{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:01:16Z","timestamp":1790154076390,"version":"4.0.1"},"reference-count":133,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["75N93019C00068"],"award-info":[{"award-number":["75N93019C00068"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunological Reviews"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Rheumatoid Arthritis (RA) is a prevalent form of inflammatory arthritis in which post\u2010translational modifications are known to play a major role in the loss of tolerance. This review summarizes current knowledge of the role that such modifications play in the disease. Most individuals with RA have antibody responses directed against citrullinated and\/or carbamylated self\u2010antigens, but additional modifications are under active investigation. Post\u2010translational modifications can alter the primary protein sequence, increasing binding to HLA molecules and recognition by T cells, and can generate new epitopes that are recognized by autoantibodies. They can also perturb protein structure and alter protein processing, enhancing presentation of cryptic epitopes. Finally, these modifications can alter protein function, potentially undermining cellular identity and function. Potentiation of post\u2010translational modifications has been directly linked to environmental exposures that are epidemiologically tied to RA risk. The immunogenic effects of protein modification are associated with key variants that confer genetic risk for RA. Notably, immune assays designed to measure antibody recognition and monitor T cell responses directed against citrullinated and carbamylated antigens have emerged as useful biomarkers of disease risk and activity. The pathways of protein citrullination and carbamylation are also important targets for potential preventative and curative therapies.<\/jats:p>","DOI":"10.1111\/imr.70178","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:09:59Z","timestamp":1789452599000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Autoantibodies and T Cells Target Citrullinated and Homocitrullinated Antigens in Rheumatoid Arthritis"],"prefix":"10.1111","volume":"342","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7217-5729","authenticated-orcid":false,"given":"Eddie A.","family":"James","sequence":"first","affiliation":[{"name":"Center for Translational Immunology Benaroya Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6246-0088","authenticated-orcid":false,"given":"Aisha","family":"Callebaut","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology Benaroya Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9005-1885","authenticated-orcid":false,"given":"Jane H.","family":"Buckner","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology Benaroya Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4843-4599","authenticated-orcid":false,"given":"William W.","family":"Kwok","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology Benaroya Research Institute  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.138461"},{"issue":"4","key":"e_1_2_11_3_1","first-page":"286","article-title":"Extra\u2010Articular Manifestations in Rheumatoid Arthritis","volume":"5","author":"Cojocaru M.","year":"2010","journal-title":"Maedica (Bucur)"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204627"},{"issue":"5","key":"e_1_2_11_5_1","first-page":"S43","article-title":"The Consequences of Rheumatoid Arthritis: Quality of Life Measures in the Individual Patient","volume":"23","author":"Pollard L.","year":"2005","journal-title":"Clinical and Experimental Rheumatology"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199500501-00003"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205428"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/728610"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40218"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780301102"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035075"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.085084"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1733"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.750753"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2011.06.010"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1010"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108078"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead260"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38637"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43091-8"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1114465108"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2017.12.002"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S528487"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413290"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36620-y"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501241200"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8148"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2024.101355"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb799"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27439"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20279-w"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002549"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15313"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.23.4.302"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116713"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.50.9.611"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200001)43:1<155::AID-ANR20>3.0.CO;2-3"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.2.538"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27594"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-0409-1"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22983"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209248"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abd2688"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00192"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102163"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2013.10.008"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0536-2"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000075"},{"issue":"4","key":"e_1_2_11_49_1","first-page":"2923","article-title":"Protein Acetylation and Deacetylation: An Important Regulatory Modification in Gene Transcription (Review)","volume":"20","author":"Xia C.","year":"2020","journal-title":"Experimental and Therapeutic Medicine"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-018-0116-z"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1741730"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2019.02.007"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X211022533"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.162"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42098"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24129884"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220500"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.160964"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2023.100540"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6097417"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1447"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40744-022-00427-y"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131241"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.001013"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00494"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.145217"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abe0896"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31750-1"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20230209"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3625"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-020520-111016"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1159\/000522331"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.139388"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.801076"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005580"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2017.04.007"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40401"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aag3358"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.2217\/ijr.14.23"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28756"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2012.03.006"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2011.01.014"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0520-x"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keae358"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e32835fb8ec"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093329"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916934.2018.1527907"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep11969"},{"issue":"8","key":"e_1_2_11_89_1","first-page":"868","article-title":"Neutrophil Extracellular Trap Formation\u2010Derived Peptidylarginine Deiminases in the Citrullination of Oral Bacteria to Promote Inflammation in Rheumatoid Arthritis","volume":"53","author":"Acharya S.","year":"2026","journal-title":"Journal of Rheumatology"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4439"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.76"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plabm.2024.e00420"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.130742"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14051529"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11181"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21269"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035296"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40578"},{"key":"e_1_2_11_99_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40590"},{"key":"e_1_2_11_100_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8476"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400704"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3848"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12825"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keg230"},{"key":"e_1_2_11_105_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.25064"},{"key":"e_1_2_11_106_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-013-2731-2"},{"key":"e_1_2_11_107_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30445"},{"key":"e_1_2_11_108_1","doi-asserted-by":"publisher","DOI":"10.4110\/in.2013.13.4.116"},{"key":"e_1_2_11_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.04.004"},{"issue":"6","key":"e_1_2_11_110_1","first-page":"326","article-title":"Antibodies to Histones in Rheumatoid Arthritis","volume":"5","author":"Muzellec Y.","year":"1988","journal-title":"Diagnostic and Clinical Immunology"},{"key":"e_1_2_11_111_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202765"},{"key":"e_1_2_11_112_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0165501"},{"key":"e_1_2_11_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.04.004"},{"key":"e_1_2_11_114_1","doi-asserted-by":"publisher","DOI":"10.1093\/cei\/uxae102"},{"key":"e_1_2_11_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2012.07.011"},{"key":"e_1_2_11_116_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.74"},{"key":"e_1_2_11_117_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1017"},{"key":"e_1_2_11_118_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.56.10.613"},{"key":"e_1_2_11_119_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.7.3538"},{"key":"e_1_2_11_120_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.02.013"},{"key":"e_1_2_11_121_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35264-8"},{"key":"e_1_2_11_122_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2021.1918104"},{"key":"e_1_2_11_123_1","doi-asserted-by":"publisher","DOI":"10.1080\/14397595.2018.1532545"},{"key":"e_1_2_11_124_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67390"},{"key":"e_1_2_11_125_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00435.2010"},{"key":"e_1_2_11_126_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001620"},{"key":"e_1_2_11_127_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep26430"},{"key":"e_1_2_11_128_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2026.2657629"},{"issue":"4","key":"e_1_2_11_129_1","article-title":"Beyond PAD Inhibition: Emerging Avenues and Natural Products for Targeting Citrullination in Immune Diseases","volume":"14","author":"Chen Q.","year":"2026","journal-title":"Biomedicine"},{"key":"e_1_2_11_130_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jrn.2015.01.019"},{"key":"e_1_2_11_131_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ard.2025.06.2130"},{"key":"e_1_2_11_132_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024024362"},{"key":"e_1_2_11_133_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12970"},{"key":"e_1_2_11_134_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23361-z"}],"container-title":["Immunological Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imr.70178","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imr.70178","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imr.70178","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:09:00Z","timestamp":1790150940000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imr.70178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":133,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/imr.70178"],"URL":"https:\/\/doi.org\/10.1111\/imr.70178","archive":["Portico"],"relation":{},"ISSN":["0105-2896","1600-065X"],"issn-type":[{"value":"0105-2896","type":"print"},{"value":"1600-065X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-07-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70178"}}