{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:35:21Z","timestamp":1787506521284,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess if microstructural bone lesions in individuals at risk of developing rheumatoid arthritis (RA) are related to the spectrum of anti\u2013modified protein antibodies (AMPAs) and affect the risk of developing RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cortical microchannels as well as cortical and trabecular bone mineral density (BMD) volumes (expressed as mg hydroxyapatite\/cm\n                      <jats:sup>3<\/jats:sup>\n                      ) were analyzed by high\u2010resolution peripheral quantitative computed tomography of the hand joints of individuals at risk of RA. AMPA response was profiled, including reactivities against citrullinated proteins (vimentin, enolase, and fibrinogen) as well as carbamylated and acetylated vimentin. All subjects were followed up for the development of RA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Subjects at risk of developing RA (n\u00a0=\u00a075) who had broad\u2010spectrum AMPAs (6\u20138 reactivities) had significantly more severe microstructural changes, including a higher mean\u2009\u00b1\u2009SD number of cortical microchannels per joint (95\u2009\u00b1\u20093) and lower total volumetric BMD (vBMD; 265\u2009\u00b1\u200945), trabecular vBMD (176\u2009\u00b1\u200942), and cortical vBMD (585\u2009\u00b1\u2009138), than those with moderate AMPA reactivity (3\u20135 reactivities) (number of cortical microchannels, 79\u2009\u00b1\u200930; total vBMD, 293\u2009\u00b1\u200933; trabecular vBMD, 195\u2009\u00b1\u200932; and cortical vBMD, 627 \u00b1 91) and those with narrow AMPA reactivity (1\u20132 reactivities) (number of cortical microchannels, 47\u2009\u00b1\u200920; total vBMD, 311\u2009\u00b1\u200934; trabecular vBMD, 211\u2009\u00b1\u200930; and cortical vBMD, 674\u2009\u00b1\u200956). Progressors to RA had significantly higher numbers of cortical microchannels (103\u2009\u00b1\u200930 versus 71\u2009\u00b1\u200935) and lower bone volume (258\u2009\u00b1\u200937 versus 295\u2009\u00b1\u200934) compared to nonprogressors. Furthermore, rate of progression to RA was high in subjects with broad AMPA reactivity (48%) versus those with medium AMPA reactivity (26%) or narrow AMPA reactivity (0%), as well as in those with a high number of cortical microchannels (44%) versus those with a low number of cortical microchannels (10%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Microstructural changes in individuals at risk of RA are associated with broad\u2010spectrum autoimmunity and predict the onset of RA. These data support the concept of structural priming of joints by autoimmunity before the onset of the inflammatory phase of the disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.41229","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T03:35:56Z","timestamp":1581996956000},"page":"418-426","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Microstructural Bone Changes Are Associated With\n                    <scp>Broad\u2010Spectrum<\/scp>\n                    Autoimmunity and Predict the Onset of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"74","author":[{"given":"David","family":"Simon","sequence":"first","affiliation":[{"name":"University Erlangen\u2013Nuremberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnd","family":"Kleyer","sequence":"additional","affiliation":[{"name":"University Erlangen\u2013Nuremberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duy Bui","family":"Cong","sequence":"additional","affiliation":[{"name":"University Erlangen\u2013Nuremberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Hueber","sequence":"additional","affiliation":[{"name":"University Erlangen\u2013Nuremberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Bang","sequence":"additional","affiliation":[{"name":"Orgentec Inc.  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Ramming","sequence":"additional","affiliation":[{"name":"University Erlangen\u2013Nuremberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Rech","sequence":"additional","affiliation":[{"name":"University Erlangen\u2013Nuremberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Schett","sequence":"additional","affiliation":[{"name":"University Erlangen\u2013Nuremberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.200"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209297"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11223"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37830"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200990"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207871"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209846"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-211325"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2016.05.002"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4511"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23763"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035296"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3579"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208887"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204543"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34344"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60975"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3158"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-212404"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202958"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40148"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.160647"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-018-0016-5"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09363-2"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/14397595.2016.1265907"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.135723"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.02.009"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7651"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208094"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208093"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40758"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20148128"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-11-255026"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208052"}],"container-title":["Arthritis &amp; 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