{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T20:51:02Z","timestamp":1787259062388,"version":"build-2736575974"},"reference-count":95,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,6,29]],"date-time":"2019-06-29T00:00:00Z","timestamp":1561766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Post-translational modifications (PTM) are chemical changes mostly catalyzed by enzymes that recognize specific target sequences in specific proteins. These modifications play a key role in regulating the folding of proteins, their targeting to specific subcellular compartments, their interaction with ligands or other proteins, and eventually their immunogenic properties. Citrullination is the best characterized PTM in the field of rheumatology, with antibodies anticyclic citrullinated peptides being the gold standard for the diagnosis of rheumatoid arthritis (RA). In recent years, growing evidence supports not only that a wide range of proteins are subject to citrullination and can trigger an autoimmune response in RA, but also that several other PTMs such as carbamylation and acetylation occur in patients with this disease. This induces a wide spectrum of autoantibodies, as biomarkers, with different sensitivity and specificity for diagnosis, which may be linked to peculiar clinical manifestations and\/or response to treatment. The purpose of this review article is to critically summarize the available literature on antibodies against post-translationally modified proteins, in particular antibodies against citrullinated proteins (ACPA) and antibodies against modified proteins (AMPA), and outline their diagnostic and prognostic role to be implemented in clinical practice for RA patients.<\/jats:p>","DOI":"10.3390\/cells8070657","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T03:23:59Z","timestamp":1561951439000},"page":"657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Post-Translational Modifications of Proteins: Novel Insights in the Autoimmune Response in Rheumatoid Arthritis"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1958-5136","authenticated-orcid":false,"given":"Francesco","family":"Carubbi","sequence":"first","affiliation":[{"name":"Rheumatology Unit, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"},{"name":"Department of Medicine, ASL1 Avezzano-Sulmona-L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1105-5640","authenticated-orcid":false,"given":"Alessia","family":"Alunno","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Medicine, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Gerli","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Medicine, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Giacomelli","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.4081\/reumatismo.2018.1106","article-title":"Extra-articular rheumatoid arthritis","volume":"70","author":"Marcucci","year":"2018","journal-title":"Reumatismo"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"441","DOI":"10.4049\/jimmunol.63.4.441","article-title":"Serological reactions in rheumatoid arthritis; factors affecting the agglutination of sensitized sheep erythrocytes in rheumatid-arthritis serum","volume":"63","author":"Pike","year":"1949","journal-title":"J. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2174\/1573397114666180320113603","article-title":"Laboratory Assessment of Patients with Suspected Rheumatic Musculoskeletal Diseases: Challenges and Pitfalls","volume":"15","author":"Carubbi","year":"2019","journal-title":"Curr. Rheumatol. Rev."},{"key":"ref_5","first-page":"11","article-title":"Diagnostic accuracy of combined tests of anti cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis: A meta-analysis","volume":"32","author":"Sun","year":"2014","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1136\/ard.23.4.302","article-title":"A new serum factor in patients with rheumatoid arthritis; the antiperinuclear factor","volume":"23","author":"Nienhuis","year":"1964","journal-title":"Ann. Rheum. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1136\/ard.50.9.611","article-title":"Antiperinuclear factor, a marker autoantibody for rheumatoid arthritis: Colocalisation of the perinuclear factor and profilaggrin","volume":"50","author":"Hoet","year":"1991","journal-title":"Ann. Rheum. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1365-2249.1991.tb08124.x","article-title":"The perinuclear factor, a rheumatoid arthritis-specific autoantigen, is not present in keratohyalin granules of cultured buccal mucosa cells","volume":"84","author":"Hoet","year":"1991","journal-title":"Clin. Exp. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.jbspin.2012.01.008","article-title":"Citrullination under physiological and pathological conditions","volume":"79","author":"Baka","year":"2012","journal-title":"Joint Bone Spine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1007\/s11926-014-0408-9","article-title":"The link between periodontal disease and rheumatoid arthritis: An updated review","volume":"16","author":"Koziel","year":"2014","journal-title":"Curr Rheumatol Rep"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1487742","DOI":"10.1080\/20002297.2018.1487742","article-title":"Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer\u2019s disease","volume":"10","author":"Olsen","year":"2018","journal-title":"J Oral Microbiol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.chembiol.2018.03.002","article-title":"The Rheumatoid Arthritis-Associated Citrullinome","volume":"25","author":"Tilvawala","year":"2018","journal-title":"Cell. Chem. