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These autoantibodies, influenced by genetic and environmental factors, play a crucial role in RA pathogenesis through post-translational modifications like citrullination, carbamylation, and acetylation. The early detection of ACPA provides a potential window for intervention, while anti-CarP antibodies correlate with severe disease progression and RF aids in diagnosis. Translating these findings from human pathology to animal models presents significant challenges. Although the presence of adaptative immune cells (T cells) is well defined in animal models of RA, studies yield inconsistent results regarding autoantibody production and implication in the disease onset and progression, with varying detectability of ACPA, anti-CarP antibodies, and RF across different species and models. The collagen-induced arthritis (CIA) model shows PAD4 expression and citrullinated protein presence but inconsistent ACPA detection, while the K\/BxN model elucidates the pathogenicity of anti-GPI autoantibodies and implicates Fc\u03b3 receptors in disease processes. Therefore, further research is needed to bridge the gap between animal models and human RA pathology. Future studies should focus on developing more representative animal models, exploring pharmacological targets and pathways that involve the interplay between anti-inflammatory and autoimmune responses, and investigating the complex interplay between genetic predisposition, environmental triggers, and autoimmune mechanisms. This approach may lead to improved early diagnostic tools, targeted therapies, and potentially preventive strategies for RA, ultimately enhancing patient outcomes and quality of life.<\/jats:p>","DOI":"10.3390\/biology14050460","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T08:08:41Z","timestamp":1745482121000},"page":"460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Animal Models in Rheumatoid Arthritis: Is There a Correlation Between Autoantibodies in Human Pathology and Animal Models?"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5103-0327","authenticated-orcid":false,"given":"Miguel","family":"Marco-Bonilla","sequence":"first","affiliation":[{"name":"Joint and Bone Research Unit, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5138-1857","authenticated-orcid":false,"given":"Maria","family":"Fresnadillo","sequence":"additional","affiliation":[{"name":"Joint and Bone Research Unit, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2263-901X","authenticated-orcid":false,"given":"Macarena","family":"de la Riva-Bueno","sequence":"additional","affiliation":[{"name":"Joint and Bone Research Unit, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3241-991X","authenticated-orcid":false,"given":"Gabriel","family":"Herrero-Beaumont","sequence":"additional","affiliation":[{"name":"Joint and Bone Research Unit, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6525-2944","authenticated-orcid":false,"given":"Raquel","family":"Largo","sequence":"additional","affiliation":[{"name":"Joint and Bone Research Unit, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5368-574X","authenticated-orcid":false,"given":"Ar\u00e1nzazu","family":"Mediero","sequence":"additional","affiliation":[{"name":"Joint and Bone Research Unit, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"ref_1","first-page":"e32","article-title":"Schubach Abigail What Is Rheumatoid Arthritis?","volume":"390","author":"Natalie","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41584-022-00793-5","article-title":"Mechanisms of Joint Destruction in Rheumatoid Arthritis\u2014Immune Cell\u2013Fibroblast\u2013Bone Interactions","volume":"18","author":"Komatsu","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41577-024-00994-x","article-title":"The Regulation and Differentiation of Regulatory T Cells and Their Dysfunction in Autoimmune Diseases","volume":"24","author":"Sumida","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yang, M., and Zhu, L. (2024). Osteoimmunology: The Crosstalk between T Cells, B Cells, and Osteoclasts in Rheumatoid Arthritis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052688"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.molmed.2018.12.008","article-title":"Neutrophils in Rheumatoid Arthritis: Breaking Immune Tolerance and Fueling Disease","volume":"25","author":"Kaplan","year":"2019","journal-title":"Trends Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.bj.2020.06.010","article-title":"Innate Immunity Drives Pathogenesis of Rheumatoid Arthritis","volume":"44","author":"Edilova","year":"2021","journal-title":"Biomed. J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Prieto-Potin, I., Largo, R., Roman-Blas, J.A., Herrero-Beaumont, G., and Walsh, D.A. (2015). Characterization of Multinucleated