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Rheumatology International
Published in: Rheumatology International 8/2016

01-08-2016 | Biomarkers

Anti-citrullinated peptide antibodies and their value for predicting responses to biologic agents: a review

Authors: Emilio Martin-Mola, Alejandro Balsa, Rosario García-Vicuna, Juan Gómez-Reino, Miguel Angel González-Gay, Raimon Sanmartí, Estíbaliz Loza

Published in: Rheumatology International | Issue 8/2016

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Abstract

Anti-citrullinated peptide antibodies (ACPAs) play an important pathogenic role both at the onset and during the disease course. These antibodies precede the clinical appearance of rheumatoid arthritis (RA) and are associated with a less favorable prognosis, both clinically and radiologically. The objective of this work was to conduct a comprehensive review of studies published through September 2015 of ACPAs’ role as a predictor of the therapeutic response to the biological agents in RA patients. The review also includes summary of the biology and detection of ACPAs as well as ACPAs in relation to joint disease and CV disease and the possible role of seroconversion. The reviews of studies examining TNF inhibitors and tocilizumab yielded negative results. In the case of rituximab, the data indicated a greater probability of clinical benefit in ACPA+ patients versus ACPA− patients, as has been previously described for rheumatoid factor. Nonetheless, the effect is discreet and heterogeneous. Another drug that may have greater effectiveness in ACPA+ patients is abatacept. Some studies have suggested that the drug is more efficient in ACPA+ patients and that those patients show greater drug retention. In a subanalysis of the AMPLE trial, patients with very high ACPA titers who were treated with abatacept had a statistically significant response compared to patients with lower titers. In summary, the available studies suggest that the presence of or high titers of ACPA may predict a better response to rituximab and/or abatacept. Evidence regarding TNFi and tocilizumab is lacking. However, there is a lack of studies with appropriate designs to demonstrate that some drugs are superior to others for ACPA+ patients.
Literature
1.
Carmona L, Villaverde V, Hernandez-Garcia C, Ballina J, Gabriel R, Laffon A (2002) The prevalence of rheumatoid arthritis in the general population of Spain. Rheumatology 41(1):88–95PubMedCrossRef
2.
3.
Klareskog L, Amara K, Malmstrom V (2014) Adaptive immunity in rheumatoid arthritis: anticitrulline and other antibodies in the pathogenesis of rheumatoid arthritis. Curr Opin Rheumatol 26(1):72–79PubMedCrossRef
4.
van Gaalen F, Ioan-Facsinay A, Huizinga TW, Toes RE (2005) The devil in the details: the emerging role of anticitrulline autoimmunity in rheumatoid arthritis. J Immunol 175(9):5575–5580PubMedCrossRef
5.
van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW (2005) Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther 7(5):R949–R958PubMedPubMedCentralCrossRef
6.
Lopez-Longo FJ, Oliver-Minarro D, de la Torre I, Gonzalez-Diaz de Rabago E, Sanchez-Ramon S, Rodriguez-Mahou M et al (2009) Association between anti-cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis. Arthritis Rheum 61(4):419–424PubMedCrossRef
7.
Zhu J, Zhou Y, Chen X, Li J (2014) A metaanalysis of the increased risk of rheumatoid arthritis-related pulmonary disease as a result of serum anticitrullinated protein antibody positivity. J Rheumatol 41(7):1282–1289PubMedCrossRef
8.
Isaacs JD, Cohen SB, Emery P, Tak PP, Wang J, Lei G et al (2013) Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis. Ann Rheum Dis 72(3):329–336PubMedCrossRef
9.
de Lemos LL, Costa Jde O, Machado MA, Almeida AM, Barbosa MM, Kakehasi AM et al (2014) Rituximab for rheumatoid arthrits treatment: a systematic review. Rev Bras Reumatol 54(3):220–230PubMedCrossRef
10.
Huizinga TWJ, Connolly SE, Johnsen A, Zhu J, Furst DE, Bykerk VP et al (2015) Effect of anti-cyclic citrullinated peptide 2 immunoglobulin M serostatus on efficacy outcomes following treatment with abatacept plus methotrexate in the AVERT trial. Ann Rheum Dis 74(Suppl2):234–235PubMed
11.
Gottenberg JE, Neto D, Gomez-Reino J, Iannone F, Lie E, Canhão H et al (2014) Positivity for rheumatoid factor and anti-cyclic citrullinated peptide is associated with a better drug retention of abatacept: data from a paneuropean analysis of RA registries. Ann Rheum Dis 73(suppl2):502–503
12.
Sokolove J, Schiff M, Fleischmann R, Weinblatt ME, Connolly SE, Johnsen A, et al (2016) 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. Ann Rheum Dis 75(4):709–714PubMedCrossRef
13.
van Boekel MA, Vossenaar ER, van den Hoogen FH, van Venrooij WJ (2002) Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Res 4(2):87–93PubMedCrossRef
14.
15.
16.
Sebbag M, Simon M, Vincent C, Masson-Bessiere C, Girbal E, Durieux JJ et al (1995) The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies. J Clin Invest 95(6):2672–2679PubMedPubMedCentralCrossRef
17.
Munoz-Fernandez S, Alvarez-Doforno R, Cuesta M, Balsa A, Fontan G, Gijon-Banos J (1995) Antiperinuclear factor: a useful test for the diagnosis of rheumatoid arthritis. Rheumatol Int 15(4):145–149PubMedCrossRef
18.
Munoz-Fernandez S, Alvarez-Doforno R, Gonzalez-Tarrio JM, Balsa A, Richi P, Fontan G et al (1999) Antiperinuclear factor as a prognostic marker in rheumatoid arthritis. J Rheumatol 26(12):2572–2577PubMed
19.
Vincent C, de Keyser F, Masson-Bessiere C, Sebbag M, Veys EM, Serre G (1999) Anti-perinuclear factor compared with the so called “antikeratin” antibodies and antibodies to human epidermis filaggrin, in the diagnosis of arthritides. Ann Rheum Dis 58(1):42–48PubMedPubMedCentralCrossRef
20.
Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ (1998) Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 101(1):273–281PubMedPubMedCentralCrossRef
21.
Girbal-Neuhauser E, Durieux JJ, Arnaud M, Dalbon P, Sebbag M, Vincent C et al (1999) 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(1):585–594PubMed
22.
