Pathogenic role of antibodies to citrullinated proteins in rheumatoid arthritis

Expert Review of Clinical Immunology

Volumn 2, Issue 3, 2006, Pages 365-375

  Kinloch, Andrew J ^a   Lundberg, Karin E ^a   Moyes, David ^a   Venables, Patrick J ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA ENOLASE; COLLAGEN TYPE 2; DISEASE MODIFYING ANTIRHEUMATIC DRUG; FIBRIN; METHOTREXATE; PACLITAXEL; PROTEIN ANTIBODY; TUMOR NECROSIS FACTOR ANTIBODY; VIMENTIN;

ALLELE; AUTOIMMUNITY; CHRONIC INFLAMMATION; DISEASE PREDISPOSITION; DISEASE SEVERITY; ENVIRONMENTAL FACTOR; HEREDITY; HUMAN; IMMUNE RESPONSE; INFECTION; JOINT; NONHUMAN; PATHOGENESIS; PROTEIN SYNTHESIS; RESPIRATORY SYSTEM; REVIEW; RHEUMATOID ARTHRITIS; SMOKING;

EID: 33748515701     PISSN: 1744666X     EISSN: None     Source Type: Journal    
DOI: 10.1586/1744666X.2.3.365     Document Type: Review

References (99)

1. Renaudineau Y, Jamin C, Saraux A, Youinou, P. Rheumatoid factor on a daily basis. Autoimmunity 38(1), 11-16 (2005).
2. van Venrooij W, Hazes J, Visser H. Anticitrullinated protein/peptide antibody and its role in the diagnosis and prognosis of early rheumatoid arthritis. Neth. J. Med. 60(10), 383-388 (2002).
3. Forslind K, Ahlmen M, Eberhardt K, Hafstrom I, Svensson B; BARFOT Study Group. Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Ann. Rheum. Dis. 63(9), 1090-1095 (2004).
4. Kroot E, de Jong BA, van Leeuwen MA et al. The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 43(8), 1831-1835 (2004).
5. Nielen M, van Schaardenburg D, Reesink HW et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 50(2), 380-386 (2004).
6. Quinn M, Gough AK, Green MJ et al. Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome. Rheumatology 45, 478-480 (2006).
7. Rantapaa-Dahlqvist S, de Jong BA, Berglin E et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 48(10), 2741-2749 (2003).
8. van Gaalen FA, Linn-Rasker SP, van Venrooij WJ et al. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum. 50(3), 709-715 (2004).
9. Vencovsky J, Machacek S, Sedova L et al. Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis. Ann. Rheum. Dis. 62(5), 427-430 (2003).
10. Vossenaar ER, Zendman AJ, van Venrooij WJ, Pruijn GJ. PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. Bioessays 25(11), 1106-1118 (2003).
11. Nachat R, Mechin MC, Takahara H et al. Peptidylarginine deiminase isoforms 1-3 are expressed in the epidermis and involved in the deimination of K1 and filaggrin. J. Invest. Dermatol. 124(2), 384-393 (2005).
12. Senshu T, Kan S, Ogawa H, Manabe M, Asaga H. Preferential deimination of keratin K1 and filaggrin during the terminal differentiation of human epidermis. Biochem. Biophys. Res. Commun. 225(3), 712-719 (1996).
13. Cuthbert G, Daujat S, Snowden AW et al. Histone deimination antagonizes arginine methylation. Cell 118(5), 545-553 (2004).
14. Wang Y, Wysocka J, Sayegh J et al. Human PAD4 regulates histone arginine methylation levels via demethylimination. Science 306, 279-283 (2004).
15. Senshu T, Akiyama K, Ishigami AKN. Studies on specificity of peptidylarginine deiminase reactions using an immunochemical probe that recognizes an enzymatically deiminated partial sequence of mouse keratin K1. J. Dermatol. Sci. 21(2), 113-126 (1999).
16. Nakayama-Hamada M, Suzuki A, Kubota K et al. Comparison of enzymatic properties between hPADI2 and hPADI4. Biochem Biophys. Res. Commun. 327(1), 192-200 (2005).