Giant Cells in Synovium and Subchondral Bone in Knee Osteoarthritis and Rheumatoid Arthritis. BMC Musculoskelet Disord, 16.","DOI":"10.1186\/s12891-015-0664-5"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ishikawa, Y., and Terao, C. (2020). The Impact of Cigarette Smoking on Risk of Rheumatoid Arthritis: A Narrative Review. Cells, 9.","DOI":"10.3390\/cells9020475"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wysocki, T., Olesi\u0144ska, M., and Paradowska-Gorycka, A. (2020). Current Understanding of an Emerging Role of HLA-DRB1 Gene in Rheumatoid Arthritis\u2013From Research to Clinical Practice. Cells, 9.","DOI":"10.3390\/cells9051127"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e125278","DOI":"10.1172\/jci.insight.125278","article-title":"Antibody-Dependent and -Independent Mechanisms of Inflammatory Arthritis","volume":"4","author":"Chang","year":"2019","journal-title":"JCI Insight"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.12701\/jyms.2022.00773","article-title":"The Use of Animal Models in Rheumatoid Arthritis Research","volume":"40","author":"Kong","year":"2023","journal-title":"J. Yeungnam Med. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhao, T., Xie, Z., Xi, Y., Liu, L., Li, Z., and Qin, D. (2022). How to Model Rheumatoid Arthritis in Animals: From Rodents to Non-Human Primates. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.887460"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101729","DOI":"10.1016\/j.jcot.2021.101729","article-title":"Anti-Cyclic Citrullinated Peptide Antibody (ACPA) and Rheumatoid Arthritis: Clinical Relevance","volume":"24","author":"Iyengar","year":"2022","journal-title":"J. Clin. Orthop. Trauma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jbspin.2004.12.012","article-title":"Where Do T Cells Stand in Rheumatoid Arthritis?","volume":"72","author":"Fournier","year":"2005","journal-title":"Jt. Bone Spine"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Stoop, J.N., Liu, B.-S., Shi, J., Jansen, D.T.S.L., Hegen, M., Huizinga, T.W.J., Trouw, L.A., and Toes, R.E.M. (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_16","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1136\/annrheumdis-2014-206797","article-title":"Anticarbamylated Protein Antibodies Can Be Detected in Animal Models of Arthritis That Require Active Involvement of the Adaptive Immune System","volume":"74","author":"Stoop","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1136\/ard.46.1.65","article-title":"IgM Rheumatoid Factor (RF), IgA RF, IgE RF, and IgG RF Detected by ELISA in Rheumatoid Arthritis","volume":"46","author":"Auvinet","year":"1987","journal-title":"Ann. Rheum. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Maibom-Thomsen, S.L., Trier, N.H., Holm, B.E., Hansen, K.B., Rasmussen, M.I., Chailyan, A., Marcatili, P., H\u00f8jrup, P., and Houen, G. (2019). Immunoglobulin G Structure and Rheumatoid Factor Epitopes. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0217624"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"441","DOI":"10.4049\/jimmunol.63.4.441","article-title":"Serological Reactions in Rheumatoid Arthritis: I. Factors Affecting the Agglutination of Sensitized Sheep Erythrocytes in Rheumatoid-Arthritis Serum1","volume":"63","author":"Pike","year":"1949","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1136\/ard.19.2.163","article-title":"On the Nature of the Rheumatoid Factor","volume":"19","author":"Hofmann","year":"1960","journal-title":"Ann. Rheum Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/art.1780310302","article-title":"The American Rheumatism Association 1987 Revised Criteria for the Classification of Rheumatoid Arthritis","volume":"31","author":"Arnett","year":"1988","journal-title":"Arthritis Rheum."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1128\/jcm.22.1.89-94.1985","article-title":"Rheumatoid Factor in Syphilis","volume":"22","author":"Cerny","year":"1985","journal-title":"J. Clin. Microbiol"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1046\/j.1365-2249.1999.00963.x","article-title":"Rheumatoid Factors in Primary Sj\u00f6gren\u2019s Syndrome (pSS) Use Diverse VH Region Genes, the Majority of Which Show No Evidence of Somatic Hypermutation","volume":"117","author":"Elagib","year":"2001","journal-title":"Clin. Exp. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1136\/ard.2005.045229","article-title":"Positive Anti-Cyclic Citrullinated Proteins and Rheumatoid Factor during Active Lung Tuberculosis","volume":"65","author":"Elkayam","year":"2006","journal-title":"Ann. Rheum. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s00296-018-4021-5","article-title":"Clinical Connection between Rheumatoid Arthritis and Liver Damage","volume":"38","author":"Zivkovic","year":"2018","journal-title":"Rheumatol Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102528","DOI":"10.1016\/j.autrev.2020.102528","article-title":"Rheumatoid Arthritis in the Elderly: Characteristics and Treatment Considerations","volume":"19","author":"Serhal","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s002960050112","article-title":"Rheumatoid Factors in Systemic Lupus Erythematosus: Association with Clinical and Laboratory Parameters","volume":"19","author":"Witte","year":"2000","journal-title":"Rheumatol. Int."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nicol\u00f2, A., Amendt, T., El Ayoubi, O., Young, M., Finzel, S., Senel, M., Voll, R.E., and Jumaa, H. (2022). Rheumatoid Factor IgM Autoantibodies Control IgG Homeostasis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1016263"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e002817","DOI":"10.1136\/rmdopen-2022-002817","article-title":"Rheumatoid Factor Isotypes in Rheumatoid Arthritis Diagnosis and Prognosis: A Systematic Review and Meta-Analysis","volume":"9","author":"Motta","year":"2023","journal-title":"RMD Open"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1136\/ard-2023-224728","article-title":"In Early Rheumatoid Arthritis, Anticitrullinated Peptide Antibodies Associate with Low Number of Affected Joints and Rheumatoid Factor Associates with Systemic Inflammation","volume":"83","author":"Pertsinidou","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1002\/art.38307","article-title":"Rheumatoid Factor as a Potentiator of Anti\u2013Citrullinated Protein Antibody\u2013Mediated Inflammation in Rheumatoid Arthritis","volume":"66","author":"Sokolove","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1002\/art.24827","article-title":"Anti\u2013Citrullinated Peptide Antibody Assays and Their Role in the Diagnosis of Rheumatoid Arthritis","volume":"61","author":"Aggarwal","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_33","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_34","doi-asserted-by":"crossref","first-page":"1759720X211022533","DOI":"10.1177\/1759720X211022533","article-title":"Presence of Anti-Acetylated Peptide Antibodies (AAPA) in Inflammatory Arthritis and Other Rheumatic Diseases Suggests Discriminative Diagnostic Capacity towards Early Rheumatoid Arthritis","volume":"13","author":"Studenic","year":"2021","journal-title":"Ther. Adv. Musculoskelet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"818","DOI":"10.4236\/abb.2013.48108","article-title":"The Diagnostic Significance of Glucose-6-Phosphate Isomerase (G6PI) Antigen and Anti-G6PI Antibody in Rheumatoid Arthritis Patients","volume":"04","author":"Yang","year":"2013","journal-title":"Adv. Biosci. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3109\/s10165-006-0498-y","article-title":"Autoimmunity to Citrullinated Type II Collagen in Rheumatoid Arthritis","volume":"16","author":"Yoshida","year":"2006","journal-title":"Mod. Rheumatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"vi5","DOI":"10.1093\/rheumatology\/kes279","article-title":"ACR\/EULAR 2010 Rheumatoid Arthritis Classification Criteria","volume":"51","author":"Kay","year":"2012","journal-title":"Rheumatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s41467-023-36257-x","article-title":"A Subset of Antibodies Targeting Citrullinated Proteins Confers Protection from Rheumatoid Arthritis","volume":"14","author":"He","year":"2023","journal-title":"Nat. Commun"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41584-020-0409-1","article-title":"PAD Enzymes in Rheumatoid Arthritis: Pathogenic Effectors and Autoimmune Targets","volume":"16","author":"Curran","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_40","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_41","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_42","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_43","doi-asserted-by":"crossref","unstructured":"Zhao, J., Jiang, P., Guo, S., Schrodi, S.J., and He, D. (2021). Apoptosis, Autophagy, NETosis, Necroptosis, and Pyroptosis Mediated Programmed Cell Death as Targets for Innovative Therapy in Rheumatoid Arthritis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.809806"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lloyd, K.A., Wigerblad, G., Sahlstr\u00f6m, P., Garimella, M.G., Chemin, K., Steen, J., Titcombe, P.J., Marklein, B., Zhou, D., and St\u00e5lesen, R. (2019). Differential ACPA Binding to Nuclear Antigens Reveals a PAD-Independent Pathway and a Distinct Subset of Acetylation Cross-Reactive Autoantibodies in Rheumatoid Arthritis. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.03033"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Corsiero, E., Pratesi, F., Prediletto, E., Bombardieri, M., and Migliorini, P. (2016). NETosis as Source of Autoantigens in Rheumatoid Arthritis. Front. Immunol.","DOI":"10.3389\/fimmu.2016.00485"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Reis, L.R., Souza Junior, D.R., Tomasin, R., Bruni-Cardoso, A., Di Mascio, P., and Ronsein, G.E. (2023). Citrullination of Actin-Ligand and Nuclear Structural Proteins, Cytoskeleton Reorganization and Protein Redistribution across Cellular Fractions Are Early Events in Ionomycin-Induced NETosis. Redox Biol., 64.","DOI":"10.1016\/j.redox.2023.102784"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, J., Gao, J., Wu, Z., Mi, L., Li, N., Wang, Y., Peng, X., Xu, K., Wu, F., and Zhang, L. (2022). Anti-Citrullinated Protein Antibody Generation, Pathogenesis, Clinical Application, and Prospects. Front. Med., 8.","DOI":"10.3389\/fmed.2021.802934"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1093\/rheumatology\/keae146","article-title":"Identification of Early Risk Factors for Anti-Citrullinated-Protein-Antibody Positive Rheumatoid Arthritis\u2014A Prospective Cohort Study","volume":"63","author":"Kisten","year":"2024","journal-title":"Rheumatology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/cei.13206","article-title":"Changes in Anti-Citrullinated Protein Antibody Isotype Levels in Relation to Disease Activity and Response to Treatment in Early Rheumatoid Arthritis","volume":"194","author":"Kastbom","year":"2018","journal-title":"Clin. Exp. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/s13075-017-1392-z","article-title":"The Isotype and IgG Subclass Distribution of Anti-Carbamylated Protein Antibodies in Rheumatoid Arthritis Patients","volume":"19","author":"Verheul","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"A38","DOI":"10.1136\/ard.2010.148973.6","article-title":"Cytokine Profile of Macrophages in Vitro Stimulated by ACPA Immune Complexes in the Presence or Absence of IgM Rheumatoid Factor","volume":"70","author":"Laurent","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_52","first-page":"284","article-title":"Fc Gamma Receptor Binding Profile of Anti-Citrullinated Protein Antibodies in Immune Complexes Suggests a Role for Fc\u03b3RI in the Pathogenesis of Synovial Inflammation","volume":"36","author":"Kempers","year":"2018","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e34088","DOI":"10.1016\/j.heliyon.2024.e34088","article-title":"Immunophenotypic Landscape of Synovial Tissue in Rheumatoid Arthritis: Insights from ACPA Status","volume":"10","author":"Li","year":"2024","journal-title":"Heliyon"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kurowska, W., Slowinska, I., Krogulec, Z., Syrowka, P., and Maslinski, W. (2021). Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10081778"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Cunningham, K.Y., Hur, B., Gupta, V.K., Arment, C.A., Wright, K.A., Mason, T.G., Peterson, L.S., Bekele, D.I., Schaffer, D.E., and Bailey, M.L. (2023). Patients with ACPA-Positive and ACPA-Negative Rheumatoid Arthritis Show Different Serological Autoantibody Repertoires and Autoantibody Associations with Disease Activity. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-32428-4"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1136\/annrheumdis-2017-211325","article-title":"Differences in the Symptomatic Phase Preceding ACPA-Positive and ACPA-Negative RA: A Longitudinal Study in Arthralgia during Progression to Clinical Arthritis","volume":"76","author":"Burgers","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.autrev.2013.08.002","article-title":"HLA Shared Epitope and ACPA: Just a Marker or an Active Player?","volume":"12","author":"Pratesi","year":"2013","journal-title":"Autoimmun. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Roudier, J., Balandraud, N., and Auger, I. (2022). How RA Associated HLA-DR Molecules Contribute to the Development of Antibodies to Citrullinated Proteins: The Hapten Carrier Model. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.930112"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.1002\/art.21302","article-title":"Association of HLA\u2013DR3 with Anti\u2013Cyclic Citrullinated Peptide Antibody\u2013Negative Rheumatoid Arthritis","volume":"52","author":"Verpoort","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s00251-017-0987-5","article-title":"HLA Class II and Rheumatoid Arthritis: The Bumpy Road of Revelation","volume":"69","author":"Kampstra","year":"2017","journal-title":"Immunogenetics"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1002\/art.40920","article-title":"N -Linked Glycans in the Variable Domain of IgG Anti\u2013Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis","volume":"71","author":"Hafkenscheid","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1002\/eji.202249889","article-title":"PAD2 Immunization Induces ACPA in Wild-type and HLA-DR4 Humanized