{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:32:24Z","timestamp":1791322344639,"version":"4.3.1"},"reference-count":73,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T00:00:00Z","timestamp":1471392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Conversion of arginine into citrulline is a post\u2010translational modification that is observed in normal physiological processes. However, abnormal citrullination can provoke autoimmunity by generating altered self\u2010epitopes that are specifically targeted by autoantibodies and T cells. In this review we discuss the recognition of citrullinated antigens in human autoimmune diseases and the role that this modification plays in increasing antigenic diversity and circumventing tolerance mechanisms. Early published work demonstrated that citrullinated proteins are specifically targeted by autoantibodies in rheumatoid arthritis and that citrullinated peptides are more readily presented to T cells by arthritis\u2010susceptible HLA class II \u2018shared epitope\u2019 proteins. Emerging data support the relevance of citrullinated epitopes in other autoimmune diseases, including type 1 diabetes and multiple sclerosis, whose susceptible HLA haplotypes also preferentially present citrullinated peptides. In these settings, autoimmune patients have been shown to have elevated responses to citrullinated epitopes derived from tissue\u2010specific antigens. Contrasting evidence implicates autophagy or perforin and complement\u2010mediated membrane attack as inducers of ectopic citrullination. In either case, the peptidyl deiminases responsible for citrullination are activated in response to inflammation or insult, providing a mechanistic link between this post\u2010translational modification and interactions with the environment and infection. As such, it is likely that immune recognition of citrullinated epitopes also plays a role in pathogen clearance. Indeed, our recent data suggest that responses to citrullinated peptides facilitate recognition of novel influenza strains. Therefore, increased understanding of responses to citrullinated epitopes may provide important insights about the initiation of autoimmunity and recognition of heterologous viruses.<\/jats:p>","DOI":"10.1111\/imm.12640","type":"journal-article","created":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T07:53:26Z","timestamp":1467186806000},"page":"131-138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Immune recognition of citrullinated epitopes"],"prefix":"10.1111","volume":"149","author":[{"given":"Hai","family":"Nguyen","sequence":"first","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie A.","family":"James","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/207691"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2011.12.003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2006.03.008"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.12.013"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131241"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.2.538"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072051"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27594"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar95"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.4.110807.092254"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2011.01.014"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.23.4.302"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.6182.97"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10436"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-007-8022-5"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23936"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526000"},{"key":"e_1_2_9_19_1","first-page":"2115","article-title":"Serum autoantibodies that bind citrullinated fibrinogen are frequently found in patients with rheumatoid arthritis","volume":"33","author":"Hill JA","year":"2006","journal-title":"J Rheumatol"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30537"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3840"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20018"},{"key":"e_1_2_9_23_1","first-page":"383","article-title":"Anticitrullinated protein\/peptide antibody and its role in the diagnosis and prognosis of early rheumatoid arthritis","volume":"60","author":"Venrooij WJ","year":"2002","journal-title":"Neth J Med"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11223"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780301102"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2462"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.25059"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30445"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.25064"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3848"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-201234.5"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39553"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201517"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38637"},{"key":"e_1_2_9_35_1","first-page":"1534","article-title":"Diabetes\u2010associated autoantibodies in relation to clinical characteristics and natural course in children with newly diagnosed type 1 diabetes. The Childhood Diabetes In Finland Study Group","volume":"84","author":"Sabbah E","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05911"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.1993.tb00616.x"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051251"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0112"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1214"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1952"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0621"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117300"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400106"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20316"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21329"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.1.123"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1177\/135245850000600402"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(01)00312-5"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200806072"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203844"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-247254"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33432"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3707"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202765"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.3.1421"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2012.01.008"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10357"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb1961.50.2899"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.44.27893"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2004.12.005"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.1391"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.075192"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.4848.1231"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.091398"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e32835fb8ec"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.42.7"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2010.01271.x"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0039"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652406775574613"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110640"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11229"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006869"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1021\/ml300288d"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimm.12640","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.12640","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T16:15:02Z","timestamp":1696176902000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.12640"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,17]]},"references-count":73,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1111\/imm.12640"],"URL":"https:\/\/doi.org\/10.1111\/imm.12640","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,17]]},"assertion":[{"value":"2016-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-06-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}