Abstract
Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, and affects 0.5–1% of the population. Although it poses a considerable health problem, relatively little remains known about the disease pathogenesis and etiology. In the past decade, anti-citrullinated protein antibodies (ACPA) have emerged as suspects in the development and/or progression of RA. Citrullinated proteins—containing the amino acid citrulline, generated post-translationally from arginine—are found in the joints of patients with RA, but are not specific for the disease. This situation contrasts with the presence of ACPA, which are mostly found in individuals with RA. Intriguingly, ACPA can also be found in individuals before symptom onset. In these instances the ACPA response seems to be in its infancy, recognizing only a few citrullinated antigens and not using the full isotype repertoire. These characteristics of the ACPA response mature before clinical disease precipitates. Evidence is emerging that ACPA status can further characterize the heterogeneous RA phenotype, not only with respect to outcome, but perhaps also with respect to intervention. This Review summarizes the evolution of the ACPA response and its putative role in disease pathogenesis, as well as its relationship with clinical phenotype and diagnostic potential.
Key Points
-
The identification of anti-citrullinated protein antibodies (ACPA) has resulted in the identification of a subset of patients with RA with a more homogeneous outcome
-
ACPA are highly specific for RA and can be present years before the first clinical sign of the disease
-
Maturation of the ACPA response is associated with the emergence of clinical symptoms and the transition to RA
-
The presence of ACPA in RA is associated with greater radiological joint damage and with different response to therapy
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Scott, D. L., Wolfe, F. & Huizinga, T. W. Rheumatoid arthritis. Lancet 376, 1094–1108 (2010).
Hassfeld, W. et al. Demonstration of a new antinuclear antibody (anti-RA33) that is highly specific for rheumatoid arthritis. Arthritis Rheum. 32, 1515–1520 (1989).
Skriner, K. et al. Anti-A2/RA33 autoantibodies are directed to the RNA binding region of the A2 protein of the heterogeneous nuclear ribonucleoprotein complex. Differential epitope recognition in rheumatoid arthritis, systemic lupus erythematosus, and mixed connective tissue disease. J. Clin. Invest. 100, 127–135 (1997).
Shi, J. et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc. Natl Acad. Sci. USA 108, 17372–17377 (2011).
Waaler, E. On the occurrence of a factor in human serum activating the specific agglutintion of sheep blood corpuscles. 1939. APMIS 115, 422–438 (2007).
Nienhuis, R. L. & Mandema, E. a new serum factor in patients with rheumatoid arthritis; the antiperinuclear factor. Ann. Rheum. Dis. 23, 302–305 (1964).
Young, B. J., Mallya, R. K., Leslie, R. D., Clark, C. J. & Hamblin, T. J. Anti-keratin antibodies in rheumatoid arthritis. Br. Med. J. 2, 97–99 (1979).
Sebbag, M. et al. The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies. J. Clin. Invest. 95, 2672–2679 (1995).
Aletaha, D. et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann. Rheum. Dis. 69, 1580–1588 (2010).
Aletaha, D. et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 62, 2569–2581 (2010).
Girbal-Neuhauser, E. et al. The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deimination of arginine residues. J. Immunol. 162, 585–594 (1999).
Schellekens, G. A., de Jong, B. A., van den Hoogen, F. H., van de Putte, L. B. & van Venrooij, W. J. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J. Clin. Invest. 101, 273–281 (1998).
Vossenaar, E. R., Zendman, A. J., van Venrooij, W. J. & Pruijn, G. J. PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. Bioessays 25, 1106–1118 (2003).
Schellekens, G. A. et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 43, 155–163 (2000).
Avouac, J., Gossec, L. & Dougados, M. Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann. Rheum. Dis. 65, 845–851 (2006).
Pruijn, G. J., Wiik, A. & van Venrooij, W. J. The use of citrullinated peptides and proteins for the diagnosis of rheumatoid arthritis. Arthritis Res. Ther. 12, 203 (2010).
van Gaalen, F. A. et al. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum. 50, 709–715 (2004).
van Venrooij, W. J., Zendman, A. J. & Pruijn, G. J. Autoantibodies to citrullinated antigens in (early) rheumatoid arthritis. Autoimmun. Rev. 6, 37–41 (2006).
