{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:22:13Z","timestamp":1792628533982,"version":"4.5.0"},"reference-count":93,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Seronegative rheumatoid arthritis (SNRA), defined by the absence of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), represents 20\u201330% of rheumatoid arthritis cases. Once considered a milder phenotype, SNRA is now recognised as a heterogeneous entity in which a substantial subset of patients develops structural progression comparable to seropositive RA. The binary RF\/ACPA-based definition is increasingly viewed as insufficient, as the broader anti-modified protein antibody (AMPA) family\u2014including antibodies against carbamylated, acetylated and malondialdehyde\u2013acetaldehyde\u2013modified proteins\u2014indicates that many \u201cseronegative\u201d patients may harbour unconventional humoral autoimmunity undetected by standard assays. Objectives: To synthesise contemporary insights into the epidemiology, immunopathology, diagnostic challenges and therapeutic management of SNRA, with emphasis on erosive versus non-erosive phenotypes and the implications of the AMPA paradigm. Methods: A comprehensive literature search of PubMed, Cochrane Library and Google Scholar identified randomised trials, observational cohorts and systematic reviews, with focus on studies published within the past decade. Results: SNRA displays partially distinct immune features, including lower formation of tertiary lymphoid structures and variable activation of innate inflammatory circuits. However, the traditional adaptive\u2013versus\u2013innate dichotomy is overly reductionist. Growing evidence suggests that unconventional humoral responses directed against non-classical post-translational modifications may be present in a proportion of RF\/ACPA-negative patients. Additional qualitative dimensions\u2014such as IgA isotypes and fine-specificity profiles\u2014represent further heterogeneity with potential prognostic significance. Although ACPA remains the strongest predictor of erosive progression, up to one-third of seronegative patients develop erosions within five years. The 2010 ACR\/EULAR criteria may delay diagnosis in SNRA. Cytokine inhibitors and JAK inhibitors show largely serostatus-independent efficacy, whereas B-cell and T-cell\u2013targeted therapies demonstrate attenuated responses in SNRA. Conclusions: SNRA is clinically and immunologically diverse. Integrating the AMPA framework is essential for refining classification and prognostication. Distinguishing erosive from non-erosive forms may guide treatment, while future work should prioritise biomarkers predicting progression and therapeutic response.<\/jats:p>","DOI":"10.3390\/medsci14010014","type":"journal-article","created":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T23:54:36Z","timestamp":1766966076000},"page":"14","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Seronegative Rheumatoid Arthritis: A Distinct Immunopathological Entity with Erosive Potential"],"prefix":"10.3390","volume":"14","author":[{"given":"Florent","family":"Lhotellerie","sequence":"first","affiliation":[{"name":"Department of Rheumatology, H\u00f4pital Universitaire de Bruxelles, Universit\u00e9 libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8380-4618","authenticated-orcid":false,"given":"Ala Eddine","family":"Ben Ismail","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, H\u00f4pital Universitaire de Bruxelles, Universit\u00e9 libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6833-0044","authenticated-orcid":false,"given":"Julie","family":"Sarrand","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, H\u00f4pital Universitaire de Bruxelles, Universit\u00e9 libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9051-1810","authenticated-orcid":false,"given":"Muhammad","family":"Soyfoo","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, H\u00f4pital Universitaire de Bruxelles, Universit\u00e9 libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,28]]},"reference":[{"key":"ref_1","first-page":"591","article-title":"Global epidemiology of rheumatoid arthritis","volume":"18","author":"Finckh","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1093\/rheumatology\/keaa393","article-title":"The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: Results from a collaboration of 16 registries","volume":"60","author":"Courvoisier","year":"2021","journal-title":"Rheumatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.3899\/jrheum.111125","article-title":"Long-term retention of tumor necrosis factor-inhibitor therapy in a large italian cohort of patients with rheumatoid arthritis from the GISEA registry: An appraisal of predictors","volume":"39","author":"Iannone","year":"2012","journal-title":"J. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"vii54","DOI":"10.1093\/rheumatology\/key109","article-title":"Randomized controlled trials and real-world data: Differences and similarities to untangle literature data","volume":"57","author":"Monti","year":"2018","journal-title":"Rheumatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105869","DOI":"10.1016\/j.jbspin.2025.105869","article-title":"Could the anti-modified protein antibody concept help better define seronegative rheumatoid arthritis?","volume":"92","author":"Brevet","year":"2025","journal-title":"Jt. Bone Spine"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Svensson, B., Andersson, M.L.E., Gjertsson, I., Hafstr\u00f6m, I., and Forslind, K. (2022). Erosion-free rheumatoid arthritis: Clinical and conceptional implications\u2014A BARFOT study. BMC Rheumatol., 6.","DOI":"10.1186\/s41927-022-00317-4"},{"key":"ref_7","first-page":"261","article-title":"How to read radiographs according to the Sharp\/van der Heijde method","volume":"27","year":"2000","journal-title":"J. Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1136\/annrheumdis-2012-203158","article-title":"EULAR Recommendations for the Use of Imaging of the Joints in the Clinical Management of Rheumatoid Arthritis","volume":"72","author":"Colebatch","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"105823","DOI":"10.1016\/j.jbspin.2024.105823","article-title":"Clinical presentation and treatment response in ACPA-negative rheumatoid arthritis","volume":"92","author":"Chevet","year":"2025","journal-title":"Jt. Bone Spine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"26","DOI":"10.17305\/bjbms.2010.2729","article-title":"Extra-articular manifestations of seronegative and seropositive rheumatoid arthritis","volume":"10","author":"Rexhepi","year":"2010","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.1136\/annrheumdis-2020-217609","article-title":"Increasing incidence of autoantibody-negative RA is replicated and is partly explained by an aging population","volume":"81","author":"Matthijssen","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1136\/annrheumdis-2019-216694","article-title":"Is the epidemiology of rheumatoid arthritis changing? Results from a population-based incidence study, 1985\u20132014","volume":"79","author":"Myasoedova","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"369ra176","DOI":"10.1126\/scitranslmed.aaj1921","article-title":"Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis","volume":"8","author":"Konig","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1177\/0022034518805739","article-title":"The oral microbiota is modified by systemic diseases","volume":"98","author":"Graves","year":"2019","journal-title":"J. Dent. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"De Stefano, L., D\u2019Onofrio, B., Manzo, A., Sakellariou, G., Bugatti, S., and Montecucco, C. (2021). The genetic, environmental, and immunopathological complexity of autoantibody-negative rheumatoid arthritis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212386"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chang, C., and Lu, Q. (2022). MicroRNA-mediated epigenetic regulation of rheumatoid arthritis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.838884"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1093\/rheumatology\/kead378","article-title":"Synovial and serum B-cell signature of autoantibody-negative rheumatoid arthritis versus autoantibody-positive rheumatoid arthritis and psoriatic arthritis","volume":"63","author":"Bugatti","year":"2024","journal-title":"Rheumatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4977","DOI":"10.1038\/s41467-021-25246-7","article-title":"Single-cell sequencing of immune cells from anticitrullinated peptide antibody\u2013positive and \u2013negative rheumatoid arthritis","volume":"12","author":"Wu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1186\/ar113","article-title":"Fibroblast biology: Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis","volume":"2","author":"Pap","year":"2000","journal-title":"Arthritis Res. Ther."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s13075-018-1591-2","article-title":"Does information on novel identified autoantibodies contribute to predicting the progression from undifferentiated arthritis to rheumatoid arthritis: A study on anti-CarP antibodies as an example","volume":"20","author":"Boeters","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e284","DOI":"10.1016\/S2665-9913(20)30381-7","article-title":"Scottish Early Rheumatoid Arthritis Inception Cohort Investigators.. The impact of autoantibodies against citrullinated, carbamylated, and acetylated peptides on radiographic progression in patients with new-onset rheumatoid arthritis: An observational cohort study","volume":"3","author":"Nijjar","year":"2021","journal-title":"Lancet Rheumatol."