Nogueira L, Sebbag M, Vincent C, Arnaud M, Fournie B, Cantagrel A et al (2001) Performance of two ELISAs for antifilaggrin autoantibodies, using either affinity purified or deiminated recombinant human filaggrin, in the diagnosis of rheumatoid arthritis. Ann Rheum Dis 60(9):882–887PubMedPubMedCentral
23.
Vincent C, Nogueira L, Sebbag M, Chapuy-Regaud S, Arnaud M, Letourneur O et al (2002) Detection of antibodies to deiminated recombinant rat filaggrin by enzyme-linked immunosorbent assay: a highly effective test for the diagnosis of rheumatoid arthritis. Arthritis Rheum 46(8):2051–2058PubMedCrossRef
24.
Schellekens GA, Visser H, de Jong BA, van den Hoogen FH, Hazes JM, Breedveld FC et al (2000) The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43(1):155–163PubMedCrossRef
25.
Zendman AJ, van Venrooij WJ, Pruijn GJ (2006) Use and significance of anti-CCP autoantibodies in rheumatoid arthritis. Rheumatology 45(1):20–25PubMedCrossRef
26.
Damjanovska L, Thabet MM, Levarth EW, Stoeken-Rijsbergen G, van der Voort EI, Toes RE et al (2010) Diagnostic value of anti-MCV antibodies in differentiating early inflammatory arthritis. Ann Rheum Dis 69(4):730–732PubMedCrossRef
27.
Sanmarti R, Graell E, Perez ML, Ercilla G, Vinas O, Gomez-Puerta JA et al (2009) Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis. Arthritis Res Ther 11(5):R135PubMedPubMedCentralCrossRef
28.
Ioan-Facsinay A, el-Bannoudi H, Scherer HU, van der Woude D, Menard HA, Lora M et al (2011) Anti-cyclic citrullinated peptide antibodies are a collection of anti-citrullinated protein antibodies and contain overlapping and non-overlapping reactivities. Ann Rheum Dis 70(1):188–193PubMedCrossRef
29.
Willemze A, Trouw LA, Toes RE, Huizinga TW (2012) The influence of ACPA status and characteristics on the course of RA. Nat Rev Rheumatol 8(3):144–152PubMedCrossRef
30.
Shi J, Willemze A, Janssen GM, van Veelen PA, Drijfhout JW, Cerami A et al (2013) Recognition of citrullinated and carbamylated proteins by human antibodies: specificity, cross-reactivity and the ‘AMC-Senshu’ method. Ann Rheum Dis 72(1):148–150PubMedCrossRef
31.
Vossenaar ER, Zendman AJ, van Venrooij WJ, Pruijn GJ (2003) PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. BioEssays 25(11):1106–1118PubMedCrossRef
32.
Asaga H, Yamada M, Senshu T (1998) Selective deimination of vimentin in calcium ionophore-induced apoptosis of mouse peritoneal macrophages. Biochem Biophys Res Commun 243(3):641–646PubMedCrossRef
33.
Masson-Bessiere C, Sebbag M, Girbal-Neuhauser E, Nogueira L, Vincent C, Senshu T et al (2001) The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the alpha- and beta-chains of fibrin. J Immunol 166(6):4177–4184PubMedCrossRef
34.
Vossenaar ER, Despres N, Lapointe E, van der Heijden A, Lora M, Senshu T et al (2004) Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthritis Res Ther 6(2):R142–R150PubMedPubMedCentralCrossRef
35.
Vossenaar ER, Nijenhuis S, Helsen MM, van der Heijden A, Senshu T, van den Berg WB et al (2003) Citrullination of synovial proteins in murine models of rheumatoid arthritis. Arthritis Rheum 48(9):2489–2500PubMedCrossRef
36.
Vossenaar ER, Smeets TJ, Kraan MC, Raats JM, van Venrooij WJ, Tak PP (2004) The presence of citrullinated proteins is not specific for rheumatoid synovial tissue. Arthritis Rheum 50(11):3485–3494PubMedCrossRef
37.
De Rycke L, Nicholas AP, Cantaert T, Kruithof E, Echols JD, Vandekerckhove B et al (2005) Synovial intracellular citrullinated proteins colocalizing with peptidyl arginine deiminase as pathophysiologically relevant antigenic determinants of rheumatoid arthritis-specific humoral autoimmunity. Arthritis Rheum 52(8):2323–2330PubMedCrossRef
38.
Wegner N, Wait R, Sroka A, Eick S, Nguyen KA, Lundberg K et al (2010) Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and alpha-enolase: implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum 62(9):2662–2672PubMedPubMedCentralCrossRef
39.
Avouac J, Gossec L, Dougados M (2006) Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis 65(7):845–851PubMedPubMedCentralCrossRef
40.
Riedemann JP, Munoz S, Kavanaugh A (2005) The use of second generation anti-CCP antibody (anti-CCP2) testing in rheumatoid arthritis—a systematic review. Clin Exp Rheumatol 23(5 Suppl 39):S69–S76PubMed
41.
Edwards JC, Leandro MJ, Cambridge G (2005) B lymphocyte depletion in rheumatoid arthritis: targeting of CD20. Curr Dir Autoimmun 8:175–192PubMedCrossRef
42.
Kuhn KA, Kulik L, Tomooka B, Braschler KJ, Arend WP, Robinson WH et al (2006) Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis. J Clin Invest 116(4):961–973PubMedPubMedCentralCrossRef
43.
Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH et al (2004) Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 50(2):380–386PubMedCrossRef
44.
Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H et al (2003) Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 48(10):2741–2749PubMedCrossRef
45.
Berglin E, Padyukov L, Sundin U, Hallmans G, Stenlund H, Van Venrooij WJ et al (2004) A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis. Arthritis Res Ther 6(4):R303–R308PubMedPubMedCentralCrossRef
46.
Ronnelid J, Wick MC, Lampa J, Lindblad S, Nordmark B, Klareskog L et al (2005) 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. Ann Rheum Dis 64(12):1744–1749PubMedPubMedCentralCrossRef
47.
Sokolove J, Bromberg R, Deane KD, Lahey LJ, Derber LA, Chandra PE et al (2012) Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS One 7(5):e35296PubMedPubMedCentralCrossRef
48.
