{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:36:24Z","timestamp":1792445784250,"version":"4.5.0"},"reference-count":186,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Collagen type II (COL2), the main structural protein of hyaline cartilage, is considerably affected by autoimmune responses associated with the pathogenesis of rheumatoid arthritis (RA). Posttranslational modifications (PTMs) play a significant role in the formation of the COL2 molecule and supramolecular fibril organization, and thus, support COL2 function, which is crucial for normal cartilage structure and physiology. Conversely, the specific PTMs of the protein (carbamylation, glycosylation, citrullination, oxidative modifications and others) have been implicated in RA autoimmunity. The discovery of the anti-citrullinated protein response in RA, which includes anti-citrullinated COL2 reactivity, has led to the development of improved diagnostic assays and classification criteria for the disease. The induction of immunological tolerance using modified COL2 peptides has been highlighted as a potentially effective strategy for RA therapy. Therefore, the aim of this review is to summarize the recent knowledge on COL2 posttranslational modifications with relevance to RA pathophysiology, diagnosis and treatment. The significance of COL2 PTMs as a source of neo-antigens that activate immunity leading to or sustaining RA autoimmunity is discussed.<\/jats:p>","DOI":"10.3390\/ijms24129884","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T03:29:48Z","timestamp":1686194988000},"page":"9884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Significance of Type II Collagen Posttranslational Modifications: From Autoantigenesis to Improved Diagnosis and Treatment of Rheumatoid Arthritis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-1945","authenticated-orcid":false,"given":"Tsvetelina","family":"Batsalova","sequence":"first","affiliation":[{"name":"Faculty of Biology, Paisii Hilendarski University of Plovdiv, 24 Tsar Assen Str., 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8052-5840","authenticated-orcid":false,"given":"Balik","family":"Dzhambazov","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Paisii Hilendarski University of Plovdiv, 24 Tsar Assen Str., 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102400","DOI":"10.1016\/j.jaut.2019.102400","article-title":"The etiology of rheumatoid arthritis","volume":"110","author":"Scherer","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41413-018-0016-9","article-title":"Rheumatoid arthritis: Pathological mechanisms and modern pharmacologic therapies","volume":"6","author":"Guo","year":"2018","journal-title":"Bone Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102776","DOI":"10.1016\/j.autrev.2021.102776","article-title":"Rheumatoid arthritis: Extra-articular manifestations and comorbidities","volume":"20","author":"Figus","year":"2021","journal-title":"Autoimmun. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/j.clinthera.2019.04.028","article-title":"The Natural History of Rheumatoid Arthritis","volume":"41","author":"Deane","year":"2019","journal-title":"Clin. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jcyt.2021.10.003","article-title":"Rheumatoid arthritis: From synovium biology to cell-based therapy","volume":"24","author":"Debreova","year":"2022","journal-title":"Cytotherapy"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.jfma.2022.01.026","article-title":"Tissue microenvironment dictates inflammation and disease activity in rheumatoid arthritis","volume":"121","author":"Cheng","year":"2022","journal-title":"J. Formos. Med. Assoc. Taiwan Yi Zhi"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mueller, A.L., Payandeh, Z., Mohammadkhani, N., Mubarak, S.M.H., Zakeri, A., Alagheband Bahrami, A., Brockmueller, A., and Shakibaei, M. (2021). Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies. Cells, 10.","DOI":"10.3390\/cells10113017"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41590-020-00816-x","article-title":"The immunology of rheumatoid arthritis","volume":"22","author":"Weyand","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.gene.2019.03.033","article-title":"Genetic implications in the pathogenesis of rheumatoid arthritis; an updated review","volume":"702","author":"Karami","year":"2019","journal-title":"Gene"},{"key":"ref_10","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. Prim."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"680043","DOI":"10.3389\/fphar.2021.680043","article-title":"The Therapeutic Landscape of Rheumatoid Arthritis: Current State and Future Directions","volume":"12","author":"Shams","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"834247","DOI":"10.3389\/fimmu.2022.834247","article-title":"New Druggable Targets for Rheumatoid Arthritis Based on Insights from Synovial Biology","volume":"13","author":"Sandhu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E712","DOI":"10.1016\/S2665-9913(20)30344-1","article-title":"Autoantigens in rheumatoid arthritis and the potential for antigen-specific tolerising immunotherapy","volume":"2","author":"Nel","year":"2020","journal-title":"Lancet Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Poulsen, T.B.G., Damgaard, D., Jorgensen, M.M., Senolt, L., Blackburn, J.M., Nielsen, C.H., and Stensballe, A. (2020). Identification of Novel Native Autoantigens in Rheumatoid Arthritis. Biomedicines, 8.","DOI":"10.3390\/biomedicines8060141"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.immuni.2017.02.006","article-title":"Immunopathogenesis of Rheumatoid Arthritis","volume":"46","author":"Firestein","year":"2017","journal-title":"Immunity"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s12016-021-08890-1","article-title":"Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings","volume":"63","author":"Sokolova","year":"2022","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.bbrc.2006.08.105","article-title":"Patients with inflammatory arthritic