17. Chang X, Yamada R, Suzuki A et al. Localization of peptidylarginine deiminase 4 (PADI4) and citrullinated protein in synovial tissue of rheumatoid arthritis. Rheumatology (Oxf.) 44, 40-50 (2005).
18. De Rycke L, Nicholas AP, Cantaert T et al. Synovial intracellular citrullinated proteins colocalizing with peptidyl arginine deiminase as pathophysiologically relevant antigenic determinants of rheumatoid arthritis-specific humoral autoimmunity. Arthritis Rheum. 52(8), 2323-2330 (2005).
19. Suzuki A, Yamada R, Chang X et al. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat. Genet. 34(4), 395-402 (2003).
20. Vossenaar ER, Radstake TR, van der Heijden A et al. Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages. Ann. Rheum. Dis. 63(4), 373-3781 (2004).
21. Moscarello M, Pritzker L, Mastronardi F, Wood D. Peptidylarginine deiminase: a candidate factor in demyelinating disease. J. Neurochem. 81(2), 335-343 (2002).
22. Mastronardi F, Moscarello M. Molecules affecting myelin stability: a novel hypothesis regarding the pathogenesis of multiple sclerosis. J Neurosci Res. 80(3), 301-308 (2005).
23. Nakashima K, Hagiwara T, Yamada M. Nuclear localization of peptidylarginine deiminase V and histone deimination in granulocytes. J. Biol. Chem. 277(51), 49562-49568 (2002).
24. Zendman A, van Venrooij W, Pruijn G. Use and significance of anti-CCP autoantibodies in rheumatoid arthritis. Rheumatology (Oxford) 45(1), 20-25 (2006).
25. Girbal-Neuhauser E, Durieux JJ, Arnaud M 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).
26. Sebbag M, Simon M, Vincent C et al. The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies. J. Clin. Invest. 95(6), 2672-2679 (1995).
27. Masson-Bessiere C, Sebbag M, Girbal-Neuhauser E 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(6), 4177-4184 (2001).
28. Menard HA, Lapointe E, Rochdi MD, Zhou ZJ. Insights into rheumatoid arthritis derived from the Sa immune system. Arthritis Res. 2(6), 429-432 (2000).
29. Vossenaar ER, Despres N, Lapointe E et al. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthritis Res. Ther. 6(2), R142-R150 (2004).
30. Burkhardt H, Sehnert B, Bockermann R, Engstrom A, Kalden JR, Holmdahl R. Humoral immune response to citrullinated collagen type II determinants in early rheumatoid arthritis. Eur. J. Immunol. 35, 1643-1652 (2005).
31. Kinloch A, Tatzer V, Wait R et al. Identification of citrullinated α-enolase as a candidate autoantigen in rheumatoid arthritis. Arthritis Res. Ther. 7(6), R1421-R1429 (2005).
32. Pratesi F, Tommasi C, Anzilotti C, Chimenti D, Migliorini P. Deiminated Epstein-Barr virus nuclear antigen 1 is a target of anti-citrullinated protein antibodies in rheumatoid arthritis. Arthritis Rheum. 54(3), 733-741 (2006).
33. Nienhuis RL, Mandema E. A new serum factor in patients with rheumatoid arthritis; the antiperinuclear factor. Ann. Rheum. Dis. 23, 302-305 (1964).
34. Nijenhuis S, Zendman A, Vossenaar E, Pruijn G, vanVenrooij W. Autoantibodies to citrullinated proteins in rheumatoid arthritis: clinical performance and biochemical aspects of an RA-specific marker. Clin. Chim. Acta 350(1-2), 17-34 (2004).
35. Young BJ, Mallya RK, Leslie RD, Clark CJ, Hamblin TJ. Anti-keratin antibodies in rheumatoid arthritis. Br. Med. J. 2, 97-99 (1979).
36. Simon M, Girbal E, Sebbag M et al. The cytokeratin filament-aggregating protein filaggrin is the target of the so-called "antikeratin antibodies," antibodies specific for rheumatoid arthritis. J. Clin. Invest. 92, 1387 (1993).
37. Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J. Clin. Invest. 101(1), 273-281 (1998).
