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Published in: Rheumatology International 3/2009

01-01-2009 | Original Article

Anti-cyclic citrullinated peptide antibody is associated with radiographic erosion in rheumatoid arthritis independently of shared epitope status

Authors: Churl Hyun Im, Eun Ha Kang, Hee Jung Ryu, Jung Hwa Lee, Eun Young Lee, Yun Jong Lee, Eun Bong Lee, Yeong Wook Song

Published in: Rheumatology International | Issue 3/2009

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Abstract

Shared epitope (SE) and anti-cyclic citrullinated peptide (CCP) antibody are known to be associated with rheumatoid arthritis (RA). The authors investigated their adjusted effects on RA from Korean population. Clinical features were evaluated in 226 RA patients; 164 healthy controls were enrolled. HLA-DRB1 typing for SE was done by polymerase chain reaction. Anti-CCP antibody levels were determined by enzyme linked immunosorbent assay. Logistic regression analysis method was used for adjusted effects. SE and anti-CCP antibody were associated with RA susceptibility. Anti-CCP antibody was associated with RA susceptibility independent of SE [odds ratio, OR 179.9 (95% confidence interval, CI 40.8–792.2), P < 0.001]. Anti-CCP antibody was associated with radiographic erosive changes independent of SE or rheumatoid factor [OR 3.9 (95% CI 1.1–13.3), P = 0.032]. Anti-CCP antibody was strongly associated with RA susceptibility and radiographic erosion of RA patients, independent of SE in Korean.
Literature
1.
go back to reference 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 30:1205–1213PubMedCrossRef 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 30:1205–1213PubMedCrossRef
2.
go back to reference Reveille JD (1998) The genetic contribution to the pathogenesis of rheumatoid arthritis. Curr Opin Rheumatol 10:187–200PubMedCrossRef Reveille JD (1998) The genetic contribution to the pathogenesis of rheumatoid arthritis. Curr Opin Rheumatol 10:187–200PubMedCrossRef
3.
go back to reference Del Rincon I, Battafarano DF, Arroyo RA, Murphy FT, Fischbach M, Escalante A (2003) Ethnic variation in the clinical manifestations of rheumatoid arthritis: role of HLA-DRB1 alleles. Arthritis Rheum 49:200–208PubMedCrossRef Del Rincon I, Battafarano DF, Arroyo RA, Murphy FT, Fischbach M, Escalante A (2003) Ethnic variation in the clinical manifestations of rheumatoid arthritis: role of HLA-DRB1 alleles. Arthritis Rheum 49:200–208PubMedCrossRef
4.
go back to reference Hong GH, Park MH, Takeuchi F, Oh MD, Song YW, Nabeta H, Nakano K, Ito K, Park KS (1996) Association of specific amino acid sequence of HLA-DR with rheumatoid arthritis in Koreans and its diagnostic value. J Rheumatol 23:1699–1703PubMed Hong GH, Park MH, Takeuchi F, Oh MD, Song YW, Nabeta H, Nakano K, Ito K, Park KS (1996) Association of specific amino acid sequence of HLA-DR with rheumatoid arthritis in Koreans and its diagnostic value. J Rheumatol 23:1699–1703PubMed
5.
go back to reference Lim MK, Choi SW, Lee CK, Ju YS, Cho YS, Kim SM, Shin MJ, Oh HB, Yoo B, Moon HB (2001) HLA-DR4 is not a severity marker in Korean patients with rheumatoid arthritis. J Korean Rheum Assoc 8:8–13 Lim MK, Choi SW, Lee CK, Ju YS, Cho YS, Kim SM, Shin MJ, Oh HB, Yoo B, Moon HB (2001) HLA-DR4 is not a severity marker in Korean patients with rheumatoid arthritis. J Korean Rheum Assoc 8:8–13
6.
go back to reference 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 4:87–93PubMedCrossRef 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 4:87–93PubMedCrossRef
7.
go back to reference Ward MM (2003) Clinical epidemiology: diagnostic and prognostic tests. Curr Opin Rheumatol 15:104–109PubMedCrossRef Ward MM (2003) Clinical epidemiology: diagnostic and prognostic tests. Curr Opin Rheumatol 15:104–109PubMedCrossRef
8.
go back to reference Schellekens GA, Visser H, de Jong BAW, van den Hoogen FH, Hazes JM, Breedeveld FC, van Venrooij WJ (2000) The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43:155–163PubMedCrossRef Schellekens GA, Visser H, de Jong BAW, van den Hoogen FH, Hazes JM, Breedeveld FC, van Venrooij WJ (2000) The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43:155–163PubMedCrossRef
9.
go back to reference Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, Sundin U, van Venrooij WJ (2003) Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 48:2741–2749PubMedCrossRef Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, Sundin U, van Venrooij WJ (2003) Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 48:2741–2749PubMedCrossRef
10.
go back to reference Van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, de Jong BA, Breedveld FC, Verweij CL, Toes RE, Huizinga TW (2004) Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum 50:709–715PubMedCrossRef Van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, de Jong BA, Breedveld FC, Verweij CL, Toes RE, Huizinga TW (2004) Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum 50:709–715PubMedCrossRef