diseases harbor elevated serum and synovial fluid levels of free and immune-complexed glucose-6-phosphate isomerase (G6PI)","volume":"349","author":"Schaller","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1136\/annrheumdis-2015-208529","article-title":"Antibodies to native and citrullinated RA33 (hnRNP A2\/B1) challenge citrullination as the inciting principle underlying loss of tolerance in rheumatoid arthritis","volume":"75","author":"Konig","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.4049\/jimmunol.169.2.1068","article-title":"Characterization of autoreactive T cells to the autoantigens heterogeneous nuclear ribonucleoprotein A2 (RA33) and filaggrin in patients with rheumatoid arthritis","volume":"169","author":"Fritsch","year":"2002","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrrheum.2015.43","article-title":"Immunology: BiP peptides induce epitope-specific T-cell reactions in RA","volume":"11","author":"Onuora","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3389\/fimmu.2016.00485","article-title":"NETosis as Source of Autoantigens in Rheumatoid Arthritis","volume":"7","author":"Corsiero","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1186\/ar95","article-title":"Citrullination: A small change for a protein with great consequences for rheumatoid arthritis","volume":"2","author":"Pruijn","year":"2000","journal-title":"Arthritis Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"145217","DOI":"10.1172\/jci.insight.145217","article-title":"Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis","volume":"6","author":"Song","year":"2021","journal-title":"JCI Insight"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1136\/annrheumdis-2016-210873","article-title":"Anticollagen type II antibodies are associated with an acute onset rheumatoid arthritis phenotype and prognosticate lower degree of inflammation during 5 years follow-up","volume":"76","author":"Manivel","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Whittingham, S.F., Stockman, A., and Rowley, M.J. (2017). Collagen Autoantibodies and Their Relationship to CCP Antibodies and Rheumatoid Factor in the Progression of Early Rheumatoid Arthritis. Antibodies, 6.","DOI":"10.3390\/antib6020006"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/00000441-200404000-00006","article-title":"Type II collagen autoimmunity in rheumatoid arthritis","volume":"327","author":"Kim","year":"2004","journal-title":"Am. J. Med. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"C1061","DOI":"10.1152\/ajpcell.00086.2022","article-title":"Emerging proteoglycans and proteoglycan-targeted therapies in rheumatoid arthritis","volume":"322","author":"Hurysz","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1093\/rheumatology\/keg230","article-title":"Predominant cellular immune response to the cartilage autoantigenic G1 aggrecan in ankylosing spondylitis and rheumatoid arthritis","volume":"42","author":"Zou","year":"2003","journal-title":"Rheumatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3731","DOI":"10.7150\/ijbs.67587","article-title":"The role of YKL-40 in the pathogenesis of autoimmune diseases: A comprehensive review","volume":"18","author":"Tizaoui","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1002\/art.42072","article-title":"Antibodies to Cartilage Oligomeric Matrix Protein Are Pathogenic in Mice and May Be Clinically Relevant in Rheumatoid Arthritis","volume":"74","author":"Ge","year":"2022","journal-title":"Arthritis Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/283666a0","article-title":"Immunisation against heterologous type II collagen induces arthritis in mice","volume":"283","author":"Courtenay","year":"1980","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00281-003-0127-1","article-title":"Immunopathogenesis of collagen arthritis","volume":"25","author":"Brand","year":"2003","journal-title":"Springer Semin. Immunopathol."},{"key":"ref_33","first-page":"575","article-title":"IgG antibodies to type II collagen reflect inflammatory activity in patients with rheumatoid arthritis","volume":"27","author":"Kim","year":"2000","journal-title":"J. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00441-009-0816-8","article-title":"Pathogenic antibody recognition of cartilage","volume":"339","author":"Nandakumar","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13075-015-0523-7","article-title":"Anti-type II collagen immune complex-induced granulocyte reactivity is associated with joint erosions in RA patients with anti-collagen antibodies","volume":"17","author":"Manivel","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1016\/j.ebiom.2015.11.019","article-title":"Collagen Specific T-Cell Repertoire and HLA-DR Alleles: Biomarkers of Active Refractory Rheumatoid Arthritis","volume":"2","author":"Tolusso","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1002\/art.34459","article-title":"Multifunctional T cell reactivity with native and glycosylated type II collagen in rheumatoid arthritis","volume":"64","author":"Snir","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9960","DOI":"10.1073\/pnas.132254199","article-title":"Predominant selection of T cells specific for the glycosylated collagen type II epitope (263\u2013270) in humanized transgenic mice and in rheumatoid arthritis","volume":"99","author":"Backlund","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1136\/ard.58.7.446","article-title":"Type II collagen is a target antigen of clonally expanded T cells in the synovium of patients with rheumatoid arthritis","volume":"58","author":"Sekine","year":"1999","journal-title":"Ann. Rheum. Dis."