Brink M, Hansson M, Mathsson L, Jakobsson PJ, Holmdahl R, Hallmans G et al (2013) Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis. Arthritis Rheum 65(4):899–910PubMedCrossRef
49.
van de Stadt LA, Witte BI, Bos WH, van Schaardenburg D (2013) A prediction rule for the development of arthritis in seropositive arthralgia patients. Ann Rheum Dis 72(12):1920–1926PubMedCrossRef
50.
de Hair MJ, Landewe RB, van de Sande MG, van Schaardenburg D, van Baarsen LG, Gerlag DM et al (2013) Smoking and overweight determine the likelihood of developing rheumatoid arthritis. Ann Rheum Dis 72(10):1654–1658PubMedCrossRef
51.
Gregersen PK, Silver J, Winchester RJ (1987) The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 30(11):1205–1213PubMedCrossRef
52.
Balsa A, Cabezon A, Orozco G, Cobo T, Miranda-Carus E, Lopez-Nevot MA et al (2010) Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regulation of antibodies against citrullinated proteins and rheumatoid factor. Arthritis Res Ther 12(2):R62PubMedPubMedCentralCrossRef
53.
Zanelli E, Breedveld FC, de Vries RR (2000) HLA class II association with rheumatoid arthritis: facts and interpretations. Hum Immunol 61(12):1254–1261PubMedCrossRef
54.
Hill J, Cairns E, Bell DA (2004) The joy of citrulline: new insights into the diagnosis, pathogenesis, and treatment of rheumatoid arthritis. J Rheumatol 31(8):1471–1473PubMed
55.
Huizinga TW, Amos CI, van der Helm-van Mil AH, Chen W, van Gaalen FA, Jawaheer D et al (2005) Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins. Arthritis Rheum 52(11):3433–3438PubMedCrossRef
56.
Irigoyen P, Lee AT, Wener MH, Li W, Kern M, Batliwalla F et al (2005) Regulation of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: contrasting effects of HLA-DR3 and the shared epitope alleles. Arthritis Rheum 52(12):3813–3818PubMedCrossRef
57.
Aarden LA, Helle M, Boeije L, Pascual-Salcedo D, de Groot E (1991) Differential induction of interleukin-6 production in monocytes, endothelial cells and smooth muscle cells. In: Bienvenu J, Fradezeli D (eds) Cytokines and inflammation. John Libbey Eurotext, Paris, pp 15–27
58.
Klareskog L, Stolt P, Lundberg K, Kallberg H, Bengtsson C, Grunewald J et al (2006) 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(1):38–46PubMedCrossRef
59.
Klareskog L, Padyukov L, Ronnelid J, Alfredsson L (2006) Genes, environment and immunity in the development of rheumatoid arthritis. Curr Opin Immunol 18(6):650–655PubMedCrossRef
60.
Scher JU, Bretz WA, Abramson SB (2014) Periodontal disease and subgingival microbiota as contributors for rheumatoid arthritis pathogenesis: modifiable risk factors? Curr Opin Rheumatol 26(4):424–429PubMedPubMedCentralCrossRef
61.
Gomez-Reino Carnota JJ, Maceiras Pan F (2000) Genetics of rheumatoid arthritis. Med Clin 114(1):16–18CrossRef
62.
Plenge RM, Padyukov L, Remmers EF, Purcell S, Lee AT, Karlson EW et al (2005) Replication of putative candidate-gene associations with rheumatoid arthritis in >4000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4. Am J Hum Genet 77(6):1044–1060PubMedPubMedCentralCrossRef
63.
Orozco G, Sanchez E, Gonzalez-Gay MA, Lopez-Nevot MA, Torres B, Caliz R et al (2005) Association of a functional single-nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Rheum 52(1):219–224PubMedCrossRef
64.
Johansson M, Arlestig L, Hallmans G, Rantapaa-Dahlqvist S (2006) PTPN22 polymorphism and anti-cyclic citrullinated peptide antibodies in combination strongly predicts future onset of rheumatoid arthritis and has a specificity of 100% for the disease. Arthritis Res Ther 8(1):R19PubMedCrossRef
65.
Vossenaar ER, van Venrooij WJ (2004) Anti-CCP antibodies, a highly specific marker for (early) rheumatoid arthritis. Clin Appl Immunol Rev 4:239–262CrossRef
66.
Whiting PF, Smidt N, Sterne JA, Harbord R, Burton A, Burke M et al (2010) Systematic review: accuracy of anti-citrullinated Peptide antibodies for diagnosing rheumatoid arthritis. Ann Intern Med. 152(7):456–464 W155-66 PubMedCrossRef
67.
van Oosterhout M, Bajema I, Levarht EW, Toes RE, Huizinga TW, van Laar JM (2008) Differences in synovial tissue infiltrates between anti-cyclic citrullinated peptide-positive rheumatoid arthritis and anti-cyclic citrullinated peptide-negative rheumatoid arthritis. Arthritis Rheum 58(1):53–60PubMedCrossRef
68.
De Rycke L, Peene I, Hoffman IE, Kruithof E, Union A, Meheus L et al (2004) Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations. Ann Rheum Dis 63(12):1587–1593PubMedPubMedCentralCrossRef
69.
Jansen LM, van Schaardenburg D, van der Horst-Bruinsma I, van der Stadt RJ, de Koning MH, Dijkmans BA (2003) The predictive value of anti-cyclic citrullinated peptide antibodies in early arthritis. J Rheumatol 30(8):1691–1695PubMed
70.
Syversen SW, Gaarder PI, Goll GL, Odegard S, Haavardsholm EA, Mowinckel P et al (2008) 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(2):212–217PubMedCrossRef
71.
Machold KP, Stamm TA, Nell VP, Pflugbeil S, Aletaha D, Steiner G et al (2007) Very recent onset rheumatoid arthritis: clinical and serological patient characteristics associated with radiographic progression over the first years of disease. Rheumatology 46(2):342–349PubMedCrossRef
72.
Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM et al (2005) Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 52(11):3381–3390PubMedCrossRef
73.
de Vries-Bouwstra JK, Goekoop-Ruiterman YP, Verpoort KN, Schreuder GM, Ewals JA, Terwiel JP et al (2008) 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(5):1293–1298PubMedCrossRef
74.
Berglin E, Johansson T, Sundin U, Jidell E, Wadell G, Hallmans G et al (2006) Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset. Ann Rheum Dis 65(4):453–458PubMedCrossRef
75.