38. Schellekens G, Visser H, de Jong BA et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 43(1), 155-163 (2000).
39. Masson-Bessiere C, Sebbag M, Durieux JJ et al. In the rheumatoid pannus, antifilaggrin autoantibodies are produced by local plasma cells and constitute a higher proportion of IgG than in synovial fluid and serum. Clin. Exp. Immunol. 119(3), 544-552 (2000).
40. Nielen M, van der Horst AR, van Schaardenburg D et al. Antibodies to citrullinated human fibrinogen (ACF) have diagnostic and prognostic value in early arthritis. Ann. Rheum. Dis. 64(8), 1199-1204 (2005).
41. Chapuy-Regaud S, Sebbag M, Baeten D et al. Fibrin deimination in synovial tissue is not specific for rheumatoid arthritis but commonly occurs during synovitides. J. Immunol. 174(8), 5057-5064 (2005).
42. Despres N. The Sa system: a novel antigen-antibody system specific for rheumatoid arthritis. J. Rheum. 21(6), 1027-1033 (1994).
43. Boire G, Cossette P, de Brum-Fernandes AJ et al. Anti-Sa antibodies and antibodies against cyclic citrullinated peptide are not equivalent as predictors of severe outcomes in patients with recent-onset polyarthritis. Arthritis Res. Ther. 7(3), R592-R603 (2005).
44. Lundberg K, Nijenhuis S, Vossenaar ER et al. Citrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity. Arthritis Res. Ther. 7(3), R458-R467 (2005).
45. 3. J. Biol. Chem. 274(39), 27786-27792 (1999).
46. Kemp E, Herd LM, Waterman EA, Wilson AG, Weetman AP, Watson PP. Immunoscreening of phage-displayed cDNA-encoded polypeptides identifies B cell targets in autoimmune disease. Biochem Biophys. Res. Commun. 298(1), 169-177 (2002).
47. Lee K, Chung HS, Kim HS et al. Human α-enolase from endothelial cells as a target antigen of anti-endothelial cell antibody in Behcet's disease. Arthritis Rheum. 48(7), 2025-2035 (2003).
48. Moodie F, Leaker B, Cambridge G, Totty N, Segal A. α-enolase: a novel cytosolic autoantigen in ANCA positive vasculitis. Kidney Int. 43(3), 675-681 (1993).
49. MacGregor A, Snieder H, Rigby AS et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum. 43(1), 30-37 (2000).
50. de Vries R, Huizinga T, Toes R. Redefining the HLA and RA association: to be or not to be anti-CCP positive. J. Autoimmun. 25 (Suppl.), 21-25 (2005).
51. Huizinga T, Amos CI, van der Helm-van Mil AH 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(11), 3433-3438 (2005).
52. Klareskog L, Stolt P, Lundberg K 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(1), 38-46 (2006).
53. Hil J, Southwood S, Sette A, Jevnikar AM, Bell DA, Cairns E. Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. J. Immunol. 171(2), 538-541 (2003).
54. Vossenaar E, Robinson W. Citrullination and autoimmune disease: 8th Bertine Koperberg meeting. Ann. Rheum. Dis. 64(10), 1513-1515 (2005).
55. Hida S, Miura NN, Adachi Y, Ohno N. Influence of arginine deimination on antigenicity of fibrinogen. J. Autoimmun. 23(2), 141-150 (2004).
56. Rubin B, Sonderstrup G. Citrullination of self-proteins and autoimmunity. Scand. J. Immunol. 60, 112-120 (2004).
57. Shiozawa S, Hayashi S, Tsukamoto Y et al. Identification of the gene loci that predispose to rheumatoid arthritis. Int. Immunol. 10(12), 1891-1895 (1998).
58. Cornelis F, Faure S, Martinez M et al. New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study. Proc. Natl Acad. Sci. USA 95(18), 10746-10750 (1998).
59. Ikari K, Kuwahara M, Nakamura T et al. Association between PADI4 and rheumatoid arthritis: a replication study. Arthritis Rheum. 52(10), 3054-3057 (2005).
60. Kang C, Lee HS, Ju H, Cho H, Kang C, Bae SC. A functional haplotype of the PADI4 gene associated with increased rheumatoid arthritis susceptibility in Koreans. Arthritis Rheum. 54(1), 90-96 (2006).