},{"key":"ref_40","first-page":"225","article-title":"T cell proliferative response to type II collagen in the inflammatory process and joint damage in patients with rheumatoid arthritis","volume":"32","author":"Kim","year":"2005","journal-title":"J. Rheumatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.4049\/jimmunol.176.3.1525","article-title":"Therapeutic vaccination of active arthritis with a glycosylated collagen type II peptide in complex with MHC class II molecules","volume":"176","author":"Dzhambazov","year":"2006","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"112294","DOI":"10.1016\/j.biopha.2021.112294","article-title":"Different protective efficacies of a novel antigen-specific DNA vaccine encoding chicken type II collagen via intramuscular, subcutaneous, and intravenous vaccination against experimental rheumatoid arthritis","volume":"144","author":"Zhao","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hou, C., Li, N., Liu, M., Chen, J., Elango, J., Rahman, S.U., Bao, B., and Wu, W. (2022). Therapeutic Effect of Nile Tilapia Type II Collagen on Rigidity in CD8+ Cells by Alleviating Inflammation and Rheumatoid Arthritis in Rats by Oral Tolerance. Polymers, 14.","DOI":"10.3390\/polym14071284"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/nature16962","article-title":"Expanding antigen-specific regulatory networks to treat autoimmunity","volume":"530","author":"Blanco","year":"2016","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"R180","DOI":"10.1186\/ar2870","article-title":"A multicenter, double-blind, randomized, controlled phase III clinical trial of chicken type II collagen in rheumatoid arthritis","volume":"11","author":"Wei","year":"2009","journal-title":"Arthritis Res. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1126\/science.8378772","article-title":"Effects of oral administration of type II collagen on rheumatoid arthritis","volume":"261","author":"Trentham","year":"1993","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/1529-0131(199802)41:2<290::AID-ART13>3.0.CO;2-R","article-title":"Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial","volume":"41","author":"Barnett","year":"1998","journal-title":"Arthritis Rheum."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2015.11.001","article-title":"Extracellular matrix structure","volume":"97","author":"Theocharis","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nrm3902","article-title":"Extracellular matrix assembly: A multiscale deconstruction","volume":"15","author":"Mouw","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1242\/jcs.03453","article-title":"Collagens at a glance","volume":"120","author":"Kadler","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1146\/annurev-cellbio-092910-154013","article-title":"Transmembrane collagen receptors","volume":"27","author":"Leitinger","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.tig.2003.11.004","article-title":"Collagens, modifying enzymes and their mutations in humans, flies and worms","volume":"20","author":"Myllyharju","year":"2004","journal-title":"Trends Genet. TIG"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1146\/annurev.biochem.77.032207.120833","article-title":"Collagen structure and stability","volume":"78","author":"Shoulders","year":"2009","journal-title":"Annu. Rev. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1042\/bse0520113","article-title":"Lysine post-translational modifications of collagen","volume":"52","author":"Yamauchi","year":"2012","journal-title":"Essays Biochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7342","DOI":"10.1002\/anie.200501023","article-title":"Protein posttranslational modifications: The chemistry of proteome diversifications","volume":"44","author":"Walsh","year":"2005","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/srep00090","article-title":"Proteome-wide post-translational modification statistics: Frequency analysis and curation of the swiss-prot database","volume":"1","author":"Khoury","year":"2011","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s00726-019-02747-w","article-title":"Investigation of the impact of PTMs on the protein backbone conformation","volume":"51","author":"Craveur","year":"2019","journal-title":"Amino Acids"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1196\/annals.1313.001","article-title":"Posttranslational modifications of self-antigens","volume":"1050","author":"Doyle","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1093\/rheumatology\/ken014","article-title":"Consequence of neo-antigenicity of the \u2018altered self\u2019","volume":"47","author":"Eggleton","year":"2008","journal-title":"Rheumatology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.coi.2004.09.001","article-title":"Post-translational modifications of self antigens: Implications for autoimmunity","volume":"16","author":"Anderton","year":"2004","journal-title":"Curr. Opin. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Kwon, E.J., and Ju, J.H. (2021). Impact of Posttranslational Modification in Pathogenesis of Rheumatoid Arthritis: Focusing on Citrullination, Carbamylation, and Acetylation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910576"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Becart, S., Whittington, K.B., Prislovsky, A., Rao, N.L., and Rosloniec, E.F. (2021). The role of posttranslational modifications in generating neo-epitopes that bind to rheumatoid arthritis-associated HLA-DR alleles and promote autoimmune T cell responses. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0245541"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1001\/jama.2018.13103","article-title":"Diagnosis and Management of Rheumatoid Arthritis: A Review","volume":"320","author":"Aletaha","year":"2018","journal-title":"JAMA"},{"key":"ref_64","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_65","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nrrheum.2017.15","article-title":"Beyond citrullination: Other post-translational protein modifications in rheumatoid arthritis","volume":"13","author":"Trouw","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/art.40699","article-title":"Recognition of Amino Acid Motifs, Rather Than Specific Proteins, by Human Plasma Cell-Derived Monoclonal Antibodies to Posttranslationally Modified Proteins in Rheumatoid Arthritis","volume":"71","author":"Steen","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Moten, D., Teneva, I., Apostolova, D., Batsalova, T., and Dzhambazov, B. (2022). Molecular Mimicry of the Rheumatoid Arthritis-Related Immunodominant T-Cell Epitope within Type II Collagen (CII260-270) by the Bacterial L-Asparaginase. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169149"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/s41467-017-02763-y","article-title":"T cells specific for post-translational modifications escape intrathymic tolerance induction","volume":"9","author":"Raposo","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1002\/(SICI)1521-4141(199808)28:08<2580::AID-IMMU2580>3.0.CO;2-X","article-title":"Epitope glycosylation plays a critical role for T cell recognition of type II collagen in collagen-induced arthritis","volume":"28","author":"Corthay","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"ref_70","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_71","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jbspin.2015.10.003","article-title":"New autoantibodies associated with rheumatoid arthritis recognize posttranslationally modified self-proteins","volume":"83","author":"Cantagrel","year":"2016","journal-title":"Jt. Bone Spine"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/eji.200425637","article-title":"The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans","volume":"35","author":"Dzhambazov","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0076-6879(82)82067-3","article-title":"Posttranslational enzymes in the biosynthesis of collagen: Intracellular enzymes","volume":"82 Pt A","author":"Kivirikko","year":"1982","journal-title":"Methods Enzymol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1080\/10409238.2016.1269716","article-title":"Molecular insights into prolyl and lysyl hydroxylation of fibrillar collagens in health and disease","volume":"52","author":"Gjaltema","year":"2017","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1046\/j.1432-1033.2002.02784.x","article-title":"Interaction of decorin with CNBr peptides from collagens I and II. Evidence for multiple binding sites and essential lysyl residues in collagen","volume":"269","author":"Tenni","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5480","DOI":"10.18632\/oncotarget.23869","article-title":"Decorin is a pivotal effector in the extracellular matrix and tumour microenvironment","volume":"9","author":"Zhang","year":"2018","journal-title":"Oncotarget"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8988","DOI":"10.1074\/jbc.274.13.8988","article-title":"Recombinant human type II collagens with low and high levels of hydroxylysine and its glycosylated forms show marked differences in fibrillogenesis in vitro","volume":"274","author":"Notbohm","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.4049\/jimmunol.172.5.2970","article-title":"Relevance of posttranslational modifications for the arthritogenicity of type II collagen","volume":"172","author":"Myers","year":"2004","journal-title":"J. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4729","DOI":"10.4049\/jimmunol.173.7.4729","article-title":"A transient post-translationally modified form of cartilage type II collagen is ignored by self-reactive T cells","volume":"173","author":"Yamada","year":"2004","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1084\/jem.180.2.745","article-title":"T cell recognition of carbohydrates on type II collagen","volume":"180","author":"Michaelsson","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1002\/eji.1830220722","article-title":"Identification of an immunodominant type-II collagen peptide recognized by T cells in H-2q mice: Self tolerance at the level of determinant selection","volume":"22","author":"Michaelsson","year":"1992","journal-title":"Eur. J. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"253","DOI":"10.4049\/jimmunol.168.1.253","article-title":"HLA-DR1 (DRB1*0101) and DR4 (DRB1*0401) use the same anchor residues for binding an immunodominant peptide derived from human type II collagen","volume":"168","author":"Rosloniec","year":"2002","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s002510050461","article-title":"Human collagen II peptide 256-271 preferentially binds to HLA-DR molecules associated with susceptibility to rheumatoid arthritis","volume":"49","author":"Diab","year":"1999","journal-title":"Immunogenetics"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/eji.1830260431","article-title":"Specificity of an HLA-DRB1*0401-restricted T cell response to type II collagen","volume":"26","author":"Fugger","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7574","DOI":"10.1073\/pnas.95.13.7574","article-title":"Definition of MHC and T cell receptor contacts in the HLA-DR4 restricted immunodominant epitope in type II collagen and characterization of collagen-induced arthritis in HLA-DR4 and human CD4 transgenic mice","volume":"95","author":"Andersson","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","first-page":"331","article-title":"T cell epitopes of type II collagen in HLA-DRB1*0101 or DRB1*0405-positive Japanese patients with rheumatoid arthritis","volume":"11","author":"Ohnishi","year":"2003","journal-title":"Int. J. Mol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1002\/1529-0131(199910)42:10<2085::AID-ANR8>3.0.CO;2-Z","article-title":"Enhanced T cell proliferative response to type II collagen and synthetic peptide CII (255\u2013274) in patients with rheumatoid arthritis","volume":"42","author":"Kim","year":"1999","journal-title":"Arthritis Rheum."