Forslind K, Ahlmen M, Eberhardt K, Hafstrom I, Svensson B (2004) Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Ann Rheum Dis 63(9):1090–1095PubMedPubMedCentralCrossRef
76.
Hecht C, Englbrecht M, Rech J, Schmidt S, Araujo E, Engelke K et al (2015) Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on bone erosions in patients with RA. Ann Rheum Dis 74(12):2151–2156PubMedCrossRef
77.
Kroot EJ, de Jong BA, van Leeuwen MA, Swinkels H, van den Hoogen FH, van’t Hof M et al (2000) The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum 43(8):1831–1835PubMedCrossRef
78.
van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, de Jong BA, Breedveld FC, Verweij CL et al (2004) Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum 50(3):709–715PubMedCrossRef
79.
Meyer O, Labarre C, Dougados M, Goupille P, Cantagrel A, Dubois A et al (2003) Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage. Ann Rheum Dis 62(2):120–126PubMedPubMedCentralCrossRef
80.
Cui J, Saevarsdottir S, Thomson B, Padyukov L, van der Helm-van Mil AH, Nititham J et al (2010) Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy. Arthritis Rheum 62(7):1849–1861PubMedPubMedCentral
81.
Guler H, Turhanoglu AD, Ozer B, Ozer C, Balci A (2008) The relationship between anti-cyclic citrullinated peptide and bone mineral density and radiographic damage in patients with rheumatoid arthritis. Scand J Rheumatol 37(5):337–342PubMedCrossRef
82.
Boyesen P, Hoff M, Odegard S, Haugeberg G, Syversen SW, Gaarder PI et al (2009) Antibodies to cyclic citrullinated protein and erythrocyte sedimentation rate predict hand bone loss in patients with rheumatoid arthritis of short duration: a longitudinal study. Arthritis Res Ther 11(4):R103PubMedPubMedCentralCrossRef
83.
Kleyer A, Finzel S, Rech J, Manger B, Krieter M, Faustini F et al (2014) Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies. Ann Rheum Dis 73(5):854–860PubMedCrossRef
84.
Harre U, Georgess D, Bang H, Bozec A, Axmann R, Ossipova E et al (2012) Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest 122(5):1791–1802PubMedPubMedCentralCrossRef
85.
Kleyer A, Schett G (2014) Arthritis and bone loss: a hen and egg story. Curr Opin Rheumatol 26(1):80–84PubMedCrossRef
86.
Goodson N, Marks J, Lunt M, Symmons D (2005) Cardiovascular admissions and mortality in an inception cohort of patients with rheumatoid arthritis with onset in the 1980s and 1990s. Ann Rheum Dis 64(11):1595–1601PubMedPubMedCentralCrossRef
87.
Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE et al (2003) Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 107(9):1303–1307PubMedCrossRef
88.
Avina-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D (2008) Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 59(12):1690–1697PubMedCrossRef
89.
Zinger H, Sherer Y, Shoenfeld Y (2009) Atherosclerosis in autoimmune rheumatic diseases-mechanisms and clinical findings. Clin Rev Allergy Immunol 37(1):20–28PubMedCrossRef
90.
Gonzalez-Gay MA, Gonzalez-Juanatey C, Martin J (2005) Rheumatoid arthritis: a disease associated with accelerated atherogenesis. Semin Arthritis Rheum 35(1):8–17PubMedCrossRef
91.
Shoenfeld Y, Gerli R, Doria A, Matsuura E, Cerinic MM, Ronda N et al (2005) Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation 112(21):3337–3347PubMedCrossRef
92.
del Rincon I, Escalante A (2003) Atherosclerotic cardiovascular disease in rheumatoid arthritis. Curr Rheumatol Rep 5(4):278–286PubMedCrossRef
93.
Bartoloni E, Shoenfeld Y, Gerli R (2011) Inflammatory and autoimmune mechanisms in the induction of atherosclerotic damage in systemic rheumatic diseases: two faces of the same coin. Arthritis Care Res 63(2):178–183CrossRef
94.
Gonzalez-Juanatey C, Llorca J, Testa A, Revuelta J, Garcia-Porrua C, Gonzalez-Gay MA (2003) Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthritis patients without clinically evident atherosclerotic disease. Medicine 82(6):407–413PubMedCrossRef
95.
Lopez-Mejias R, Corrales A, Genre F, Hernandez JL, Ochoa R, Blanco R et al (2013) Angiopoietin-2 serum levels correlate with severity, early onset and cardiovascular disease in patients with rheumatoid arthritis. Clin Exp Rheumatol 31(5):761–766PubMed
96.
Lopez-Mejias R, Ubilla B, Genre F, Corrales A, Hernandez JL, Ferraz-Amaro I et al (2015) Osteoprotegerin concentrations relate independently to established cardiovascular disease in rheumatoid arthritis. J Rheumatol 42(1):39–45PubMedCrossRef
97.
Dessein PH, Lopez-Mejias R, Gonzalez-Juanatey C, Genre F, Miranda-Filloy JA, Llorca J et al (2014) Independent relationship of osteoprotegerin concentrations with endothelial activation and carotid atherosclerosis in patients with severe rheumatoid arthritis. J Rheumatol 41(3):429–436PubMedCrossRef
98.
Peters MJ, Symmons DP, McCarey D, Dijkmans BA, Nicola P, Kvien TK et al (2010) EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 69(2):325–331PubMedCrossRef
99.
Szekanecz Z, Kerekes G, Der H, Sandor Z, Szabo Z, Vegvari A et al (2007) Accelerated atherosclerosis in rheumatoid arthritis. Ann NY Acad Sci 1108:349–358PubMedCrossRef
100.
Gerli R, Sherer Y, Bocci EB, Vaudo G, Moscatelli S, Shoenfeld Y (2007) Precocious atherosclerosis in rheumatoid arthritis: role of traditional and disease-related cardiovascular risk factors. Ann NY Acad Sci 1108:372–381PubMedCrossRef
101.
Hjeltnes G, Hollan I, Forre O, Wiik A, Mikkelsen K, Agewall S (2011) Anti-CCP and RF IgM: predictors of impaired endothelial function in rheumatoid arthritis patients. Scand J Rheumatol 40(6):422–427PubMedCrossRef
102.