11.
go back to reference Kroot EJ, de Jong BA, van Leeuwen MA, Swinkels H, van den Hoogen FH, van’t Hof M, van de Putte LB, van Rijswijk MH, van Venrooij WJ, van Riel PL (2000) The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent onset rheumatoid arthritis. Arthritis Rheum 43:1831–1835PubMedCrossRef Kroot EJ, de Jong BA, van Leeuwen MA, Swinkels H, van den Hoogen FH, van’t Hof M, van de Putte LB, van Rijswijk MH, van Venrooij WJ, van Riel PL (2000) The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent onset rheumatoid arthritis. Arthritis Rheum 43:1831–1835PubMedCrossRef
12.
go back to reference Hill JA, Southwood S, Sette A, Jevnikar AM, Bell DA, Cairns E (2003) 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 171:538–541PubMed Hill JA, Southwood S, Sette A, Jevnikar AM, Bell DA, Cairns E (2003) 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 171:538–541PubMed
13.
go back to reference Berglin E, Padyukov L, Sundin U, Hallmans G, Stenlund H, van Venrooij WJ, Klareskog L, Dahlqvist SR (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:R303–R308PubMedCrossRef Berglin E, Padyukov L, Sundin U, Hallmans G, Stenlund H, van Venrooij WJ, Klareskog L, Dahlqvist SR (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:R303–R308PubMedCrossRef
14.
go back to reference Kaltenhäuser S, Pierer M, Arnold S, Kamprad M, Baerwald C, Häntzschel H, Wagner U (2007) Antibodies against cyclic citrullinated peptides are associated with the DRB1 share epitope and predict joint erosion in rheumatoid arthritis. Rheumatology 46:100–104PubMedCrossRef Kaltenhäuser S, Pierer M, Arnold S, Kamprad M, Baerwald C, Häntzschel H, Wagner U (2007) Antibodies against cyclic citrullinated peptides are associated with the DRB1 share epitope and predict joint erosion in rheumatoid arthritis. Rheumatology 46:100–104PubMedCrossRef
15.
go back to reference Mewar D, Coote A, Moore DJ, Marinou I, Keyworth J, Dickson MC, Montgomery DS, Binks MH, Wilson AG (2006) Independent associations of anti-cyclic citrullinated peptide antibodies and rheumatoid factor with radiographic severity of rheumatoid arthritis. Arthritis Res Ther 8:R128PubMedCrossRef Mewar D, Coote A, Moore DJ, Marinou I, Keyworth J, Dickson MC, Montgomery DS, Binks MH, Wilson AG (2006) Independent associations of anti-cyclic citrullinated peptide antibodies and rheumatoid factor with radiographic severity of rheumatoid arthritis. Arthritis Res Ther 8:R128PubMedCrossRef
16.
go back to reference van der Helm-van Mil AH, Verproot KN, Breedveld FC, Huizinga TW, Toes RE, de Vries RR (2006) The HLA-DRB1 shared epitope alleles are primarily a risk factor for anti-cyclic citrullinated peptide antibodies and are not an independent risk factor for development of rheumatoid arthritis. Arthritis Rheum 54:1117–1121 van der Helm-van Mil AH, Verproot KN, Breedveld FC, Huizinga TW, Toes RE, de Vries RR (2006) The HLA-DRB1 shared epitope alleles are primarily a risk factor for anti-cyclic citrullinated peptide antibodies and are not an independent risk factor for development of rheumatoid arthritis. Arthritis Rheum 54:1117–1121
17.
go back to reference Vander Cruyssen B, Hoffman IE, Peene I, Union A, Mielants H, Meheus L, De Keyser F (2007) Prediction models for rheumatoid arthritis during diagnostic investigation: elevation of combinations of rheumatoid factor, anti-citrullinated protein/peptide antibodies and the human leucocyte antigen-shared epitope. Ann Rheum Dis 66:364–369PubMedCrossRef Vander Cruyssen B, Hoffman IE, Peene I, Union A, Mielants H, Meheus L, De Keyser F (2007) Prediction models for rheumatoid arthritis during diagnostic investigation: elevation of combinations of rheumatoid factor, anti-citrullinated protein/peptide antibodies and the human leucocyte antigen-shared epitope. Ann Rheum Dis 66:364–369PubMedCrossRef
18.
go back to reference Bannai M, Tokunaga K, Lin L, Kuwata S, Mazda T, Amaki I, Fujisawa K, Juji T (1994) Discrimination of human HLA-DRB1 alleles by PCR-SSCP (single strand conformation polymorphism) method. Eur J Immunogenet 21:1–9PubMedCrossRef Bannai M, Tokunaga K, Lin L, Kuwata S, Mazda T, Amaki I, Fujisawa K, Juji T (1994) Discrimination of human HLA-DRB1 alleles by PCR-SSCP (single strand conformation polymorphism) method. Eur J Immunogenet 21:1–9PubMedCrossRef
Metadata
Title
Anti-cyclic citrullinated peptide antibody is associated with radiographic erosion in rheumatoid arthritis independently of shared epitope status
Authors
Churl Hyun Im
Eun Ha Kang
Hee Jung Ryu
Jung Hwa Lee
Eun Young Lee
Yun Jong Lee
Eun Bong Lee
Yeong Wook Song
Publication date
01-01-2009
Publisher
Springer-Verlag
Published in
Rheumatology International / Issue 3/2009
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-008-0690-9

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