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1093\/rheumatology\/kead545","article-title":"Diagnostic values, association with disease activity and possible risk factors of anti-PAD4 in rheumatoid arthritis: A meta-analysis","volume":"63","author":"Zhang","year":"2023","journal-title":"Rheumatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1007\/s10067-017-3809-0","article-title":"Meta-analysis: Diagnostic accuracy of antibody against peptidylarginine deiminase 4 by ELISA for rheumatoid arthritis","volume":"36","author":"Ren","year":"2017","journal-title":"Clin. Rheumatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"120288","DOI":"10.1016\/j.cca.2025.120288","article-title":"Biomarkers for early diagnosis of rheumatoid arthritis","volume":"574","author":"Yi","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Floris, A., Angioni, M.M., Fadda, M., Naitza, M.R., Congia, M., Chessa, E., Piga, M., and Cauli, A. (2025). The role of anti-PAD4, anti-CarP, and anti-RA33 antibodies combined with RF and ACPA in predicting abatacept response in rheumatoid arthritis. Arthritis Res. Ther., 27, 9.","DOI":"10.1186\/s13075-024-03470-y"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1002\/art.30371","article-title":"Favorable effect of very early disease-modifying antirheumatic drug treatment on radiographic progression in early inflammatory arthritis: Data from the \u00c9tude et Suivi des Polyarthrites Indiff\u00e9Renci\u00e9es r\u00e9centes (Study and Followup of Early Undifferentiated Polyarthritis.)","volume":"63","author":"Lukas","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/annrheumdis-2019-216655","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update","volume":"79","author":"Smolen","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1136\/ard.2010.138461","article-title":"2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"69","author":"Aletaha","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_31","first-page":"313","article-title":"Rheumatoid arthritis classification criteria: Updated perspectives","volume":"43","author":"Sparks","year":"2017","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/art.22380","article-title":"A prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis: How to guide individual treatment decisions","volume":"56","author":"Breedveld","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref_33","first-page":"1024","article-title":"Clinical and serological factors associated with radiographic progression in early arthritis: A meta-analysis","volume":"74","author":"Huizinga","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_34","first-page":"2278","article-title":"Very recent onset arthritis\u2014Clinical, laboratory, and radiological findings during the first year of disease","volume":"29","author":"Machold","year":"2002","journal-title":"J. Rheumatol."},{"key":"ref_35","first-page":"2101","article-title":"Rheumatoid arthritis subgroups: Patients with negative rheumatoid factor in long-term clinical studies","volume":"25","author":"Pincus","year":"1998","journal-title":"J. Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1136\/annrheumdis-2015-208873","article-title":"Patients with seronegative RA have more inflammatory activity compared with patients with seropositive RA in an inception cohort of DMARD-na\u00efve patients classified according to the 2010 ACR\/EULAR criteria","volume":"76","author":"Nordberg","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1136\/ard.2004.033571","article-title":"Longitudinal analysis of citrullinated protein\/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: Anti-CP status predicts worse disease activity and greater radiological progression","volume":"64","author":"Wick","year":"2005","journal-title":"Ann. Rheum. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.3899\/jrheum.140082","article-title":"Prognosis of seronegative patients in a large prospective cohort of patients with early inflammatory arthritis","volume":"41","author":"Barra","year":"2014","journal-title":"J. Rheumatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.semarthrit.2017.04.009","article-title":"The 2010 ACR\/EULAR criteria are not sufficiently accurate in the early identification of autoantibody-negative rheumatoid arthritis: Results from the Leiden-EAC and ESPOIR cohorts","volume":"47","author":"Boeters","year":"2017","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1136\/annrheumdis-2012-202779","article-title":"EULAR definition of erosive disease in light of the 2010 ACR\/EULAR rheumatoid arthritis classification