Sokolove J, Brennan MJ, Sharpe O, Lahey LJ, Kao AH, Krishnan E et al (2013) Brief report: citrullination within the atherosclerotic plaque: a potential target for the anti-citrullinated protein antibody response in rheumatoid arthritis. Arthritis Rheum 65(7):1719–1724PubMedPubMedCentralCrossRef
103.
Gonzalez-Juanatey C, Llorca J, Martin J, Gonzalez-Gay MA (2009) Carotid intima-media thickness predicts the development of cardiovascular events in patients with rheumatoid arthritis. Semin Arthritis Rheum 38(5):366–371PubMedCrossRef
104.
Gerli R, Bartoloni Bocci E, Sherer Y, Vaudo G, Moscatelli S, Shoenfeld Y (2008) Association of anti-cyclic citrullinated peptide antibodies with subclinical atherosclerosis in patients with rheumatoid arthritis. Ann Rheum Dis 67(5):724–725PubMedCrossRef
105.
Gkaliagkousi E, Gavriilaki E, Doumas M, Petidis K, Aslanidis S, Stella D (2012) Cardiovascular risk in rheumatoid arthritis: pathogenesis, diagnosis, and management. J Clin Rheumatol 18(8):422–430PubMedCrossRef
106.
Papadopoulos NG, Tsiaousis GZ, Pavlitou-Tsiontsi A, Giannakou A, Galanopoulou VK (2008) Does the presence of anti-CCP autoantibodies and their serum levels influence the severity and activity in rheumatoid arthritis patients? Clin Rev Allergy Immunol 34(1):11–15PubMedCrossRef
107.
Vazquez-Del Mercado M, Nunez-Atahualpa L, Figueroa-Sanchez M, Gomez-Banuelos E, Rocha-Munoz AD, Martin-Marquez BT et al (2015) Serum levels of anticyclic citrullinated peptide antibodies, interleukin-6, tumor necrosis factor-alpha, and C-reactive protein are associated with increased carotid intima-media thickness: a cross-sectional analysis of a cohort of rheumatoid arthritis patients without cardiovascular risk factors. Biomed Res Int 2015:342649PubMedPubMedCentral
108.
Barbarroja N, Perez-Sanchez C, Ruiz-Limon P, Castro-Villegas C, Aguirre MA, Carretero R et al (2014) Anticyclic citrullinated protein antibodies are implicated in the development of cardiovascular disease in rheumatoid arthritis. Arterioscler Thromb Vasc Biol 34(12):2706–2716PubMedCrossRef
109.
Sokolove J, Johnson DS, Lahey LJ, Wagner CA, Cheng D, Thiele GM et al (2014) Rheumatoid factor as a potentiator of anti-citrullinated protein antibody-mediated inflammation in rheumatoid arthritis. Arthritis Rheumatol 66(4):813–821PubMedPubMedCentralCrossRef
110.
Gottenberg JE, Ravaud P, Cantagrel A, Combe B, Flipo RM, Schaeverbeke T et al (2012) Positivity for anti-cyclic citrullinated peptide is associated with a better response to abatacept: data from the ‘Orencia and Rheumatoid Arthritis’ registry. Ann Rheum Dis 71(11):1815–1819PubMedCrossRef
111.
Bobbio-Pallavicini F, Caporali R, Alpini C, Moratti R, Montecucco C (2007) Predictive value of antibodies to citrullinated peptides and rheumatoid factors in anti-TNF-alpha treated patients. Ann NY Acad Sci 1109:287–295PubMedCrossRef
112.
Braun-Moscovici Y, Markovits D, Zinder O, Schapira D, Rozin A, Ehrenburg M et al (2006) Anti-cyclic citrullinated protein antibodies as a predictor of response to anti-tumor necrosis factor-alpha therapy in patients with rheumatoid arthritis. J Rheumatol 33(3):497–500PubMed
113.
Bizzaro N, Bartoloni E, Morozzi G, Manganelli S, Riccieri V, Sabatini P et al (2013) Anti-cyclic citrullinated peptide antibody titer predicts time to rheumatoid arthritis onset in patients with undifferentiated arthritis: results from a 2-year prospective study. Arthritis Res Ther 15(1):R16PubMedPubMedCentralCrossRef
114.
Elrefaei M, Boose K, McGee M, Tarrant TK, Lin FC, Fine JP et al (2012) Second generation automated anti-CCP test better predicts the clinical diagnosis of rheumatoid arthritis. J Clin Immunol 32(1):131–137PubMedCrossRef
115.
Kokkonen H, Mullazehi M, Berglin E, Hallmans G, Wadell G, Ronnelid J et al (2011) Antibodies of IgG, IgA and IgM isotypes against cyclic citrullinated peptide precede the development of rheumatoid arthritis. Arthritis Res Ther 13(1):R13PubMedPubMedCentralCrossRef
116.
Mjaavatten MD, van der Heijde D, Uhlig T, Haugen AJ, Nygaard H, Sidenvall G et al (2010) The likelihood of persistent arthritis increases with the level of anti-citrullinated peptide antibody and immunoglobulin M rheumatoid factor: a longitudinal study of 376 patients with very early undifferentiated arthritis. Arthritis Res Ther 12(3):R76PubMedPubMedCentralCrossRef
117.
Emad Y, Shehata M, Ragab Y, Saad A, Hamza H, Abou-Zeid A (2010) Prevalence and predictive value of anti-cyclic citrullinated protein antibodies for future development of rheumatoid arthritis in early undifferentiated arthritis. Mod Rheumatol 20(4):358–365PubMedCrossRef
118.
van der Linden MP, van der Woude D, Ioan-Facsinay A, Levarht EW, Stoeken-Rijsbergen G, Huizinga TW et al (2009) Value of anti-modified citrullinated vimentin and third-generation anti-cyclic citrullinated peptide compared with second-generation anti-cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis. Arthritis Rheum 60(8):2232–2241PubMedCrossRef
119.
Hafstrom I, Engvall IL, Ronnelid J, Boonen A, van der Heijde D, Svensson B (2014) Rheumatoid factor and anti-CCP do not predict progressive joint damage in patients with early rheumatoid arthritis treated with prednisolone: a randomised study. BMJ Open 4(7):e005246PubMedPubMedCentralCrossRef
120.