Mice","volume":"52","author":"Hemon","year":"2022","journal-title":"Eur. J. Immunol"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1002\/art.24385","article-title":"Quantitative Heritability of Anti\u2013Citrullinated Protein Antibody\u2013Positive and Anti\u2013Citrullinated Protein Antibody\u2013Negative Rheumatoid Arthritis","volume":"60","author":"Toes","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1093\/rheumatology\/kem006","article-title":"Risk of Progression from Undifferentiated Arthritis to Rheumatoid Arthritis: The Effect of the PTPN22 1858T-Allele in Anti-Citrullinated Peptide Antibody Positive Patients","volume":"46","author":"Feitsma","year":"2007","journal-title":"Rheumatology"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Massarenti, L., Enevold, C., Damgaard, D., \u00d8dum, N., Garred, P., Frisch, M., Shelef, M.A., Jacobsen, S., and Nielsen, C.H. (2021). PADI4 Polymorphisms Confer Risk of Anti-CCP-Positive Rheumatoid Arthritis in Synergy With HLA-DRB1*04 and Smoking. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.707690"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11926-016-0563-2","article-title":"The Roles of Cigarette Smoking and the Lung in the Transitions Between Phases of Preclinical Rheumatoid Arthritis","volume":"18","author":"Sparks","year":"2016","journal-title":"Curr. Rheumatol Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"109936","DOI":"10.1016\/j.intimp.2023.109936","article-title":"Impacts of Porphyromonas Gingivalis Periodontitis on Rheumatoid Arthritis Autoimmunity","volume":"118","author":"Ahmadi","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_68","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_69","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1097\/BOR.0000000000000452","article-title":"Rheumatoid Arthritis and Citrullination","volume":"30","author":"Darrah","year":"2018","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Pruijn, G.J.M. (2015). Citrullination and Carbamylation in the Pathophysiology of Rheumatoid Arthritis. Front. Immunol.","DOI":"10.3389\/fimmu.2015.00192"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1136\/annrheumdis-2013-205109","article-title":"Anti-CarP Antibodies in Two Large Cohorts of Patients with Rheumatoid Arthritis and Their Relationship to Genetic Risk Factors, Cigarette Smoking and Other Autoantibodies","volume":"73","author":"Jiang","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1134\/S1607672924700960","article-title":"Anti-Carbamylated Protein Antibodies in ACPA-Negative and ACPA-Positive Patients with Rheumatoid Arthritis","volume":"517","author":"Dibrov","year":"2024","journal-title":"Dokl. Biochem. Biophys."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"eabd2688","DOI":"10.1126\/sciadv.abd2688","article-title":"Neutrophil-Mediated Carbamylation Promotes Articular Damage in Rheumatoid Arthritis","volume":"6","author":"Aponte","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1093\/rheumatology\/key174","article-title":"Autophagy Induces Protein Carbamylation in Fibroblast-like Synoviocytes from Patients with Rheumatoid Arthritis","volume":"57","author":"Manganelli","year":"2018","journal-title":"Rheumatology"},{"key":"ref_75","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_76","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/art.40738","article-title":"Specific Association of HLA\u2014DRB 1*03 with Anti\u2013Carbamylated Protein Antibodies in Patients With Rheumatoid Arthritis","volume":"71","author":"Regueiro","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_77","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_78","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1093\/ndt\/15.8.1183","article-title":"Kinetics of Carbamylated Haemoglobin in Acute Renal Failure","volume":"15","author":"Wynckel","year":"2000","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_79","first-page":"877","article-title":"Altered Acetylation of Proteins in Patients with Rheumatoid Arthritis Revealed by Acetyl-Proteomics","volume":"33","author":"Arito","year":"2025","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_80","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_81","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/90696","article-title":"Autoantibodies to GPI in Rheumatoid Arthritis: Linkage between an Animal Model and Human Disease","volume":"2","author":"Schaller","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_82","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_83","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1002\/art.1780391015","article-title":"Antibodies to Type II Collagen in Early Rheumatoid Arthritis. Correlation with Disease Progression","volume":"39","author":"Cook","year":"1996","journal-title":"Arthritis Rheum."