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1002\/art.27460","article-title":"Breaking T cell tolerance against self type II collagen in HLA-DR4-transgenic mice and development of autoimmune arthritis","volume":"62","author":"Batsalova","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1136\/annrheumdis-2021-220500","article-title":"Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide and the T-cell receptor","volume":"81","author":"Ge","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1093\/glycob\/cww062","article-title":"Carbohydrates as T-cell antigens with implications in health and disease","volume":"26","author":"Sun","year":"2016","journal-title":"Glycobiology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"700","DOI":"10.2174\/1389450116666150202160954","article-title":"Protein Arginine Deiminases and Associated Citrullination: Physiological Functions and Diseases Associated with Dysregulation","volume":"16","author":"Witalison","year":"2015","journal-title":"Curr. Drug Targets"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"109134","DOI":"10.1016\/j.clim.2022.109134","article-title":"Citrullination: A modification important in the pathogenesis of autoimmune diseases","volume":"245","author":"Zhu","year":"2022","journal-title":"Clin. Immunol."},{"key":"ref_93","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_94","doi-asserted-by":"crossref","first-page":"7592851","DOI":"10.1155\/2019\/7592851","article-title":"An Overview of the Intrinsic Role of Citrullination in Autoimmune Disorders","volume":"2019","author":"Alghamdi","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"102392","DOI":"10.1016\/j.jaut.2019.102392","article-title":"An overview of autoantibodies in rheumatoid arthritis","volume":"110","author":"Huizinga","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/nrrheum.2011.204","article-title":"The influence of ACPA status and characteristics on the course of RA","volume":"8","author":"Willemze","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00296-010-1671-3","article-title":"Anti-cyclic citrullinated peptide antibody predicts functional disability in patients with rheumatoid arthritis in a large prospective observational cohort in Japan","volume":"32","author":"Shidara","year":"2012","journal-title":"Rheumatol. Int."},{"key":"ref_98","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_99","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/art.39827","article-title":"Differences in the Spectrum of Anti-Citrullinated Protein Antibody Fine Specificities between Malaysian and Swedish Patients with Rheumatoid Arthritis: Implications for Disease Pathogenesis","volume":"69","author":"Too","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e93688","DOI":"10.1172\/jci.insight.93688","article-title":"Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage","volume":"2","author":"Ge","year":"2017","journal-title":"JCI Insight"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s13075-022-02945-0","article-title":"Rheumatoid arthritis sera antibodies to citrullinated collagen type II bind to joint cartilage","volume":"24","author":"Li","year":"2022","journal-title":"Arthritis Res. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1093\/rheumatology\/kez073","article-title":"The autoantibody response to cyclic citrullinated collagen type II peptides in rheumatoid arthritis","volume":"58","author":"Liang","year":"2019","journal-title":"Rheumatology"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Carubbi, F., Alunno, A., Gerli, R., and Giacomelli, R. (2019). Post-Translational Modifications of Proteins: Novel Insights in the Autoimmune Response in Rheumatoid Arthritis. Cells, 8.","DOI":"10.3390\/cells8070657"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"692242","DOI":"10.3389\/fimmu.2021.692242","article-title":"Pathogenic Role of Circulating Citrullinated Antigens and Anti-Cyclic Monoclonal Citrullinated Peptide Antibodies in Rheumatoid Arthritis","volume":"12","author":"Won","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1084\/jem.20081862","article-title":"Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis","volume":"206","author":"Uysal","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1002\/art.38383","article-title":"Identification of new citrulline-specific autoantibodies, which bind to human arthritic cartilage, by mass spectrometric analysis of citrullinated type II collagen","volume":"66","author":"Haag","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s12026-013-8479-7","article-title":"Induction of bone loss in DBA\/1J mice immunized with citrullinated autologous mouse type II collagen in the absence of adjuvant","volume":"58","author":"Dusad","year":"2014","journal-title":"Immunol. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.intimp.2012.05.007","article-title":"Citrullinated mouse collagen administered to DBA\/1J mice in the absence of adjuvant initiates arthritis","volume":"13","author":"Thiele","year":"2012","journal-title":"Int. Immunopharmacol."},{"key":"ref_109","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_110","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_111","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_112","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_113","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1136\/ard.2008.091355","article-title":"Multiple antibody reactivities to citrullinated antigens in sera from patients with rheumatoid arthritis: Association with HLA-DRB1 alleles","volume":"68","author":"Snir","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/cei.12825","article-title":"Effects of type II collagen epitope carbamylation and citrullination in human leucocyte antigen (HLA)-DR4+ monozygotic twins discordant for rheumatoid arthritis","volume":"185","author":"Ceribelli","year":"2016","journal-title":"Clin. Exp. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/art.40698","article-title":"Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies","volume":"71","author":"Ge","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1096\/fj.13-247767","article-title":"Citrullination of collagen II affects integrin-mediated cell adhesion in a receptor-specific manner","volume":"28","author":"Sipila","year":"2014","journal-title":"FASEB J."