criteria","volume":"72","author":"Aletaha","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1002\/art.23945","article-title":"An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis","volume":"58","author":"Brown","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"ref_42","first-page":"276","article-title":"Imaging in early rheumatoid arthritis\u2014What is the best method for detecting erosions and disease progression?","volume":"26","author":"Hammer","year":"2014","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5403","DOI":"10.1007\/s00330-025-11493-5","article-title":"Early rheumatoid arthritis, two distinctive structural damage patterns revealed by MRI: An 8-year longitudinal study","volume":"35","author":"Wu","year":"2025","journal-title":"Eur. Radiol."},{"key":"ref_44","first-page":"77","article-title":"A comparative study on the clinical and magnetic resonance imaging features between seronegative and seropositive rheumatoid arthritis","volume":"42","author":"Mo","year":"2024","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"21372","DOI":"10.1038\/s41598-022-25958-w","article-title":"High-frequency ultrasound in patients with seronegative rheumatoid arthritis","volume":"12","author":"Wang","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1002\/jum.16527","article-title":"Contribution of Musculoskeletal Ultrasound in the Diagnosis of Seronegative Rheumatoid Arthritis","volume":"43","author":"Cen","year":"2024","journal-title":"J. Ultrasound Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Xu, J., Gong, Y., Yang, K., Fang, Y., Li, W., and Chen, S. (2024). A cohort study of ultrasonic semi-quantitative scoring for the diagnosis of serology-negative rheumatoid arthritis. Arch. Rheumatol., 39, 579\u2013587.","DOI":"10.46497\/ArchRheumatol.2024.10788"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3899\/jrheum.121313","article-title":"2014 (ESPOIR) Repeated anticitrullinated protein antibody and rheumatoid factor assessment is not necessary in early arthritis","volume":"41","author":"Gossec","year":"2014","journal-title":"J. Rheumatol."},{"key":"ref_49","first-page":"A05190318","article-title":"Use and utility of serologic tests for rheumatoid arthritis in primary care","volume":"67","author":"Tenstad","year":"2020","journal-title":"Dan. Med. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/1756-185X.13000","article-title":"Only rheumatoid factor-positive subset of ACPA-negative RA may seroconvert to ACPA-positive","volume":"20","author":"Hiwa","year":"2017","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1111\/imj.14463","article-title":"Repeat serological testing for ACPAs after diagnosis is not useful","volume":"50","author":"Reid","year":"2020","journal-title":"Intern. Med. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1016\/j.mayocp.2019.05.023","article-title":"Evidence of diagnostic and treatment delay in seronegative rheumatoid arthritis: Missing the window of opportunity","volume":"94","author":"Coffey","year":"2019","journal-title":"Mayo Clin. Proc."},{"key":"ref_53","first-page":"99","article-title":"Prevalence of calcium pyrophosphate deposition disease in a cohort of patients diagnosed with seronegative rheumatoid arthritis","volume":"38","author":"Paalanen","year":"2020","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e002383","DOI":"10.1136\/rmdopen-2022-002383","article-title":"High prevalence of chondrocalcinosis and frequent comorbidity with calcium pyrophosphate deposition disease in patients with seronegative rheumatoid arthritis","volume":"8","author":"Krekeler","year":"2022","journal-title":"RMD Open"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e743","DOI":"10.1016\/S2665-9913(23)00242-4","article-title":"Autoantibody-negative rheumatoid arthritis: Still a challenge for the rheumatologist","volume":"5","author":"Bugatti","year":"2023","journal-title":"Lancet Rheumatol."},{"key":"ref_56","unstructured":"Mahalingam, S., Herrero, L.J., and Herring, B.L. (2021). Viral arthritis. Arthropod Borne Diseases, Springer."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jinf.2023.12.010","article-title":"Diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease: Data from the French Tw-IRD registry","volume":"88","author":"Portillo","year":"2024","journal-title":"J Infect."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1136\/ard.60.11.1021","article-title":"Presenting features of polymyalgia rheumatica (PMR) and rheumatoid arthritis with PMR-like onset: A prospective study","volume":"60","author":"Caporali","year":"2001","journal-title":"Ann. Rheum. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s11882-025-01220-x","article-title":"Lymphoproliferative Disorders Mimicking Rheumatologic Disease: A Clinical Reasoning Perspective","volume":"25","author":"Shen","year":"2025","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"422","DOI":"10.5114\/reum.2022.123672","article-title":"Paraneoplastic arthritides: An up-to-date case-based systematic review","volume":"60","author":"Conticini","year":"2022","journal-title":"Reumatologia"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"rkad041","DOI":"10.1093\/rap\/rkad041","article-title":"First case report of rheumatoid-like paraneoplastic polyarthritis in a patient with Fallopian tube cancer","volume":"7","author":"Lewik","year":"2023","journal-title":"Rheumatol. Adv. Pract."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1136\/annrheumdis-2019-216109","article-title":"Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation","volume":"79","author":"Braaten","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11926-024-01173-6","article-title":"Immune checkpoint inhibitor associated rheumatoid arthritis","volume":"27","author":"Bernabela","year":"2024","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1136\/annrheumdis-2019-216892","article-title":"Response to: Correspondence on \u201cImmune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation\u201d by Braaten et al","volume":"81","author":"Cappelli","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e274","DOI":"10.1016\/S2665-9913(23)00064-4","article-title":"Mortality and immune-related adverse events after immune checkpoint inhibitor initiation for cancer among patients with pre-existing rheumatoid arthritis: A retrospective, comparative cohort study","volume":"5","author":"McCarter","year":"2023","journal-title":"Lancet Rheumatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1007\/s00011-023-01780-6","article-title":"Advances of autoimmune rheumatic diseases related to malignant tumors","volume":"72","author":"Zhao","year":"2023","journal-title":"Inflamm. Res."},{"key":"ref_67","first-page":"e002890","article-title":"Erosive and non-erosive hand osteoarthritis: An update on diagnosis and management","volume":"9","author":"Witthoek","year":"2023","journal-title":"RMD Open"},{"key":"ref_68","first-page":"37","article-title":"Does early seronegative arthritis develop into rheumatoid arthritis? A 10-year observational study","volume":"37","author":"Paalanen","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/nrrheum.2012.153","article-title":"Bone erosion in rheumatoid arthritis: Mechanisms, diagnosis and treatment","volume":"8","author":"Schett","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_70","first-page":"325","article-title":"Mechanisms of bone loss in inflammatory arthritis","volume":"11","author":"Henderson","year":"2015","journal-title":"Nat Rev Rheumatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"728610","DOI":"10.1155\/2015\/728610","article-title":"The role of citrullinated protein antibodies in predicting erosive disease in rheumatoid arthritis: A systematic literature review and meta-analysis","volume":"2015","author":"Jilani","year":"2015","journal-title":"Int. J. Rheumatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1172\/JCI60975","article-title":"Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin","volume":"122","author":"Harre","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_73","first-page":"851","article-title":"Erosion progression in rheumatoid arthritis: Relationship with disease activity and autoantibody status","volume":"72","author":"Aletaha","year":"2013","journal-title":"Ann. Rheum Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s00296-019-04492-5","article-title":"ACPA-positive versus ACPA-negative rheumatoid arthritis: Two distinct erosive disease entities on radiography and ultrasonography","volume":"40","author":"Grosse","year":"2020","journal-title":"Rheumatol. Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1007\/s10067-019-04602-5","article-title":"Differing X-ray patterns in seronegative and seropositive rheumatoid arthritis","volume":"38","author":"Gadeholt","year":"2019","journal-title":"Clin. Rheumatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1093\/rheumatology\/ker129","article-title":"Clinical predictors of erosion-free status in rheumatoid arthritis: A prospective cohort study","volume":"50","author":"Liao","year":"2011","journal-title":"Rheumatology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1002\/acr.22078","article-title":"First-year radiographic progression as a predictor of further progression in early arthritis: Results of a large national French cohort","volume":"65","author":"Saraux","year":"2013","journal-title":"Arthritis Care Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s10067-024-07187-w","article-title":"Are seronegative patients with rheumatoid arthritis and clinically suspect arthralgia