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1136\/ard.2006.064782","article-title":"High Anti-Collagen Type-II Antibody Levels and Induction of Proinflammatory Cytokines by Anti-Collagen Antibody-Containing Immune Complexes in Vitro Characterise a Distinct Rheumatoid Arthritis Phenotype Associated with Acute Inflammation at the Time of Disease Onset","volume":"66","author":"Mullazehi","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1002\/art.23765","article-title":"Chronic Arthritis Aggravates Vascular Lesions in Rabbits with Atherosclerosis: A Novel Model of Atherosclerosis Associated with Chronic Inflammation","volume":"58","author":"Largo","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Little, R.D., Prieto-Potin, I., P\u00e9rez-Baos, S., Villalvilla, A., Gratal, P., Cicuttini, F., Largo, R., and Herrero-Beaumont, G. (2017). Compensatory Anabolic Signaling in the Sarcopenia of Experimental Chronic Arthritis. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-06581-6"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1111\/bph.13932","article-title":"Tofacitinib Restores the Inhibition of Reverse Cholesterol Transport Induced by Inflammation: Understanding the Lipid Paradox Associated with Rheumatoid Arthritis","volume":"174","author":"Barrasa","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1172\/JCI25422","article-title":"Antibodies against Citrullinated Proteins Enhance Tissue Injury in Experimental Autoimmune Arthritis","volume":"116","author":"Kuhn","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1002\/art.11229","article-title":"Citrullination of Synovial Proteins in Murine Models of Rheumatoid Arthritis","volume":"48","author":"Vossenaar","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"R119","DOI":"10.1186\/ar2523","article-title":"Epitope Spreading to Citrullinated Antigens in Mouse Models of Autoimmune Arthritis and Demyelination","volume":"10","author":"Kidd","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Kim, J.-W., Jung, H., Baek, I.-P., Nam, Y., Kang, J., Chung, M.K., Park, J.-B., Lee, J., Kwok, S.-K., and Kim, W.-U. (2022). Differential Effects of Periodontal Microbiome on the Rheumatoid Factor Induction during Rheumatoid Arthritis Pathogenesis. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-21788-y"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Zhao, X., Long, J., Liang, F., Liu, N., Sun, Y., and Xi, Y. (2021). 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. Biomed. Pharmacother., 144.","DOI":"10.1016\/j.biopha.2021.112294"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/s13075-017-1455-1","article-title":"Anti-Carbamylated Protein Antibodies Precede Disease Onset in Monkeys with Collagen-Induced Arthritis","volume":"19","author":"Verheul","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4663","DOI":"10.2147\/JIR.S378090","article-title":"AMPK\/SIRT1 Deficiency Drives Adjuvant-Induced Arthritis in Rats by Promoting Glycolysis-Mediated Monocytes Inflammatory Polarization","volume":"15","author":"Wang","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_95","first-page":"1","article-title":"Potency of Bone Marrow-Derived Mesenchymal Stem Cells and Indomethacin in Complete Freund\u2019s Adjuvant-Induced Arthritic Rats: Roles of TNF-\u03b1, IL-10, iNOS, MMP-9, and TGF-\u03921","volume":"2021","author":"Ahmed","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"R104","DOI":"10.1186\/ar3829","article-title":"PAD4 Is Not Essential for Disease in the K\/BxN Murine Autoantibody-Mediated Model of Arthritis","volume":"14","author":"Rohrbach","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.4049\/jimmunol.1003642","article-title":"Cutting Edge: The Murine High-Affinity IgG Receptor Fc Gamma RIV Is Sufficient for Autoantibody-Induced Arthritis","volume":"186","author":"Mancardi","year":"2011","journal-title":"J. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1084\/jem.20011941","article-title":"Arthritogenic Monoclonal Antibodies from K\/BxN Mice","volume":"195","author":"Maccioni","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"529","DOI":"10.4062\/biomolther.2022.071","article-title":"A Novel Therapeutic Effect of a New Variant of CTLA4-Ig with Four Antennas That Are Terminally Capped with Sialic Acid in the CTLA4 Region","volume":"30","author":"Piao","year":"2022","journal-title":"Biomol Ther."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/5\/460\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:20:44Z","timestamp":1760030444000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/5\/460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,24]]},"references-count":99,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["biology14050460"],"URL":"https:\/\/doi.org\/10.3390\/biology14050460","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,24]]}}}