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Myers, L.K., Ouyang, Y.X., Patel, J.R., Odens, H.H., Woo-Rasberry, V., Park, J., Yi, A.K., Rosloniec, E.F., Brand, D.D., and Stuart, J.M. (2022). Role of Citrullinated Collagen in Autoimmune Arthritis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179833"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.3389\/fimmu.2020.01793","article-title":"Leukocyte Associated Immunoglobulin Like Receptor 1 Regulation and Function on Monocytes and Dendritic Cells During Inflammation","volume":"11","author":"Carvalheiro","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_119","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_120","doi-asserted-by":"crossref","unstructured":"Ishina, I.A., Zakharova, M.Y., Kurbatskaia, I.N., Mamedov, A.E., Belogurov, A.A., and Gabibov, A.G. (2023). MHC Class II Presentation in Autoimmunity. Cells, 12.","DOI":"10.3390\/cells12020314"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Sidney, J., Becart, S., Zhou, M., Duffy, K., Lindvall, M., Moore, E.C., Moore, E.L., Rao, T., Rao, N., and Nielsen, M. (2017). Citrullination only infrequently impacts peptide binding to HLA class II MHC. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177140"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"538","DOI":"10.4049\/jimmunol.171.2.538","article-title":"Cutting edge: The conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule","volume":"171","author":"Hill","year":"2003","journal-title":"J. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1002\/art.39553","article-title":"A Novel HLA-DRB1*10:01-Restricted T Cell Epitope from Citrullinated Type II Collagen Relevant to Rheumatoid Arthritis","volume":"68","author":"Chemin","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Trier, N.H., Holm, B.E., Slot, O., Locht, H., Lindegaard, H., Svendsen, A., and Houen, G. (2016). Physical Characteristics of a Citrullinated Pro-Filaggrin Epitope Recognized by Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis Sera. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168542"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Sokolove, J., Bromberg, R., Deane, K.D., Lahey, L.J., Derber, L.A., Chandra, P.E., Edison, J.D., Gilliland, W.R., Tibshirani, R.J., and Norris, J.M. (2012). Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS ONE, 7.","DOI":"10.1371\/annotation\/2e462817-ab93-4d78-95a4-1d8b9d172971"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1136\/annrheumdis-2011-200421","article-title":"The ACPA recognition profile and subgrouping of ACPA-positive RA patients","volume":"71","author":"Willemze","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1002\/art.41385","article-title":"Different Hierarchies of Anti-Modified Protein Autoantibody Reactivities in Rheumatoid Arthritis","volume":"72","author":"Hansson","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/s41584-018-0070-0","article-title":"Rheumatoid arthritis and the mucosal origins hypothesis: Protection turns to destruction","volume":"14","author":"Holers","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"578129","DOI":"10.3389\/fimmu.2020.578129","article-title":"Neutrophil Extracellular Traps Tied to Rheumatoid Arthritis: Points to Ponder","volume":"11","author":"Song","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_130","first-page":"616","article-title":"Protein arginine deiminase 4 (PAD4): Current understanding and future therapeutic potential","volume":"12","author":"Jones","year":"2009","journal-title":"Curr. Opin. Drug Discov. Dev."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"eaag3358","DOI":"10.1126\/sciimmunol.aag3358","article-title":"Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis","volume":"2","author":"Carlucci","year":"2017","journal-title":"Sci. Immunol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/art.40760","article-title":"Affinity Maturation of the Anti-Citrullinated Protein Antibody Paratope Drives Epitope Spreading and Polyreactivity in Rheumatoid Arthritis","volume":"71","author":"Kongpachith","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1136\/annrheumdis-2019-216499","article-title":"Antibodies and B cells recognising citrullinated proteins display a broad cross-reactivity towards other post-translational modifications","volume":"79","author":"Kissel","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Wu, C.Y., Yang, H.Y., Luo, S.F., and Lai, J.H. (2021). From Rheumatoid Factor to Anti-Citrullinated Protein Antibodies and Anti-Carbamylated Protein Antibodies for Diagnosis and Prognosis Prediction in Patients with Rheumatoid Arthritis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020686"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1136\/annrheumdis-2016-210772","article-title":"Breach of autoreactive B cell tolerance by post-translationally modified proteins","volume":"76","author":"Dekkers","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"17372","DOI":"10.1073\/pnas.1114465108","article-title":"Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage","volume":"108","author":"Shi","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1136\/annrheumdis-2013-204154","article-title":"Anti-carbamylated protein (anti-CarP) antibodies precede the onset of rheumatoid arthritis","volume":"73","author":"Shi","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1002\/art.37830","article-title":"Anti-carbamylated protein antibodies are present in arthralgia patients and predict the development of rheumatoid arthritis","volume":"65","author":"Shi","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.acc.2017.12.001","article-title":"Protein Carbamylation: Chemistry, Pathophysiological Involvement, and Biomarkers","volume":"84","author":"Jaisson","year":"2018","journal-title":"Adv. Clin. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1042\/CS20080322","article-title":"Myeloperoxidase-mediated lipoprotein carbamylation as a mechanistic pathway for atherosclerotic vascular disease","volume":"116","author":"Sirpal","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1189\/jlb.1204697","article-title":"Myeloperoxidase: Friend and foe","volume":"77","author":"Klebanoff","year":"2005","journal-title":"J. Leukoc. Biol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/1479-5876-11-224","article-title":"Different amounts of protein-bound citrulline and homocitrulline in foot joint tissues of a patient with anti-citrullinated protein antibody positive erosive rheumatoid arthritis","volume":"11","author":"Turunen","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_143","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_144","doi-asserted-by":"crossref","unstructured":"Stoop, J.N., Liu, B.S., Shi, J., Jansen, D.T., Hegen, M., Huizinga, T.W., Trouw, L.A., and Toes, R.E. (2014). Antibodies specific for carbamylated proteins precede the onset of clinical symptoms in mice with collagen induced arthritis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102163"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1136\/annrheumdis-2018-214950","article-title":"Different classes of anti-modified protein antibodies are induced on exposure to antigens expressing only one type of modification","volume":"78","author":"Kampstra","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.1002\/art.27644","article-title":"Anticitrulline antibodies can be caused by homocitrulline-containing proteins in rabbits","volume":"62","author":"Turunen","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1136\/annrheumdis-2012-201559","article-title":"Recognition of citrullinated and carbamylated proteins by human antibodies: Specificity, cross-reactivity and the \u2018AMC-Senshu\u2019 method","volume":"72","author":"Shi","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3899\/jrheum.130742","article-title":"Antihomocitrullinated fibrinogen antibodies are specific to rheumatoid arthritis and frequently bind citrullinated proteins\/peptides","volume":"41","author":"Scinocca","year":"2014","journal-title":"J. Rheumatol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/s13075-021-02687-5","article-title":"Evolution of anti-modified protein antibody responses can be driven by consecutive exposure to different post-translational modifications","volume":"23","author":"Volkov","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1073\/pnas.1517096113","article-title":"Protein carbamylation is a hallmark of aging","volume":"113","author":"Gorisse","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1080\/03008207.2018.1449837","article-title":"Multiscale mechanical effects of native collagen cross-linking in tendon","volume":"59","author":"Eekhoff","year":"2018","journal-title":"Connect. Tissue Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1021\/acs.accounts.8b00092","article-title":"Collagen Structure-Function Relationships from Solid-State NMR Spectroscopy","volume":"51","author":"Goldberga","year":"2018","journal-title":"Acc. Chem. Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.chembiol.2005.11.005","article-title":"Impact of carbamylation on type I collagen conformational structure and its ability to activate human polymorphonuclear neutrophils","volume":"13","author":"Jaisson","year":"2006","journal-title":"Chem. Biol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.matbio.2017.06.004","article-title":"Aging-associated modifications of collagen affect its degradation by matrix metalloproteinases","volume":"65","author":"Panwar","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.matbio.2006.10.008","article-title":"Carbamylation differentially alters type I collagen sensitivity to various collagenases","volume":"26","author":"Jaisson","year":"2007","journal-title":"Matrix Biol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.matbio.2014.08.001","article-title":"Post-translational modifications of integrin ligands as pathogenic mechanisms in disease","volume":"40","author":"Zeltz","year":"2014","journal-title":"Matrix Biol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.freeradbiomed.2012.11.006","article-title":"Detection and isolation of human serum autoantibodies that recognize oxidatively modified autoantigens","volume":"57","author":"Eggleton","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.redox.2014.05.004","article-title":"Oxidative post-translational modifications and their involvement in the pathogenesis of autoimmune diseases","volume":"2","author":"Ryan","year":"2014","journal-title":"Redox Biol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1002\/art.21479","article-title":"Generation of neoantigenic epitopes after posttranslational modification of type II collagen by factors present within the inflamed joint","volume":"52","author":"Nissim","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Shahab, U., Ahmad, S., Dixit, K., Habib, S., Alam, K., and Ali, A. (2012). Hydroxyl radical modification of collagen type II increases its arthritogenicity and immunogenicity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031199"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1002\/art.37964","article-title":"Autoantibodies to posttranslationally modified type II collagen as potential biomarkers for rheumatoid arthritis","volume":"65","author":"Strollo","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Rodriguez-Martinez, L., Regueiro, C., Amhaz-Escanlar, S., Pena, C., Herbello-Hermelo, P., Moreda-Pineiro, A., Rodriguez-Garcia, J., Mera-Varela, A., Perez-Pampin, E., and Gonzalez, A. (2022). Antibodies against 4 Atypical Post-Translational Protein Modifications in Patients with Rheumatoid Arthritis. Diagnostics, 12.","DOI":"10.3390\/diagnostics12020352"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"18291","DOI":"10.1038\/s41598-019-54817-4","article-title":"Carbamylation and glycation compete for collagen molecular aging in vivo","volume":"9","author":"Nicolas","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"3957","DOI":"10.1021\/acs.jafc.8b00937","article-title":"Analysis of Advanced Glycation Endproducts in Rat Tail Collagen and Correlation to Tendon Stiffening","volume":"66","author":"Jost","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.matbio.2016.09.001","article-title":"Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue","volume":"59","author":"Gautieri","year":"2017","journal-title":"Matrix Biol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"R82","DOI":"10.1186\/ar622","article-title":"Advanced glycation end-product (AGE)-damaged IgG and IgM autoantibodies to IgG-AGE in patients with early synovitis","volume":"5","author":"Newkirk","year":"2003","journal-title":"Arthritis Res. Ther."