properly represented in randomized clinical trials?","volume":"44","author":"Selmi","year":"2025","journal-title":"Clin. Rheumatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1136\/annrheumdis-2014-206047","article-title":"Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: Does a window of opportunity exist? Results on the Leiden Early Arthritis Clinic and ESPOIR cohorts","volume":"74","author":"Tsonaka","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/s41584-025-01289-8","article-title":"The apprehension of seronegative rheumatoid arthritis","volume":"21","author":"Javed","year":"2025","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1136\/annrheumdis-2021-221957","article-title":"Low-dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: The pragmatic randomised, double-blind placebo-controlled GLORIA trial","volume":"81","author":"Boers","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/s13075-019-2020-x","article-title":"Predictors of good response to conventional synthetic DMARDs in early seronegative rheumatoid arthritis: Data from the ESPOIR cohort","volume":"21","author":"Lukas","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13075-022-02851-5","article-title":"Clinical predictors of response to methotrexate in patients with rheumatoid arthritis: A machine learning approach using clinical trial data","volume":"24","author":"Duong","year":"2022","journal-title":"Arthritis Res. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1136\/annrheumdis-2015-207942","article-title":"Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial","volume":"75","author":"Sokolove","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s40744-021-00401-0","article-title":"Baseline anti-citrullinated protein antibody status and response to abatacept or non-TNFi biologic\/targeted synthetic DMARDs: US observational study of patients with RA","volume":"9","author":"Harrold","year":"2022","journal-title":"Rheumatol. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"19717","DOI":"10.1038\/s41598-020-76842-4","article-title":"A retrospective analysis of the relationship between anti-cyclic citrullinated peptide antibody and the effectiveness of abatacept in rheumatoid arthritis patients","volume":"10","author":"Kida","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Lin, C.-T., Huang, W.-N., Tsai, W.-C., Chen, J.P., Wei, J.C.C., and Chen, C.H. (2021). Predictors of drug survival for biologic and targeted synthetic DMARDs in rheumatoid arthritis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0250877"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e000742","DOI":"10.1136\/rmdopen-2018-000742","article-title":"Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in phase III randomized clinical trials of tofacitinib","volume":"5","author":"Bird","year":"2019","journal-title":"RMD Open"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1093\/mr\/roac086","article-title":"Drug-survival profiling of second-line biologic therapy in rheumatoid arthritis: Choice of another tumour necrosis factor inhibitor or a biologic of different mode of action?","volume":"33","author":"Shipa","year":"2023","journal-title":"Mod. Rheumatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/s13075-016-1132-9","article-title":"Sarilumab plus methotrexate suppresses circulating biomarkers of bone resorption and synovial damage in patients with rheumatoid arthritis and inadequate response to methotrexate: A biomarker study of MOBILITY","volume":"18","author":"Boyapati","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_91","unstructured":"Yokota, K., Miyazaki, T., Sato, K., and Tanaka, Y. (2021). TNF- and IL-6-dependent osteoclastogenesis independent of RANKL via activation of NFATc1 and JAK signaling in inflammatory arthritis. Int Immunol., 577\u2013590."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Chung, S.W. (2025). Promising molecular therapeutic targets for drug development in rheumatoid arthritis. J. Clin. Med., 14.","DOI":"10.3390\/jcm14165827"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"333","DOI":"10.2147\/ITT.S288550","article-title":"Bruton\u2019s tyrosine kinase inhibition for the treatment of rheumatoid arthritis","volume":"10","author":"Arneson","year":"2021","journal-title":"ImmunoTargets Ther."}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/1\/14\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T09:03:53Z","timestamp":1766999033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/1\/14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,28]]},"references-count":93,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["medsci14010014"],"URL":"https:\/\/doi.org\/10.3390\/medsci14010014","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,28]]}}}