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1007\/s00296-011-1999-3","article-title":"Writing a narrative biomedical review: Considerations for authors, peer reviewers, and editors","volume":"31","author":"Gasparyan","year":"2011","journal-title":"Rheumatol. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nrrheum.2011.76","article-title":"Anti-CCP antibodies: The past, the present and the future","volume":"7","author":"Pruijn","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/ng1206","article-title":"Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis","volume":"34","author":"Suzuki","year":"2003","journal-title":"Nat Genet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.autrev.2015.01.013","article-title":"Citrullination and autoimmunity","volume":"14","author":"Valesini","year":"2015","journal-title":"Autoimmun. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1136\/ard.2010.131102","article-title":"Anti-cyclic citrullinated peptide antibodies are a collection of anti-citrullinated protein antibodies and contain overlapping and non-overlapping reactivities","volume":"70","author":"Scherer","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.4049\/jimmunol.166.6.4177","article-title":"The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the alpha- and beta-chains of fibrin","volume":"166","author":"Sebbag","year":"2001","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"178ra40","DOI":"10.1126\/scitranslmed.3005580","article-title":"NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis","volume":"5","author":"Khandpur","year":"2013","journal-title":"Sci Transl Med"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5057","DOI":"10.4049\/jimmunol.174.8.5057","article-title":"Fibrin deimination in synovial tissue is not specific for rheumatoid arthritis but commonly occurs during synovitides","volume":"174","author":"Sebbag","year":"2005","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13936","DOI":"10.1038\/srep13936","article-title":"The peptidylarginine deiminase gene is a conserved feature of Porphyromonas gingivalis","volume":"5","author":"Gabarrini","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1136\/bmj.308.6943.1552","article-title":"Statistics Notes: Diagnostic tests 1: Sensitivity and specificity","volume":"308","author":"Altman","year":"1994","journal-title":"BMJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1590\/2176-9451.19.5.027-030.ebo","article-title":"What is gold standard and what is ground truth?","volume":"19","author":"Cardoso","year":"2014","journal-title":"Dental Press J Orthod"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1172\/JCI1316","article-title":"Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies","volume":"101","author":"Schellekens","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/1529-0131(200001)43:1<155::AID-ANR20>3.0.CO;2-3","article-title":"The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide","volume":"43","author":"Schellekens","year":"2000","journal-title":"Arthritis Rheum."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s13075-015-0786-z","article-title":"An investigation of the added value of an ACPA multiplex assay in an early rheumatoid arthritis setting","volume":"17","author":"Trouw","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1002\/art.30200","article-title":"Toward a data-driven evaluation of the 2010 American College of Rheumatology\/European League Against Rheumatism criteria for rheumatoid arthritis: Is it sensible to look at levels of rheumatoid factor?","volume":"63","author":"Batstra","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1093\/rheumatology\/kex340","article-title":"The risk of individual autoantibodies, autoantibody combinations and levels for arthritis development in clinically suspect arthralgia","volume":"56","author":"Verheul","year":"2017","journal-title":"Rheumatology (Oxf.)"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/1756-185X.12040","article-title":"Comparison of anti-mutated citrullinated vimentin, anti-cyclic citrullinated peptides, anti-glucose-6-phosphate isomerase and anti-keratin antibodies and rheumatoid factor in the diagnosis of rheumatoid arthritis in Chinese patients","volume":"16","author":"Zhu","year":"2013","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/imm.12175","article-title":"Recognition of new citrulline-containing peptide epitopes by autoantibodies produced in vivo and in vitro by B cells of rheumatoid arthritis patients","volume":"141","author":"Szarka","year":"2014","journal-title":"Immunology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.bbrc.2015.07.161","article-title":"Keratin 8 is a novel autoantigen of rheumatoid arthritis","volume":"465","author":"Wang","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1002\/art.22817","article-title":"Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis","volume":"56","author":"Bang","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/art.23188","article-title":"Antibodies against citrullinated vimentin in rheumatoid arthritis: Higher sensitivity and extended prognostic value concerning future radiographic progression as compared with antibodies against cyclic citrullinated peptides","volume":"58","author":"Mathsson","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"R122","DOI":"10.1186\/ar2011","article-title":"Diagnostic value of anti-human citrullinated fibrinogen ELISA and comparison with four other anti-citrullinated protein assays","volume":"8","author":"Cantaert","year":"2006","journal-title":"Arthritis Res. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1373\/clinchem.2007.087569","article-title":"Analytical and diagnostic characteristics of 11 2nd- and 3rd-generation immunoenzymatic methods for the detection of antibodies to citrullinated proteins","volume":"53","author":"Bizzaro","year":"2007","journal-title":"Clin. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1373\/clinchem.2006.078063","article-title":"Technical and diagnostic performance of 6 assays for the measurement of citrullinated protein\/peptide antibodies in the diagnosis of rheumatoid arthritis","volume":"53","author":"Coenen","year":"2007","journal-title":"Clin. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"R119","DOI":"10.1186\/ar2008","article-title":"Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis","volume":"8","author":"Dejaco","year":"2006","journal-title":"Arthritis Res. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"491","DOI":"10.3899\/jrheum.080656","article-title":"Comparative performance analysis of 4 different anti-citrullinated protein assays in the diagnosis of rheumatoid arthritis","volume":"36","author":"Mutlu","year":"2009","journal-title":"J. Rheumatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1136\/ard.2009.108456","article-title":"Diagnostic value of anti-MCV antibodies in differentiating early inflammatory arthritis","volume":"69","author":"Damjanovska","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_41","first-page":"1002","article-title":"Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides","volume":"35","author":"Innala","year":"2008","journal-title":"J. Rheumatol."},{"key":"ref_42","first-page":"1658","article-title":"Clinical evaluation of anti-mutated citrullinated vimentin by ELISA in rheumatoid arthritis","volume":"34","author":"Szekanecz","year":"2007","journal-title":"J. Rheumatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1136\/ard.2007.071654","article-title":"Do all anti-citrullinated protein\/peptide antibody tests measure the same? Evaluation of discrepancy between anti-citrullinated protein\/peptide antibody tests in patients with and without rheumatoid arthritis","volume":"67","author":"Nogueira","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.autrev.2012.02.015","article-title":"Diagnostic value of anti-mutated citrullinated vimentin in comparison to anti-cyclic citrullinated peptide and anti-viral citrullinated peptide 2 antibodies in rheumatoid arthritis: An Italian multicentric study and review of the literature","volume":"11","author":"Bartoloni","year":"2012","journal-title":"Autoimmun. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1093\/rheumatology\/kex520","article-title":"Anti-citrullinated alpha enolase antibodies, interstitial lung disease and bone erosion in rheumatoid arthritis","volume":"57","author":"Alunno","year":"2018","journal-title":"Rheumatology (Oxf.)"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.jbspin.2017.07.009","article-title":"Anti -citrullinated peptide antibodies profiling in established rheumatoid arthritis","volume":"85","author":"Manca","year":"2018","journal-title":"Joint Bone Spine."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/cei.12677","article-title":"Comparative analysis of autoantibodies targeting peptidylarginine deiminase type 4, mutated citrullinated vimentin and cyclic citrullinated peptides in rheumatoid arthritis: Associations with cytokine profiles, clinical and genetic features","volume":"182","year":"2015","journal-title":"Clin. Exp. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/1756-185X.12544","article-title":"Diagnostic value of the anti-Sa antibody compared with the anti-cyclic citrullinated peptide antibody in rheumatoid arthritis","volume":"18","author":"Iwaszkiewicz","year":"2015","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.3899\/jrheum.111523","article-title":"Diagnostic value of anti-Sa and anticitrullinated protein antibodies in rheumatoid arthritis","volume":"39","author":"Hou","year":"2012","journal-title":"J. Rheumatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1136\/annrheumdis-2011-201056","article-title":"Autoantibodies to citrullinated fibrinogen compared with anti-MCV and anti-CCP2 antibodies in diagnosing rheumatoid arthritis at an early stage: Data from the French ESPOIR cohort","volume":"72","author":"Nogueira","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3899\/jrheum.150179","article-title":"Anti-carbamylated Protein Antibody Levels Correlate with Anti-Sa (Citrullinated Vimentin) Antibody Levels in Rheumatoid Arthritis","volume":"43","author":"Challener","year":"2016","journal-title":"J. Rheumatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1002\/art.23618","article-title":"Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis","volume":"58","author":"Kinloch","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/art.25036","article-title":"Antibodies to several citrullinated antigens are enriched in the joints of rheumatoid arthritis patients","volume":"62","author":"Snir","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1002\/art.30186","article-title":"Particular association of clinical and genetic features with autoimmunity to citrullinated \u03b1-enolase in rheumatoid arthritis","volume":"63","author":"Montes","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_55","first-page":"556","article-title":"Anti-cep-1 antibodies and other autoantibodies in early arthritis","volume":"77","author":"Ponikowska","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/cei.12033","article-title":"Anti-citrullinated glucose-6-phosphate isomerase peptide antibodies in patients with rheumatoid arthritis are associated with HLA-DRB1 shared epitope alleles and disease activity","volume":"172","author":"Umeda","year":"2013","journal-title":"Clin. Exp. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1002\/eji.200535790","article-title":"Epitopes of human fibrin recognized by the rheumatoid arthritis-specific autoantibodies to citrullinated proteins","volume":"36","author":"Sebbag","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/ar537","article-title":"Autoantibodies to deiminated fibrinogen are the most efficient serological criterion for the diagnosis of rheumatoid arthritis","volume":"4","author":"Nogueira","year":"2002","journal-title":"Arthritis Res. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1136\/annrheumdis-2012-202868","article-title":"The fibrin-derived citrullinated peptide \u03b260-74Cit60,72,74 bears the major ACPA epitope recognised by the rheumatoid arthritis-specific anticitrullinated fibrinogen autoantibodies and anti-CCP2 antibodies","volume":"73","author":"Cornillet","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.clim.2014.02.011","article-title":"In Black Africans with rheumatoid arthritis, ACPA recognize citrullinated fibrinogen and the derived peptides \u03b136-50Cit38,42 and \u03b260-74Cit60,72,74, like in Caucasians","volume":"152","author":"Nogueira","year":"2014","journal-title":"Clin. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13075-014-0515-z","article-title":"Separate and overlapping specificities in rheumatoid arthritis antibodies binding to citrulline- and homocitrulline-containing peptides related to type I and II collagen telopeptides","volume":"17","author":"Turunen","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1136\/annrheumdis-2011-200848","article-title":"Antibodies binding to citrullinated telopeptides of type I and type II collagens and to mutated citrullinated vimentin synergistically predict the development of seropositive rheumatoid arthritis","volume":"71","author":"Koivula","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1002\/art.22983","article-title":"Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation","volume":"56","author":"Foulquier","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1136\/ard.2007.080267","article-title":"Serum IgG antibodies to peptidylarginine deiminase 4 in rheumatoid arthritis and associations with disease severity","volume":"67","author":"Halvorsen","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"794","DOI":"10.3109\/s10165-012-0748-0","article-title":"Two novel sandwich ELISAs identify PAD4 levels and PAD4 autoantibodies in patients with rheumatoid arthritis","volume":"23","author":"Ishigami","year":"2013","journal-title":"Mod. Rheumatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.3899\/jrheum.130293","article-title":"Prevalence of anti-peptidylarginine deiminase type 4 antibodies in rheumatoid arthritis and unaffected first-degree relatives in indigenous North American Populations","volume":"40","author":"Ferucci","year":"2013","journal-title":"J. Rheumatol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Giles, J.T., Darrah, E., Danoff, S., Johnson, C., Andrade, F., Rosen, A., and Bathon, J.M. (2014). Association of cross-reactive antibodies targeting peptidyl-arginine deiminase 3 and 4 with rheumatoid arthritis-associated interstitial lung disease. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098794"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"186ra65","DOI":"10.1126\/scitranslmed.3005370","article-title":"Erosive rheumatoid arthritis is associated with antibodies that activate PAD4 by increasing calcium sensitivity","volume":"5","author":"Darrah","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/0167-5699(93)90244-F","article-title":"Defining criteria for autoimmune diseases (Witebsky\u2019s postulates revisited)","volume":"14","author":"Rose","year":"1993","journal-title":"Immunol Today"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1136\/annrheumdis-2019-215337","article-title":"Pathogenic effector functions of ACPA: Where do we stand?","volume":"78","author":"Toes","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"728610","DOI":"10.1155\/2015\/728610","article-title":"The role of citrullinated protein antibodies in predicting erosive disease in rheumatoid arthritis: A systematic literature review and meta-analysis","volume":"2015","author":"Jilani","year":"2015","journal-title":"Int. J. Rheumatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e000009","DOI":"10.1136\/rmdopen-2014-000009","article-title":"Therapeutic implications of autoantibodies in rheumatoid arthritis","volume":"2","author":"Aletaha","year":"2016","journal-title":"RMD Open"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.clim.2019.01.001","article-title":"High levels of antibodies to citrullinated \u03b1-enolase peptide-1 (CEP-1) identify erosions and interstitial lung disease (ILD) in a Chinese rheumatoid arthritis cohort","volume":"200","author":"Liu","year":"2019","journal-title":"Clin. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1136\/ard.2010.138909","article-title":"Antibodies to citrullinated \u03b1-enolase peptide 1 and clinical and radiological outcomes in rheumatoid arthritis","volume":"70","author":"Fisher","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1002\/art.23596","article-title":"Association of autoimmunity to peptidyl arginine deiminase type 4 with genotype and disease severity in rheumatoid arthritis","volume":"58","author":"Harris","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1002\/art.27570","article-title":"Autoimmunity to peptidyl arginine deiminase type 4 precedes clinical onset of rheumatoid arthritis","volume":"62","author":"Kolfenbach","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1136\/ard.2008.094490","article-title":"Serum IgG antibodies to peptidylarginine deiminase 4 predict radiographic progression in patients with rheumatoid arthritis treated with tumour necrosis factor-alpha blocking agents","volume":"68","author":"Halvorsen","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1097\/BOR.0000000000000270","article-title":"Management of connective tissue diseases associated interstitial lung disease: A review of the published literature","volume":"28","author":"Wallace","year":"2016","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7915340","DOI":"10.1155\/2017\/7915340","article-title":"Clinical, Epidemiological, and Histopathological Features of Respiratory Involvement in Rheumatoid Arthritis","volume":"2017","author":"Alunno","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.3899\/jrheum.150166","article-title":"A Study of Multiple Causes of Death in Rheumatoid Arthritis","volume":"42","author":"Pinheiro","year":"2015","journal-title":"J. Rheumatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/art.1780150311","article-title":"Rheumatoid factor accentuation of pulmonary lesions associated with experimental diffuse proliferative lung disease","volume":"15","author":"DeHoratius","year":"1972","journal-title":"Arthritis Rheum."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1093\/rheumatology\/keu165","article-title":"Rheumatoid arthritis-related interstitial lung disease: Associations, prognostic factors and physiological and radiological characteristics--a large multicentre UK study","volume":"53","author":"Kelly","year":"2014","journal-title":"Rheumatology (Oxf.)"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1136\/annrheumdis-2013-203510","article-title":"Antibodies to modified citrullinated vimentin are associated with severe extra-articular manifestations in rheumatoid arthritis","volume":"72","author":"Turesson","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_84","first-page":"536050","article-title":"Anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti-MCV) relation with extra-articular manifestations in rheumatoid arthritis","volume":"2014","author":"Nava","year":"2014","journal-title":"J. Immunol. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3389\/fimmu.2015.00192","article-title":"Citrullination and carbamylation in the pathophysiology of rheumatoid arthritis","volume":"6","author":"Pruijn","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1038\/nm1637","article-title":"Protein carbamylation links inflammation, smoking, uremia and atherogenesis","volume":"13","author":"Wang","year":"2007","journal-title":"Nat. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.autrev.2013.10.008","article-title":"Carbamylation and antibodies against carbamylated proteins in autoimmunity and other pathologies","volume":"13","author":"Shi","year":"2014","journal-title":"Autoimmun. Rev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1136\/annrheumdis-2016-210059","article-title":"Carbamylation of vimentin is inducible by smoking and represents an independent autoantigen in rheumatoid arthritis","volume":"76","author":"Ospelt","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1002\/art.40562","article-title":"Triple Positivity for Anti-Citrullinated Protein Autoantibodies, Rheumatoid Factor, and Anti-Carbamylated Protein Antibodies Conferring High Specificity for Rheumatoid Arthritis: Implications for Very Early Identification of At-Risk Individuals","volume":"70","author":"Verheul","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13075-015-0536-2","article-title":"Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis, their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage","volume":"17","author":"Brink","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"572","DOI":"10.3899\/jrheum.140767","article-title":"Anti-carbamylated protein antibodies are present prior to rheumatoid arthritis and are associated with its future diagnosis","volume":"42","author":"Gan","year":"2015","journal-title":"J. Rheumatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1186\/s13075-015-0860-6","article-title":"The specificity of anti-carbamylated protein antibodies for rheumatoid arthritis in a setting of early arthritis","volume":"17","author":"Shi","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1136\/annrheumdis-2015-207326","article-title":"Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis: Results from the Norfolk Arthritis Register","volume":"75","author":"Humphreys","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1136\/ard.2003.014233","article-title":"Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: Role of antibodies to citrullinated peptides (anti-CCP)","volume":"63","author":"Forslind","year":"2004","journal-title":"Ann. Rheum. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1136\/annrheumdis-2014-206785","article-title":"Identification of novel antiacetylated vimentin antibodies in patients with early inflammatory arthritis","volume":"75","author":"Juarez","year":"2016","journal-title":"Ann. Rheum. 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