61. Barton A, Bowes J, Eyre S et al. A functional haplotype of the PADI4 gene associated with rheumatoid arthritis in a Japanese population is not associated in a United Kingdom population. Arthritis Rheum. 50(4), 1117-1121 (2004).
62. Barton A, Barton A, Bowes J et al. Investigation of polymorphisms in the PADI4 gene in determining severity of inflammatory polyarthritis. Ann. Rheum. Dis. 64(9), 1311-1315 (2005).
63. Caponi L, Petit-Teixeira E, Sebbag M et al. A family based study shows no association between rheumatoid arthritis and the PADI4 gene in a white French population. Ann. Rheum. Dis. 64(4), 587-593 (2005).
64. Martinez A, Valdivia A, Pascual-Salcedo D et al. PADI4 polymorphisms are not associated with rheumatoid arthritis in the Spanish population. Rheumatology (Oxford) 44(10), 1263-1266 (2005).
65. Plenge R, Padyukov L, Remmers EF et al. Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4. Am. J. Hum. Genet. 77(6), 1044-1060 (2005).
66. Cantaert T, Coucke P, De Rycke L, Veys EM, De Keyser F, Baeten D. Functional haplotypes of PADI4: relevance for rheumatoid arthritis specific synovial intracellular citrullinated proteins and anticitrullinated protein antibodies. Ann. Rheum. Dis. 64(9), 1316-1320 (2005).
67. Hoppe B, Haupl T, Gruber R et al. Detailed analysis of the variability of peptidylarginine deiminase type 4 in German patients with rheumatoid arthritis: a case-control study. Arthritis Res. Ther. 8(2), R34 (2006).
68. Iwamoto T, Ikari K, Nakamura T et al. Association between PADI4 and rheumatoid arthritis: a meta-analysis. Rheumatology (Oxford) (2006) (Epub ahead of print).
69. Harney S, Meisel C, Sims AM, Woon PY, Wordsworth BP, Brown MA. Genetic and genomic studies of PADI4 in rheumatoid arthritis. Rheumatology (Oxford) 44(7), 869-872 (2005).
70. Linn-Rasker S, van der Helm-van Mil AH, van Gaalen FA et al. Smoking is risk factor for anti-CCP antibodies only in RA patients, that carry HLA-DRB1 shared epitope alleles. Ann. Rheum. Dis. 65(3), 366-371 (2006).
71. Carty S, Snowden N, Silman A. Should infection still be considered as the most likely triggering factor for rheumatoid arthritis? J. Rheumatol. 30(3), 425-429 (2003).
72. McGraw WT, Potempa J, Farley D, Travis J. Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase. Infect. Immun. 67(7), 3248-3256 (1999).
73. Rosenstein E, Greenwald R, Kushner LGW. Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis. Inflammation 28, 311-318 (2004).
74. Ogrendik M, Kokino S, Ozdemir F, Bird P, Hamlet S. Serum antibodies to oral anaerobic bacteria in patients with rheumatoid arthritis. Med. Gen. Med. 7(2), 2 (2005).
75. Vossenaar E, van Venrooij W. Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis. Arthritis Res. Ther. 6(3), 107-111 (2004).
76. Vossenaar E, van Venrooij WJ. The presence of citrullinated proteins is not specific for rheumatoid synovial tissue. Arthritis Rheum. 50(11), 3485-3494 (2004).
77. Chang X, Yamada R, Suzuki A, Kochi Y, Sawada T, Yamamoto K. Citrullination of fibronectin in rheumatoid arthritis synovial tissue. Rheumatology (Oxford) 44(11), 1374-1382 (2005).
78. Sambandam T, Belousova M, Accaviti-Loper MA. Increased peptidylarginine deiminase type II in hypoxic astrocytes. Biochem Biophys. Res. Commun. 325(4), 1324-1329 (2004).
79. Madge L, Pober J. TNF signaling in vascular endothelial cells. Exp. Mol. Pathol. 70(3), 317-325 (2001).
80. Brechard S, Bueb J, Tschirhart E. Interleukin-8 primes oxidative burst in neutrophil-like HL-60 through changes in cytosolic calcium. Cell Calcium 37(6), 531-540 (2005).