Damjanovska, L. et al. Diagnostic value of anti-MCV antibodies in differentiating early inflammatory arthritis. Ann. Rheum. Dis. 69, 730–732 (2010).
Ioan-Facsinay, A. et al. Anti-cyclic citrullinated peptide antibodies are a collection of anti-citrullinated protein antibodies and contain overlapping and non-overlapping reactivities. Ann. Rheum. Dis. 70, 188–193 (2011).
van Gaalen, F., Ioan-Facsinay, A., Huizinga, T. W. & Toes, R. E. The devil in the details: the emerging role of anticitrulline autoimmunity in rheumatoid arthritis. J. Immunol. 175, 5575–5580 (2005).
van Venrooij, W. J. & Pruijn, G. J. An important step towards completing the rheumatoid arthritis cycle. Arthritis Res. Ther. 10, 117 (2008).
Vossenaar, E. R. & van Venrooij, W. J. Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis. Arthritis Res. Ther. 6, 107–111 (2004).
Cambridge, G. et al. Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum. 48, 2146–2154 (2003).
Edwards, J. C. & Cambridge, G. Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes. Rheumatology (Oxford) 40, 205–211 (2001).
Rantapaa-Dahlqvist, S. et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 48, 2741–2749 (2003).
van de Stadt, L. A. et al. Development of the anti citrullinated peptide antibody repertoire prior to the onset of rheumatoid arthritis. Arthritis Rheum 63, 3226–3233 (2011).
van der Woude, D. et al. Epitope spreading of the anti-citrullinated protein antibody response occurs before disease onset and is associated with the disease course of early arthritis. Ann. Rheum. Dis. 69, 1554–1561 (2010).
van Oosterhout, M. et al. Differences in synovial tissue infiltrates between anti-cyclic citrullinated peptide-positive rheumatoid arthritis and anti-cyclic citrullinated peptide-negative rheumatoid arthritis. Arthritis Rheum. 58, 53–60 (2008).
Nielen, M. M. et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 50, 380–386 (2004).
Imafuku, Y., Yoshida, H. & Yamada, Y. Reactivity of agalactosyl IgG with rheumatoid factor. Clin. Chim. Acta 334, 217–223 (2003).
Scherer, H. U. et al. Glycan profiling of anti-citrullinated protein antibodies isolated from human serum and synovial fluid. Arthritis Rheum. 62, 1620–1629 (2010).
Ioan-Facsinay, A. et al. Marked differences in fine specificity and isotype usage of the anti-citrullinated protein antibody in health and disease. Arthritis Rheum. 58, 3000–3008 (2008).
Daha, N. A. et al. Complement activation by (auto-) antibodies. Mol. Immunol. 48, 1656–1665 (2011).
Nimmerjahn, F. & Ravetch, J. V. Fcγ receptors as regulators of immune responses. Nat. Rev. Immunol. 8, 34–47 (2008).
Sjoberg, A. P., Trouw, L. A. & Blom, A. M. Complement activation and inhibition: a delicate balance. Trends Immunol. 30, 83–90 (2009).
Trouw, L. A. et al. Anti-cyclic citrullinated peptide antibodies from rheumatoid arthritis patients activate complement via both the classical and alternative pathways. Arthritis Rheum. 60, 1923–1931 (2009).
Banda, N. K., Takahashi, K., Wood, A. K., Holers, V. M. & Arend, W. P. Pathogenic complement activation in collagen antibody-induced arthritis in mice requires amplification by the alternative pathway. J. Immunol. 179, 4101–4109 (2007).
Clavel, C. et al. Induction of macrophage secretion of tumor necrosis factor α through Fcγ receptor IIa engagement by rheumatoid arthritis-specific autoantibodies to citrullinated proteins complexed with fibrinogen. Arthritis Rheum. 58, 678–688 (2008).
Schuerwegh, A. J. et al. Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis. Proc. Natl Acad. Sci. USA 107, 2586–2591 (2010).
Duplan, V. et al. In the rat, citrullinated autologous fibrinogen is immunogenic but the induced autoimmune response is not arthritogenic. Clin. Exp. Immunol. 145, 502–512 (2006).
Kuhn, K. A. et al. Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis. J. Clin. Invest. 116, 961–973 (2006).
