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The current study was undertaken to assess the relationship between anti\u2010CarP antibodies and HLA<\/jats:styled-content>\u2013DRB<\/jats:styled-content>1<\/jats:italic> alleles in RA<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>Serum samples were obtained from 3 different collections, comprising a total of 1,126 RA<\/jats:styled-content> patients. Serum reactivity against in vitro carbamylated fetal calf serum proteins was determined by enzyme\u2010linked immunosorbent assay. HLA<\/jats:styled-content>\u2013DRB<\/jats:styled-content>1<\/jats:italic> alleles were determined using either hybridization techniques or imputation from HLA<\/jats:styled-content>\u2010dense genotypes. Results of these analyses were combined in a meta\u2010analysis with data from 3 previously reported cohorts. The carrier frequencies of the common HLA<\/jats:styled-content>\u2013DRB<\/jats:styled-content>1<\/jats:italic> alleles were compared between the antibody\u2010positive RA<\/jats:styled-content> subgroups and the double\u2010negative subgroup of RA<\/jats:styled-content> patients stratified by anti\u2013citrullinated protein antibody (ACPA<\/jats:styled-content>)\/anti\u2010CarP antibody status, and also between the 4 RA<\/jats:styled-content> patient strata and healthy controls.<\/jats:p><\/jats:sec>Results<\/jats:title>Meta\u2010analysis was conducted with 3,709 RA<\/jats:styled-content> patients and 2,305 healthy control subjects. Results revealed a significant increase in frequency of HLA<\/jats:styled-content>\u2013DRB<\/jats:styled-content>1*03<\/jats:italic> carriers in the ACPA<\/jats:styled-content>\u2212\/anti\u2010CarP+ subgroup as compared to ACPA<\/jats:styled-content>\u2212\/anti\u2010CarP\u2212 RA<\/jats:styled-content> patients and healthy controls; this was consistently found across the 6 sample collections. This association of HLA<\/jats:styled-content>\u2013DRB<\/jats:styled-content>1*03<\/jats:italic> with ACPA<\/jats:styled-content>\u2212\/anti\u2010CarP+ RA<\/jats:styled-content> was independent of the presence of the shared allele (SE<\/jats:styled-content><\/jats:italic>) and any other confounders analyzed. No other allele was specifically associated with the ACPA<\/jats:styled-content>\u2212\/anti\u2010CarP+ RA<\/jats:styled-content> patient subgroup. In contrast, frequency of the SE<\/jats:styled-content><\/jats:italic> was significantly increased in the ACPA<\/jats:styled-content>+\/anti\u2010CarP\u2212 and ACPA<\/jats:styled-content>+\/anti\u2010CarP+ RA<\/jats:styled-content> patient subgroups, without a significant distinction between them. Furthermore, some alleles (including HLA<\/jats:styled-content>\u2013DRB<\/jats:styled-content>1*03<\/jats:italic>) were associated with protection from ACPA<\/jats:styled-content>+ RA<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>These findings indicate a specific association of HLA<\/jats:styled-content>\u2013DRB<\/jats:styled-content>1*03<\/jats:italic> with ACPA<\/jats:styled-content>\u2212\/anti\u2010CarP+ RA<\/jats:styled-content>, suggesting that preferential presentation of carbamylated peptides could be a new mechanism underlying the contribution of HLA<\/jats:styled-content> alleles to RA<\/jats:styled-content> susceptibility.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40738","type":"journal-article","created":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T20:11:54Z","timestamp":1538424714000},"page":"331-339","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Specific Association of HLA<\/scp>\u2013DRB<\/scp>1*03<\/i> With Anti\u2013Carbamylated Protein Antibodies in Patients With Rheumatoid Arthritis"],"prefix":"10.1002","volume":"71","author":[{"given":"Cristina","family":"Regueiro","sequence":"first","affiliation":[{"name":"Instituto de Investigacion Sanitaria\u2013Hospital Cl\u00ednico Universitario de Santiago Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2869-7861","authenticated-orcid":false,"given":"Luis","family":"Rodr\u00edguez\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico San Carlos\u2013Instituto Investigaci\u00f3n Sanitaria San Carlos (IdISSC) Madr\u00edd Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Triguero\u2010Martinez","sequence":"additional","affiliation":[{"name":"Hospital Universitario de la Princesa, Instituto de Investigaci\u00f3n Sanitaria la Princesa (IIS-lP) 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