{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:11:12Z","timestamp":1789819872288,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T00:00:00Z","timestamp":1599436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To 1) determine the prevalence of anti\u2013cyclic citrullinated peptide 3 (anti\u2010CCP3) antibodies in anti\u2010CCP2 antibody\u2013positive (anti\u2010CCP2+) at\u2010risk individuals, and 2) explore the additional value of anti\u2010CCP3 antibodies in anti\u2010CCP2+ at\u2010risk individuals for predicting progression to inflammatory arthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Stored serum samples obtained from 347 anti\u2010CCP2+ (BioPlex 2200; Bio\u2010Rad) at\u2010risk individuals without clinical synovitis were tested for anti\u2010CCP3 antibodies. Anti\u2010CCP2 titers were categorized as low or high, and anti\u2010CCP3 titers were categorized as negative, low, or strong. Progression to inflammatory arthritis was defined as the development of clinical synovitis in \u22651 joint. Only subjects with \u22651 follow\u2010up visit were included in the progression analysis (n = 291).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the 347 samples included, anti\u2010CCP3 antibody titers tended to be either negative (n = 138 [39.7%]) or strongly positive (n =189 [54.4%]), with very few subjects showing a low titer (n = 20 [5.7%]). In contrast, for anti\u2010CCP2 antibodies, more low titers were observed (n = 103 [29.7%]). Eighty\u2010eight of 291 subjects (30.2%) developed inflammatory arthritis. The rate of progression to inflammatory arthritis in the low\u2010titer anti\u2010CCP2 group and the high\u2010titer anti\u2010CCP2 group fell from 7.5% to 3.3% and from 38.9% to 9.8%, respectively, when anti\u2010CCP3 was negative. Progression in the high\u2010titer anti\u2010CCP2 group increased from 38.9% to 48.4% when anti\u2010CCP3 was strongly positive. The area under the curve was 0.72 for anti\u2010CCP2 (95% confidence interval [95% CI] 0.66, 0.78) and 0.76 for anti\u2010CCP3 (95% CI 0.70, 0.81) for assessment of progression. In the multivariable analysis, the odds ratio for the development of inflammatory arthritis in anti\u2010CCP3+ subjects was 1.73 (95% CI 1.20, 2.51) (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Anti\u2010CCP3 antibodies improve the prediction of inflammatory arthritis in anti\u2010CCP2+ at\u2010risk individuals. The impact of anti\u2010CCP3 antibody status for the risk stratification of individuals with high\u2010titer anti\u2010CCP2 is particularly notable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.41402","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T10:00:14Z","timestamp":1592388014000},"page":"1820-1828","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Third\u2010Generation Anti\u2013Cyclic Citrullinated Peptide Antibodies Improve Prediction of Clinical Arthritis in Individuals at Risk of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0867-7051","authenticated-orcid":false,"given":"Andrea","family":"Di Matteo","sequence":"first","affiliation":[{"name":"University of Leeds NIHR Leeds Biomedical Research Centre Leeds Teaching Hospitals NHS Trust, Leeds, UK, and Polytechnic University of Marche Carlo Urbani Hospital  Jesi Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kulveer","family":"Mankia","sequence":"additional","affiliation":[{"name":"University of Leeds NIHR Leeds Biomedical Research Centre Leeds Teaching Hospitals NHS Trust  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Duquenne","sequence":"additional","affiliation":[{"name":"University of Leeds NIHR Leeds Biomedical Research Centre Leeds Teaching Hospitals NHS Trust  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mahler","sequence":"additional","affiliation":[{"name":"Inova Diagnostics, Inc.  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