81. Wiik A. Granulocyte-specific antinuclear antibodies. Possible significance for the pathogenesis, clinical features and diagnosis of rheumatoid arthritis. Allergy 35(4), 263-289 (1980).
82. Vossenaar E, van Boekel MA, van Venrooij WJ et al. Absence of citrulline-specific autoantibodies in animal models of autoimmunity. Arthritis Rheum. 50(7), 2370-2372 (2004).
83. Lopez-Hoyos M, Marquina R, Tamayo et al. Defects in the regulation of B cell apoptosis are required for the production of citrullinated peptide autoantibodies in mice. Arthritis Rheum. 48(8), 2353-2361 (2003).
84. Vossenaar ER, Nijenhuis S, Helsen MM et al. Citrullination of synovial proteins in murine models of rheumatoid arthritis. Arthritis Rheum. 48(9), 2489-2500 (2003).
85. Iwaki-Egawa S, Matsuno H, Ogawa YYW. Production of anti-CCP antibodies and matrix metalloproteinase-3 by human rheumatoid arthritis synovial tissues using SCID mice. Ann. Rheum. Dis. 64(7), 1094-1095 (2005).
86. Alessandri C, Bombardieri M, Papa N et al. Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following anti-TNFα therapy (infliximab) in rheumatoid arthritis is associated with clinical improvement. Ann. Rheum. Dis. 63(10), 1218-1221 (2004).
87. Atzeni F, Sarzi-Puttini P, Dell'Acqua D et al. 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), R3 (2005) (Epub ahead of print).
88. Bobbio-Pallavicini F, Alpini C, Caporali R, Avalle S, Bugatti S, Montecucco C. Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment. Arthritis Res. Ther. 6(3), R264-R272 (2004).
89. Chen H, Lin KC, Chen CH et al. The effect of etanercept on anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatoid arthritis. Ann. Rheum. Dis. 65(1), 35-39 (2006).
90. Caramaschi P, Biasi D, Tonolli E et al. Antibodies against cyclic citrullinated peptides in patients affected by rheumatoid arthritis before and after infliximab treatment. Rheumatol. Int. 26(1), 58-62 (2005).
91. Yazdani-Biuki B, Stadlmaier E, Mulabecirovic A et al. Blockade of tumour necrosis factor α significantly alters the serum level of IgG- and IgA-rheumatoid factor in patients with rheumatoid arthritis. Ann. Rheum. Dis. 64(8), 1224-1226 (2005).
92. De Rycke L, Peene I, Hoffman IE et al. Rheumatoid factor, but not anti-cyclic citrullinated peptide antibodies, is modulated by infliximab treatment in rheumatoid arthritis. Ann. Rheum. Dis. 64(2), 299-302 (2005).
93. Spadaro A, Riccieri V. Methotrexate effect on anti-cyclic citrullinated peptide antibody levels in rheumatoid arthritis. Ann. Rheum. Dis. 64(8), 1241-1242 (2005).
94. Menard H, Lora M, Zhou Z. Methotrexate reduces protein citrullination in vitro: a possible explanation for its singular in vivo effectivenss in rheumatoid arthritis. American College of Rheumatology Conference (2005) (Abstract 901).
95. Pritzker L, Moscarello M. A novel microtubule independent effect of paclitaxel: the inhibition of peptidylarginine deiminase from bovine brain. Biochim. Biophys. Acta. 1388(1), 154-160 (1998).
96. Yoo W, Baek H. Remission of rheumatoid arthritis with taxol in a patient with breast carcinoma. J. Rheumatol. 27(6), 1572-1573 (2000).
97. Lainer D, Brahn E. New antiangiogenic strategies for the treatment of proliferative synovitis. Expert Opin. Investig. Drugs. 14(1), 1-17 (2005).
98. Kurose AYW, Yoshida M, Sawai T. Effects of paclitaxel on cultured synovial cells from patients with rheumatoid arthritis. Cytometry 44(4), 349-354 (2001).
99. Arsenault A, Lhotak S, Hunter W, Banquerigo M, Brahn E. Taxol (paclitaxel) involution of articular cartilage destruction in collagen induced arthritis: an ultrastructural demonstration of an increased superficial chondroprotective layer. J. Rheumatol. 27(3), 582-588 (2000).