Lundberg, K. et al. Citrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity. Arthritis Res. Ther. 7, R458–R467 (2005).
Uysal, H. et al. Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis. J. Exp. Med. 206, 449–462 (2009).
Snir, O. et al. Multiple antibody reactivities to citrullinated antigens in sera from rheumatoid arthritis patients—association with HLA-DRB1 alleles. Ann. Rheum. Dis. 68, 736–743 (2009).
Takizawa, Y. et al. Citrullinated fibrinogen detected as a soluble citrullinated autoantigen in rheumatoid arthritis synovial fluids. Ann. Rheum. Dis. 65, 1013–1020 (2006).
Masson-Bessiere, C. et al. The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the α- and β-chains of fibrin. J. Immunol. 166, 4177–4184 (2001).
Vossenaar, E. R. et al. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthritis Res. Ther. 6, R142–R150 (2004).
Koivula, M. K. et al. Autoantibodies binding to citrullinated telopeptide of type II collagen and to cyclic citrullinated peptides predict synergistically the development of seropositive rheumatoid arthritis. Ann. Rheum. Dis. 66, 1450–1455 (2007).
Kinloch, A. et al. Identification of citrullinated α-enolase as a candidate autoantigen in rheumatoid arthritis. Arthritis Res. Ther. 7, R1421–R1429 (2005).
Arbuckle, M. R. et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N. Engl. J. Med. 349, 1526–1533 (2003).
Rock, B. et al. The pathogenic effect of IgG4 autoantibodies in endemic pemphigus foliaceus (fogo selvagem). N. Engl. J. Med. 320, 1463–1469 (1989).
Amagai, M., Tsunoda, K., Zillikens, D., Nagai, T. & Nishikawa, T. The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile. J. Am. Acad. Dermatol. 40, 167–170 (1999).
Li, N., Aoki, V., Hans-Filho, G., Rivitti, E. A. & Diaz, L. A. The role of intramolecular epitope spreading in the pathogenesis of endemic pemphigus foliaceus (fogo selvagem). J. Exp. Med. 197, 1501–1510 (2003).
Bos, W. H. et al. Arthritis development in patients with arthralgia is strongly associated with anti-citrullinated protein antibody status: a prospective cohort study. Ann. Rheum. Dis. 69, 490–494 (2010).
van de Stadt, L. A. et al. The extent of the anti-citrullinated protein antibody repertoire is associated with arthritis development in patients with seropositive arthralgia. Ann. Rheum. Dis. 70, 128–133 (2011).
Verpoort, K. N. et al. Isotype distribution of anti-cyclic citrullinated peptide antibodies in undifferentiated arthritis and rheumatoid arthritis reflects an ongoing immune response. Arthritis Rheum. 54, 3799–3808 (2006).
Kokkonen, H. et al. Antibodies of IgG, IgA and IgM isotypes against cyclic citrullinated peptide precede the development of rheumatoid arthritis. Arthritis Res. Ther. 13, R13 (2011).
Villalta, D. et al. Anti-dsDNA antibody avidity determination by a simple reliable ELISA method for SLE diagnosis and monitoring. Lupus 12, 31–36 (2003).
Cucnik, S., Kveder, T., Krizaj, I., Rozman, B. & Bozic, B. High avidity anti-β 2-glycoprotein I antibodies in patients with antiphospholipid syndrome. Ann. Rheum. Dis. 63, 1478–1482 (2004).
Westerlund, A. et al. Absence of avidity maturation of autoantibodies to the protein tyrosine phosphatase-like IA-2 molecule and glutamic acid decarboxylase (GAD65) during progression to type 1 diabetes. J. Autoimmun. 24, 153–167 (2005).
Suwannalai, P. et al. Anti-citrullinated protein antibodies have a low avidity compared with antibodies against recall antigens. Ann. Rheum. Dis. 70, 373–379 (2011).
Huang, H., Benoist, C. & Mathis, D. Rituximab specifically depletes short-lived autoreactive plasma cells in a mouse model of inflammatory arthritis. Proc. Natl Acad. Sci. USA 107, 4658–4663 (2010).
Vora, K. A. et al. Cutting edge: germinal centers formed in the absence of B cell-activating factor belonging to the TNF family exhibit impaired maturation and function. J. Immunol. 171, 547–551 (2003).
