{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:01:57Z","timestamp":1792620117890,"version":"4.5.0"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001858","name":"VINNOVA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["90825"],"award-info":[{"award-number":["90825"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2023\u201002497;2023\u201001827"],"award-info":[{"award-number":["2023\u201002497;2023\u201001827"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Rheumatoid arthritis (RA)\u2013associated anticitrullinated protein antibodies (ACPAs) target various antigens by binding short citrulline amino acid motifs, resulting in heterogeneous ACPA profiles among patients. Here we analyzed ACPA patterns by recognized citrulline motifs in relation to the RA risk factors HLA\u2010DRB1 shared epitope (SE) alleles and history of smoking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rheumatoid factor (RF) and anticyclic citrullinated peptide (CCP2) isotypes, 15 anti\u2010Cit\u2010 and four anti\u2010Carb\/Acet\u2010peptide\u2010IgG, were centrally measured in 6,907 patients from five Scandinavian RA cohorts using fluoroenzyme immunoassay and a custom\u2010made multiplex solid\u2010phase microarray. HLA\u2010DRB1 SE alleles were imputed from single\u2010nucleotide polymorphism genotyping data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Single\u2010citrulline peptides derived from four multicitrulline peptides (Cit Fib\u03b1<jats:sub>36\u201050<\/jats:sub>, Cit Fib\u03b2<jats:sub>60\u201074,<\/jats:sub> Cit TNC5, and Cit Vim<jats:sub>60\u201075<\/jats:sub>) showed differential binding patterns, supporting recognition of citrulline motifs rather than long peptides. Four citrulline peptides (Cit Fib\u03b2<jats:sub>36\u201052<\/jats:sub>, Cit Fib\u03b2<jats:sub>60\u201074\u2010Cit3<\/jats:sub>, Cit Fil<jats:sub>307\u2010324<\/jats:sub>, and Cit Vim<jats:sub>60\u201075\u2010Cit1<\/jats:sub>) captured 97% of IgG anti\u2010CCP2+ patients. Patient subsets based on ACPA, anti\u2010Carb\/Acet, and RF displayed differences in ACPA composition and disease activity but not comorbidities. Different ACPAs overlapped, but when dichotomizing patients based on high reactivity to peptide citrulline motifs, only ACPA to nonglycine citrulline motif associated with HLA SE alleles. In IgG anti\u2010CCP2+ patients, 90% of those with only high nonglycine ACPA were HLA SE allele carriers compared with 67% in the group with glycine motif\u2013only ACPA (odds ratio 4.5). Smoking status associated with IgA and glycine motif ACPA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although citrulline\u2010glycine motifs are prevalent ACPA targets, our data reveal that HLA SE alleles are primarily associated with ACPA to nonglycine citrulline motifs, providing insight in ACPA T cell dependance. Yet, the etiologic significance of ACPA targeting different protein structures remains unknown.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.43161","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T08:37:26Z","timestamp":1742719046000},"page":"1179-1193","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Recognition of Glycine Versus Nonglycine Citrulline Motifs Dictating the <scp>HLA<\/scp> Class <scp>II<\/scp> Association of Anticitrullinated Protein Antibodies: Insights From Autoantibody Profiling of 6,900 Scandinavian Patients With Rheumatoid Arthritis"],"prefix":"10.1002","volume":"77","author":[{"given":"Linda","family":"Mathsson Alm","sequence":"first","affiliation":[{"name":"Uppsala University and Thermo Fisher Scientific  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3380-5342","authenticated-orcid":false,"given":"Helga","family":"Westerlind","sequence":"additional","affiliation":[{"name":"Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Gehring","sequence":"additional","affiliation":[{"name":"Thermo Fisher Scientific  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Hansson","sequence":"additional","affiliation":[{"name":"Karolinska Institutet, Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Ghasemzadeh","sequence":"additional","affiliation":[{"name":"Thermo Fisher Scientific  Uppsala 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