Esalatmanesh K, Jamali R, Jamali A, Jamali B, Nikbakht M (2012) Serum anti-cyclic citrullinated peptide antibodies may predict disease activity in rheumatoid arthritis. Rheumatol Int 32(12):3799–3805PubMedCrossRef
121.
da Mota LM, Dos Santos Neto LL, de Carvalho JF, Pereira IA, Burlingame R, Menard HA et al (2012) The presence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor on patients with rheumatoid arthritis (RA) does not interfere with the chance of clinical remission in a follow-up of 3 years. Rheumatol Int 32(12):3807–3812PubMedCrossRef
122.
Marasovic-Krstulovic D, Martinovic-Kaliterna D, Fabijanic D, Morovic-Vergles J (2011) Are the anti-cyclic citrullinated peptide antibodies independent predictors of myocardial involvement in patients with active rheumatoid arthritis? Rheumatology 50(8):1505–1512PubMedCrossRef
123.
Shidara K, Inoue E, Hoshi D, Sato E, Nakajima A, Momohara S et al (2012) Anti-cyclic citrullinated peptide antibody predicts functional disability in patients with rheumatoid arthritis in a large prospective observational cohort in Japan. Rheumatol Int 32(2):361–366PubMedCrossRef
124.
Cader MZ, Filer AD, Buckley CD, Raza K (2010) The relationship between the presence of anti-cyclic citrullinated peptide antibodies and clinical phenotype in very early rheumatoid arthritis. BMC Musculoskelet Disord 11:187PubMedPubMedCentralCrossRef
125.
Farragher TM, Lunt M, Plant D, Bunn DK, Barton A, Symmons DP (2010) Benefit of early treatment in inflammatory polyarthritis patients with anti-cyclic citrullinated peptide antibodies versus those without antibodies. Arthritis Care Res 62(5):664–675CrossRef
126.
Cuchacovich M, Catalan D, Wainstein E, Gatica H, Soto L, Aravena O et al (2008) Basal anti-cyclic citrullinated peptide (anti-CCP) antibody levels and a decrease in anti-CCP titres are associated with clinical response to adalimumab in rheumatoid arthritis. Clin Exp Rheumatol 26(6):1067–1073PubMed
127.
Mathsson L, Mullazehi M, Wick MC, Sjoberg O, van Vollenhoven R, Klareskog L et al (2008) Antibodies against citrullinated vimentin in rheumatoid arthritis: higher sensitivity and extended prognostic value concerning future radiographic progression as compared with antibodies against cyclic citrullinated peptides. Arthritis Rheum 58(1):36–45PubMedCrossRef
128.
Bukhari M, Thomson W, Naseem H, Bunn D, Silman A, Symmons D et al (2007) The performance of anti-cyclic citrullinated peptide antibodies in predicting the severity of radiologic damage in inflammatory polyarthritis: results from the Norfolk Arthritis Register. Arthritis Rheum 56(9):2929–2935PubMedPubMedCentralCrossRef
129.
Vencovsky J, Machacek S, Sedova L, Kafkova J, Gatterova J, Pesakova V et al (2003) Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis. Ann Rheum Dis 62(5):427–430PubMedPubMedCentralCrossRef
130.
Salgado E, Maneiro JR, Gomez-Reino JJ (2015) Predictors of response to TNF antagonists. Curr Pharm Des 21(2):221–232PubMedCrossRef
131.
van der Heijde DM, van Riel PL, van Leeuwen MA, van’t Hof MA, van Rijswijk MH, van de Putte LB (1992) Prognostic factors for radiographic damage and physical disability in early rheumatoid arthritis. A prospective follow-up study of 147 patients. Br J Rheumatol 31(8):519–525PubMedCrossRef
132.
Maneiro RJ, Salgado E, Carmona L, Gomez-Reino JJ (2013) Rheumatoid factor as predictor of response to abatacept, rituximab and tocilizumab in rheumatoid arthritis: systematic review and meta-analysis. Semin Arthritis Rheum 43(1):9–17PubMedCrossRef
133.
Salgado E, Maneiro JR, Carmona L, Gomez-Reino J (2014) Rheumatoid factor and response to TNF antagonists in rheumatoid arthritis: systematic review and meta-analysis of observational studies. Joint Bone Spine 81(1):41–50PubMedCrossRef
134.
Lv Q, Yin Y, Li X, Shan G, Wu X, Liang D et al (2014) The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody are not associated with the effect of anti-TNFalpha agent treatment in patients with rheumatoid arthritis: a meta-analysis. PLoS One 9(2):e89442PubMedPubMedCentralCrossRef
135.
Chen HA, Lin KC, Chen CH, Liao HT, Wang HP, Chang HN et al (2006) The effect of etanercept on anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatoid arthritis. Ann Rheum Dis 65(1):35–39PubMedCrossRef
136.
Bos WH, Bartelds GM, Wolbink GJ, de Koning MH, van de Stadt RJ, van Schaardenburg D et al (2008) Differential response of the rheumatoid factor and anticitrullinated protein antibodies during adalimumab treatment in patients with rheumatoid arthritis. J Rheumatol 35(10):1972–1977PubMed
137.
Atzeni F, Sarzi-Puttini P, Dell’ Acqua D, de Portu S, Cecchini G, Cruini C et al (2006) Adalimumab clinical efficacy is associated with rheumatoid factor and anti-cyclic citrullinated peptide antibody titer reduction: a one-year prospective study. Arthritis Res Ther 8(1):R3PubMedCrossRef
138.
Alessandri C, Bombardieri M, Papa N, Cinquini M, Magrini L, Tincani A et al (2004) Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following anti-TNFalpha therapy (infliximab) in rheumatoid arthritis is associated with clinical improvement. Ann Rheum Dis 63(10):1218–1221PubMedPubMedCentralCrossRef
139.
De Rycke L, Verhelst X, Kruithof E, Van den Bosch F, Hoffman IE, Veys EM et al (2005) Rheumatoid factor, but not anti-cyclic citrullinated peptide antibodies, is modulated by infliximab treatment in rheumatoid arthritis. Ann Rheum Dis 64(2):299–302PubMedCrossRef
140.
Kelly CA, Saravanan V, Nisar M, Arthanari S, Woodhead FA, Price-Forbes AN et al (2014) Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics—a large multicentre UK study. Rheumatology 53(9):1676–1682PubMedCrossRef
141.