Storey, G. D. Alfred Baring Garrod (1819–1907). Rheumatology (Oxford) 40, 1189–1190 (2001).
Bennett, G. A., Cobb, S., Jacox, R., Jessar, R. A. & Ropes, M. W. Proposed diagnostic criteria for rheumatoid arthritis. Bull. Rheum. Dis. 7, 121–124 (1956).
Kellgren, J. H. The university centre for the study of chronic rheumatism. Manch. Med. Gaz. 42, 4–7 (1962).
Bennett, P. D. & Burch, T. A. New York symposium on population studies in the rheumatic diseases. A new diagnostic criteria. Bull. Rheum. Dis. 17, 453–458 (1967).
Arnett, F. C. et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 31, 315–324 (1988).
van Venrooij, W. J., van Beers, J. J. & Pruijn, G. J. Anti-CCP antibody, a marker for the early detection of rheumatoid arthritis. Ann. NY Acad. Sci. 1143, 268–285 (2008).
Huizinga, T. W. et al. Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins. Arthritis Rheum. 52, 3433–3438 (2005).
Klareskog, L. et al. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum. 54, 38–46 (2006).
Linn-Rasker, S. P. et al. Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann. Rheum. Dis. 65, 366–371 (2006).
Verpoort, K. N. et al. Association of HLA-DR3 with anti-cyclic citrullinated peptide antibody-negative rheumatoid arthritis. Arthritis Rheum. 52, 3058–3062 (2005).
Irigoyen, P. et al. Regulation of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: contrasting effects of HLA-DR3 and the shared epitope alleles. Arthritis Rheum. 52, 3813–3818 (2005).
Mahdi, H. et al. Specific interaction between genotype, smoking and autoimmunity to citrullinated α-enolase in the etiology of rheumatoid arthritis. Nat. Genet. 41, 1319–1324 (2009).
van der Woude, D. et al. Gene–environment interaction influences the reactivity of autoantibodies to citrullinated antigens in rheumatoid arthritis. Nat. Genet. 42, 814–816 (2010).
Willemze, A. et al. The interaction between HLA shared epitope alleles and smoking and its contribution to autoimmunity against several citrullinated antigens. Arthritis Rheum. 63, 1823–1832 (2011).
Verpoort, K. N. et al. Fine specificity of the anti-citrullinated protein antibody response is influenced by the shared epitope alleles. Arthritis Rheum. 56, 3949–3952 (2007).
Willemze, A. et al. The ACPA recognition profile and subgrouping of ACPA-positive RA patients. Ann. Rheum. Dis. http://dx.doi.org/10.1136/annrheumdis-2011-200421.
van Dongen, H. et al. Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 56, 1424–1432 (2007).
Visser, K. et al. Pretreatment serum levels of anti-cyclic citrullinated peptide antibodies are associated with the response to methotrexate in recent-onset arthritis. Ann. Rheum. Dis. 67, 1194–1195 (2008).
Visser, K. et al. A matrix risk model for the prediction of rapid radiographic progression in patients with rheumatoid arthritis receiving different dynamic treatment strategies: post hoc analyses from the BeSt study. Ann. Rheum. Dis. 69, 1333–1337 (2010).
Sellam, J. et al. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum. 63, 933–938 (2011).
Majka, D. S. & Holers, V. M. Can we accurately predict the development of rheumatoid arthritis in the preclinical phase? Arthritis Rheum. 48, 2701–2705 (2003).
Green, M. et al. Persistence of mild, early inflammatory arthritis: the importance of disease duration, rheumatoid factor, and the shared epitope. Arthritis Rheum. 42, 2184–2188 (1999).
Mottonen, T. et al. Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis. Arthritis Rheum. 46, 894–898 (2002).
Nell, V. P. et al. Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford) 43, 906–914 (2004).
van der Linden, M. P. et al. Long-term impact of delay in assessment of early arthritis patients. Arthritis Rheum. 62, 3537–3546 (2010).
Willemze, A. et al. The window of opportunity in ACPA-positive rheumatoid arthritis is not explained by ACPA characteristics. Ann. Rheum. Dis. 70, 1697–1698 (2011).
van der Woude, D. et al. Prevalence of and predictive factors for sustained disease-modifying antirheumatic drug-free remission in rheumatoid arthritis: results from two large early arthritis cohorts. Arthritis Rheum. 60, 2262–2271 (2009).