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1136\/ard.61.6.488","article-title":"Identification of the advanced glycation end products N\u03b5-carboxymethyllysine in the synovial tissue of patients with rheumatoid arthritis","volume":"61","author":"Drinda","year":"2002","journal-title":"Ann. Rheum. Dis."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1093\/rheumatology\/38.12.1275","article-title":"Comparison of the concentrations of pentosidine in the synovial fluid, serum and urine of patients with rheumatoid arthritis and osteoarthritis","volume":"38","author":"Chen","year":"1999","journal-title":"Rheumatology"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.2741\/2030","article-title":"Transglutaminase 2 in inflammation","volume":"11","author":"Kim","year":"2006","journal-title":"Front. Biosci. (Landmark Ed.)"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1002\/eji.200939438","article-title":"Tissue transglutaminase enhances collagen type II-induced arthritis and modifies the immunodominant T-cell epitope CII260-270","volume":"39","author":"Dzhambazov","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"19263","DOI":"10.1038\/s41598-020-73919-y","article-title":"Improved classification of rheumatoid arthritis with a score including anti-acetylated ornithine antibodies","volume":"10","author":"Bang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"102470","DOI":"10.1016\/j.jaut.2020.102470","article-title":"Homocysteinylated alpha 1 antitrypsin as an antigenic target of autoantibodies in seronegative rheumatoid arthritis patients","volume":"113","author":"Colasanti","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref_173","first-page":"468","article-title":"Synovial fluid acidosis correlates with radiological joint destruction in rheumatoid arthritis knee joints","volume":"16","author":"Geborek","year":"1989","journal-title":"J. Rheumatol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1189\/jlb.69.4.522","article-title":"The effects of extracellular pH on immune function","volume":"69","author":"Lardner","year":"2001","journal-title":"J. Leukoc. Biol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jaut.2004.05.002","article-title":"A pH-induced modification of CII increases its arthritogenic properties","volume":"23","author":"Lundberg","year":"2004","journal-title":"J. Autoimmun."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Wang, H. (2021). A Review of the Effects of Collagen Treatment in Clinical Studies. Polymers, 13.","DOI":"10.3390\/polym13223868"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/j.1749-6632.1996.tb21138.x","article-title":"Evidence that type II collagen feeding can induce a durable therapeutic response in some patients with rheumatoid arthritis","volume":"778","author":"Trentham","year":"1996","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"105164","DOI":"10.1016\/j.jbspin.2021.105164","article-title":"Antigen-specific tolerance approach for rheumatoid arthritis: Past, present and future","volume":"88","author":"Page","year":"2021","journal-title":"Jt. Bone Spine"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1002\/art.1780390413","article-title":"A pilot trial of oral type II collagen in the treatment of juvenile rheumatoid arthritis","volume":"39","author":"Barnett","year":"1996","journal-title":"Arthritis Rheum."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.clim.2006.08.004","article-title":"Oral administration of type-II collagen peptide 250\u2013270 suppresses specific cellular and humoral immune response in collagen-induced arthritis","volume":"122","author":"Zhu","year":"2007","journal-title":"Clin. Immunol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"17345","DOI":"10.1038\/s41598-021-95193-2","article-title":"A fructosylated peptide derived from a collagen II T cell epitope for long-term treatment of arthritis (FIA-CIA) in mice","volume":"11","author":"Wenhart","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"5674","DOI":"10.4049\/jimmunol.1402457","article-title":"Immune tolerance induction with multiepitope peptide derived from citrullinated autoantigens attenuates arthritis manifestations in adjuvant arthritis rats","volume":"194","author":"Gertel","year":"2015","journal-title":"J. Immunol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"3916519","DOI":"10.1155\/2017\/3916519","article-title":"Immunomodulation of RA Patients\u2019 PBMC with a Multiepitope Peptide Derived from Citrullinated Autoantigens","volume":"2017","author":"Gertel","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"R201","DOI":"10.1186\/ar4039","article-title":"Validation of a multiplex chip-based assay for the detection of autoantibodies against citrullinated peptides","volume":"14","author":"Hansson","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_185","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_186","doi-asserted-by":"crossref","first-page":"577015","DOI":"10.3389\/fimmu.2020.577015","article-title":"Tenascin-C in Osteoarthritis and Rheumatoid Arthritis","volume":"11","author":"Hasegawa","year":"2020","journal-title":"Front. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/12\/9884\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:50:33Z","timestamp":1760125833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/12\/9884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,8]]},"references-count":186,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ijms24129884"],"URL":"https:\/\/doi.org\/10.3390\/ijms24129884","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,8]]}}}