Amara K, Steen J, Murray F, Morbach H, Fernandez-Rodriguez BM, Joshua V et al (2013) Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward citrullinated autoantigen recognition. J Exp Med 210(3):445–455PubMedPubMedCentralCrossRef
142.
Leandro MJ, Cambridge G, Ehrenstein MR, Edwards JC (2006) Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum 54(2):613–620PubMedCrossRef
143.
Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR et al (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350(25):2572–2581PubMedCrossRef
144.
Emery P, Fleischmann R, Filipowicz-Sosnowska A, Schechtman J, Szczepanski L, Kavanaugh A et al (2006) The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 54(5):1390–1400PubMedCrossRef
145.
Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC et al (2006) Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 54(9):2793–2806PubMedCrossRef
146.
Tak PP, Rigby WF, Rubbert-Roth A, Peterfy CG, van Vollenhoven RF, Stohl W et al (2011) Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis 70(1):39–46PubMedCrossRef
147.
Lal P, Su Z, Holweg CT, Silverman GJ, Schwartzman S, Kelman A et al (2011) Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment. Arthritis Rheum 63(12):3681–3691PubMedCrossRef
148.
Emery P, Deodhar A, Rigby WF, Isaacs JD, Combe B, Racewicz AJ et al (2010) Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis 69(9):1629–1635PubMedPubMedCentralCrossRef
149.
Tak PP, Rigby W, Rubbert-Roth A, Peterfy C, van Vollenhoven RF, Stohl W et al (2012) Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE. Ann Rheum Dis 71(3):351–357PubMedCrossRef
150.
Mease PJ, Cohen S, Gaylis NB, Chubick A, Kaell AT, Greenwald M et al (2010) Efficacy and safety of retreatment in patients with rheumatoid arthritis with previous inadequate response to tumor necrosis factor inhibitors: results from the SUNRISE trial. J Rheumatol 37(5):917–927PubMedCrossRef
151.
Shetty S, Fisher MC, Ahmed AR (2013) Review on the influence of protocol design on clinical outcomes in rheumatoid arthritis treated with rituximab. Ann Pharmacother 47(3):311–323PubMedCrossRef
152.
Sellam J, Hendel-Chavez H, Rouanet S, Abbed K, Combe B, Le Loet X et al (2011) 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(4):933–938PubMedCrossRef
153.
Chatzidionysiou K, Lie E, Nasonov E, Lukina G, Hetland ML, Tarp U et al (2011) Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed: pooled data from 10 European registries. Ann Rheum Dis 70(9):1575–1580PubMedCrossRef
154.
Narvaez J, Diaz-Torne C, Ruiz JM, Hernandez MV, Torrente-Segarra V, Ros S et al (2011) Predictors of response to rituximab in patients with active rheumatoid arthritis and inadequate response to anti-TNF agents or traditional DMARDs. Clin Exp Rheumatol 29(6):991–997PubMed
155.
Couderc M, Mathieu S, Pereira B, Glace B, Soubrier M (2013) Predictive factors of rituximab response in rheumatoid arthritis: results from a French university hospital. Arthritis Care Res 65(4):648–652CrossRef
156.
Gardette A, Ottaviani S, Tubach F, Roy C, Nicaise-Roland P, Palazzo E et al (2014) High anti-CCP antibody titres predict good response to rituximab in patients with active rheumatoid arthritis. Joint Bone Spine 81(5):416–420PubMedCrossRef
157.
Quartuccio L, Salvin S, Saracco M, Lombardi S, Fabris M, Mansutti E et al (2009) Rheumatoid factor positivity rather than anti-CCP positivity, a lower disability and a lower number of anti-TNFalpha agents failed are associated with response to rituximab in rheumatoid arthritis. Reumatismo 61(3):182–186PubMed
158.
Buch MH, Smolen JS, Betteridge N, Breedveld FC, Burmester G, Dorner T et al (2011) Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis 70(6):909–920PubMedPubMedCentralCrossRef
159.
Vital EM, Rawstron AC, Dass S, Henshaw K, Madden J, Emery P et al (2011) Reduced-dose rituximab in rheumatoid arthritis: efficacy depends on degree of B cell depletion. Arthritis Rheum 63(3):603–608PubMedCrossRef
160.
Nakou M, Katsikas G, Sidiropoulos P, Bertsias G, Papadimitraki E, Raptopoulou A et al (2009) Rituximab therapy reduces activated B cells in both the peripheral blood and bone marrow of patients with rheumatoid arthritis: depletion of memory B cells correlates with clinical response. Arthritis Res Ther 11(4):R131PubMedPubMedCentralCrossRef
161.
Thurlings RM, Vos K, Wijbrandts CA, Zwinderman AH, Gerlag DM, Tak PP (2008) Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response. Ann Rheum Dis 67(7):917–925PubMedCrossRef
162.
Cambridge G, Leandro MJ, Edwards JC, Ehrenstein MR, Salden M, Bodman-Smith M et al (2003) Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum 48(8):2146–2154PubMedCrossRef
163.
Cambridge G, Stohl W, Leandro MJ, Migone TS, Hilbert DM, Edwards JC (2006) Circulating levels of B lymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: relationships with B cell depletion, circulating antibodies, and clinical relapse. Arthritis Rheum 54(3):723–732PubMedCrossRef
164.
Toubi E, Kessel A, Slobodin G, Boulman N, Pavlotzky E, Zisman D et al (2007) Changes in macrophage function after rituximab treatment in patients with rheumatoid arthritis. Ann Rheum Dis 66(6):818–820PubMedCrossRef
165.
Tsiakalos AP, Avgoustidis NK, Moutsopoulos HM (2008) Rituximab therapy in Greek patients with rheumatoid arthritis. Biologics 2(4):911–916PubMedPubMedCentral
166.
Rosengren S, Wei N, Kalunian KC, Zvaifler NJ, Kavanaugh A, Boyle DL (2008) Elevated autoantibody content in rheumatoid arthritis synovia with lymphoid aggregates and the effect of rituximab. Arthritis Res Ther 10(5):R105PubMedPubMedCentralCrossRef
167.
Kormelink TG, Tekstra J, Thurlings RM, Boumans MH, Vos K, Tak PP et al (2010) Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity. Ann Rheum Dis 69(12):2137–2144PubMedCrossRef
168.
