nonsynonymous Polymorphisms Associated With Predisposition to Spondyloarthritis"],"prefix":"10.1002","volume":"67","author":[{"given":"F\u00e9licie","family":"Costantino","sequence":"first","affiliation":[{"name":"INSERM U1173, Universit\u00e9 de Versailles St. Quentin\u2010en\u2010Yvelines, and Laboratoire d'Excellence INFLAMEX, Paris, France and H\u00f4pital Ambroise Par\u00e9, AP\u2010HP Boulogne\u2010Billancourt France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Talpin","sequence":"additional","affiliation":[{"name":"INSERM U1173, Universit\u00e9 de Versailles St. Quentin\u2010en\u2010Yvelines, and Laboratoire d'Excellence INFLAMEX Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irini","family":"Evnouchidou","sequence":"additional","affiliation":[{"name":"INSERM U1151, CNRS (UMR 8253), Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Kadi","sequence":"additional","affiliation":[{"name":"INSERM U1173, Universit\u00e9 de Versailles St. Quentin\u2010en\u2010Yvelines, and Laboratoire d'Excellence INFLAMEX Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Leboime","sequence":"additional","affiliation":[{"name":"H\u00f4pital Ambroise Par\u00e9, AP\u2010HP Boulogne\u2010Billancourt France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roula","family":"Said\u2010Nahal","sequence":"additional","affiliation":[{"name":"H\u00f4pital Ambroise Par\u00e9, AP\u2010HP Boulogne\u2010Billancourt France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Bonilla","sequence":"additional","affiliation":[{"name":"INSERM U1173, Universit\u00e9 de Versailles St. Quentin\u2010en\u2010Yvelines, and Laboratoire d'Excellence INFLAMEX Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Letourneur","sequence":"additional","affiliation":[{"name":"Institut Cochin, INSERM U1016, CNRS (UMR8104) and Universit\u00e9 Paris Descartes Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tifenn","family":"Leturcq","sequence":"additional","affiliation":[{"name":"INSERM U1173, Universit\u00e9 de Versailles St. Quentin\u2010en\u2010Yvelines, and Laboratoire d'Excellence INFLAMEX Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyna","family":"Ka","sequence":"additional","affiliation":[{"name":"INSERM U1173, Universit\u00e9 de Versailles St. Quentin\u2010en\u2010Yvelines, and Laboratoire d'Excellence INFLAMEX Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van Endert","sequence":"additional","affiliation":[{"name":"INSERM U1151, CNRS (UMR 8253), Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri\u2010Jean","family":"Garchon","sequence":"additional","affiliation":[{"name":"INSERM U1173, Universit\u00e9 de Versailles St. Quentin\u2010en\u2010Yvelines, and Laboratoire d'Excellence INFLAMEX, Paris, France and H\u00f4pital Ambroise Par\u00e9, AP\u2010HP Boulogne\u2010Billancourt France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Chiocchia","sequence":"additional","affiliation":[{"name":"INSERM U1173, Universit\u00e9 de Versailles St. Quentin\u2010en\u2010Yvelines, and Laboratoire d'Excellence INFLAMEX Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Breban","sequence":"additional","affiliation":[{"name":"INSERM U1173, Universit\u00e9 de Versailles St. Quentin\u2010en\u2010Yvelines, and Laboratoire d'Excellence INFLAMEX, Paris, France and H\u00f4pital Ambroise Par\u00e9, AP\u2010HP Boulogne\u2010Billancourt France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204436"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","unstructured":"Said\u2010NahalR Miceli\u2010RichardC BerthelotJM DucheA Dernis\u2010LabousE Le BlevecG et al on behalf ofGroupe Fran\u00e7ais d'Etude G\u00e9n\u00e9tique des Spondylarthropathies.The familial form of spondylarthropathy: a clinical study of 115 multiplex families [published erratum appears in Arthritis Rheum 2000; 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