Ursum, J., Bos, W. H., van, D. N., Dijkmans, B. A. & van, S. D. Levels of anti-citrullinated protein antibodies and IgM rheumatoid factor are not associated with outcome in early arthritis patients: a cohort study. Arthritis Res. Ther. 12, R8 (2010).
van Venrooij, W. J., van Beers, J. J. & Pruijn, G. J. Anti-CCP antibodies: the past, the present and the future. Nat. Rev. Rheumatol. 7, 391–398 (2011).
Nishimura, K. et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann. Intern. Med. 146, 797–808 (2007).
Cader, M. Z., Filer, A. D., Buckley, C. D. & Raza, K. The relationship between the presence of anti-cyclic citrullinated peptide antibodies and clinical phenotype in very early rheumatoid arthritis. BMC Musculoskelet. Disord. 11, 187 (2010).
van der Helm-van Mil AH, Verpoort, K. N., Breedveld, F. C., Toes, R. E. & Huizinga, T. W. Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res. Ther. 7, R949–R958 (2005).
Lopez-Longo, F. J., Sanchez-Ramon, S. & Carreno, L. The value of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: do they imply new risk factors? Drug News Perspect. 22, 543–548 (2009).
Aubart, F. et al. High levels of anti-cyclic citrullinated peptide autoantibodies are associated with co-occurrence of pulmonary diseases with rheumatoid arthritis. J. Rheumatol. 38, 979–982 (2011).
Jansen, L. M. et al. The predictive value of anti-cyclic citrullinated peptide antibodies in early arthritis. J. Rheumatol. 30, 1691–1695 (2003).
Kroot, E. J. et al. The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 43, 1831–1835 (2000).
Syversen, S. W. et al. High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann. Rheum. Dis. 67, 212–217 (2008).
Machold, K. P. et al. Very recent onset rheumatoid arthritis: clinical and serological patient characteristics associated with radiographic progression over the first years of disease. Rheumatology (Oxford) 46, 342–349 (2007).
de Vries-Bouwstra, J. K. et al. Progression of joint damage in early rheumatoid arthritis: association with HLA-DRB1, rheumatoid factor, and anti-citrullinated protein antibodies in relation to different treatment strategies. Arthritis Rheum. 58, 1293–1298 (2008).
Fisher, B. A. et al. Antibodies to citrullinated α-enolase peptide 1 and clinical and radiological outcomes in rheumatoid arthritis. Ann. Rheum. Dis. 70, 1095–1098 (2011).
Scherer, H. U. et al. Distinct ACPA fine specificities, formed under the influence of HLA shared epitope alleles, have no effect on radiographic joint damage in rheumatoid arthritis. Ann. Rheum. Dis. 70, 1461–1464 (2011).
van der Woude, D. et al. The ACPA isotype profile reflects long-term radiographic progression in rheumatoid arthritis. Ann. Rheum. Dis. 69, 1110–1116 (2010).
Author information
Authors and Affiliations
Contributions
All authors contributed equally to researching data for the article, writing the article, discussions of the content, and review and/or editing of the manuscript before submission.
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Willemze, A., Trouw, L., Toes, R. et al. The influence of ACPA status and characteristics on the course of RA. Nat Rev Rheumatol 8, 144–152 (2012). https://doi.org/10.1038/nrrheum.2011.204
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrrheum.2011.204
This article is cited by
-
Prodrug-based nanomedicines for rheumatoid arthritis
Discover Nano (2024)
-
Clinical significance of anti-cyclic citrullinated peptide (anti-CCP) antibodies in rheumatoid arthritis: Literature review
SN Comprehensive Clinical Medicine (2023)
-
From risk to chronicity: evolution of autoreactive B cell and antibody responses in rheumatoid arthritis
Nature Reviews Rheumatology (2022)
-
The current status of anti-citrullinated protein antibodies and citrullinated protein-reactive B cells in the pathogenesis of rheumatoid arthritis
Molecular Biology Reports (2022)
-
Evaluating the Similarity of Different Collagen-Induced Arthritis Models to the Pre-Clinical Phase of RA in Female Rats
Inflammation (2022)