Vancsa A, Szabo Z, Szamosi S, Bodnar N, Vegh E, Gergely L et al (2013) Longterm effects of rituximab on B cell counts and autoantibody production in rheumatoid arthritis: use of high-sensitivity flow cytometry for more sensitive assessment of B cell depletion. J Rheumatol 40(5):565–571PubMedCrossRef
169.
Lindenberg L, Spengler L, Bang H, Dorner T, Maslyanskiy AL, Lapin SV et al (2015) Restrictive IgG antibody response against mutated citrullinated vimentin predicts response to rituximab in patients with rheumatoid arthritis. Arthritis Res Ther 17:206PubMedPubMedCentralCrossRef
170.
Tanaka T, Kishimoto T (2012) Immunotherapeutic implication of IL-6 blockade. Immunotherapy 4(1):87–105PubMedCrossRef
171.
Kawashiri SY, Kawakami A, Iwamoto N, Fujikawa K, Aramaki T, Tamai M et al (2011) Disease activity score 28 may overestimate the remission induction of rheumatoid arthritis patients treated with tocilizumab: comparison with the remission by the clinical disease activity index. Mod Rheumatol 21(4):365–369PubMedCrossRef
172.
Pers YM, Fortunet C, Constant E, Lambert J, Godfrin-Valnet M, De Jong A et al (2014) Predictors of response and remission in a large cohort of rheumatoid arthritis patients treated with tocilizumab in clinical practice. Rheumatology 53(1):76–84PubMedCrossRef
173.
Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C et al (2006) Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med 144(12):865–876PubMedCrossRef
174.
Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J et al (2005) Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med 353(11):1114–1123PubMedCrossRef
175.
Bathon J, Robles M, Ximenes AC, Nayiager S, Wollenhaupt J, Durez P et al (2011) Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes. Ann Rheum Dis 70(11):1949–1956PubMedCrossRef
176.
Emery P, Durez P, Dougados M, Legerton CW, Becker JC, Vratsanos G et al (2010) Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial). Ann Rheum Dis 69(3):510–516PubMedCrossRef
177.
Emery P, Burmester GR, Bykerk VP, Combe BG, Furst DE, Barre E et al (2015) Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis 74(1):19–26PubMedCrossRef
178.
Nusslein HG, Alten R, Galeazzi M, Lorenz HM, Boumpas D, Nurmohamed MT et al (2014) Real-world effectiveness of abatacept for rheumatoid arthritis treatment in European and Canadian populations: a 6-month interim analysis of the 2-year, observational, prospective ACTION study. BMC Musculoskelet Disord 15:14PubMedPubMedCentralCrossRef
179.
Weinblatt ME, Schiff M, Valente R, van der Heijde D, Citera G, Zhao C et al (2013) Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum 65(1):28–38PubMedPubMedCentralCrossRef
180.
Kubo S, Nakayamada S, Nakano K, Hirata S, Fukuyo S, Miyagawa I et al (2015) Comparison of the efficacies of abatacept and tocilizumab in patients with rheumatoid arthritis by propensity score matching. Ann Rheum Dis [Epub ahead of print]
181.
Anno S, Inui K, Mamoto K, Okano T, Sugioka Y, Tada M et al (2015) Abatacept might not alter anti-cyclic citrullinated peptide levels in established rheumatoid arthritis patients. Ann Rheum Dis 74(Suppl2):1058
182.
Fujii T, Sekiguchi M, Matsui K, Kitano M, Hashimoto M, Ohmura K et al (2013) Very high titer of anti-citrullinated protein antibodies is associated with the achievement of clinical remission by abatacept in biologic-naïve patients with rheumatoid arthritis (the Abroad study). Ann Rheum Dis 72(Suppl3):889
183.
Scarsi M, Paolini L, Ricotta D, Pedrini A, Piantoni S, Caimi L et al (2014) Abatacept reduces levels of switched memory B cells, autoantibodies, and immunoglobulins in patients with rheumatoid arthritis. J Rheumatol 41(4):666–672PubMedCrossRef
184.
Huizinga TWJ, Connolly SE, Furst DE, Bykerk VP, Burmester G, Combe B et al (2014) The impact on anti-citrullinated protein antibody isotypes and epitope fine specificity in patients with early RA treated with abatacept and methotrexate. Arthritis Rheum 66(Supl 10):S666
185.
Klein U, Rajewsky K, Kuppers R (1998) Human immunoglobulin (Ig)M+ IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J Exp Med 188(9):1679–1689PubMedPubMedCentralCrossRef
186.
Martin Mola E, Balsa A, Martinez Taboada V, Sanmarti R, Marenco JL, Navarro Sarabia F et al (2013) Abatacept use in rheumatoid arthritis: evidence review and recommendations. Reumatol Clin 9(1):5–17PubMedCrossRef
187.
Matsutani T, Murakami M, Sekiguchi M, Matsui K, Kitano M, Namiki M et al (2013) Abatacept treatment suppresses T cell activation in anti-cyclic citrullinated peptide antibody (ACPA) positive RA patients but not in ACPA negative RA patients. Ann Rheum Dis 72(Suppl3):614
188.
Ramos-Remus C, Castillo-Ortiz JD, Aguilar-Lozano L, Padilla-Ibarra J, Sandoval-Castro C, Vargas-Serafin CO et al (2015) Autoantibodies in predicting rheumatoid arthritis in healthy relatives of rheumatoid arthritis patients. Arthritis Rheum 67(11):2837–2844CrossRef
189.
Onishi S, Yoshio T, Nagashima T, Minota S (2010) Decrease in the levels of anti-cyclic citrullinated peptide antibody in Japanese patients with rheumatoid arthritis who responded to anti-tumor necrosis factor-α. Mod Rheumatol 20(5):528–530PubMedCrossRef
Metadata
Title
Anti-citrullinated peptide antibodies and their value for predicting responses to biologic agents: a review
Authors
Emilio Martin-Mola
Alejandro Balsa
Rosario García-Vicuna
Juan Gómez-Reino
Miguel Angel González-Gay
Raimon Sanmartí
Estíbaliz Loza
Publication date
01-08-2016
Publisher
Springer Berlin Heidelberg
Published in
Rheumatology International / Issue 8/2016
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-016-3506-3

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11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

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