Independent associations of anti-cyclic citrullinated peptide antibodies and rheumatoid factor with radiographic severity of rheumatoid arthritis

被引:90
作者
Mewar, Devesh
Coote, Annabel
Moore, David J.
Marinou, Ioanna
Keyworth, Jodie
Dickson, Marion C.
Montgomery, Doug S.
Binks, Michael H.
Wilson, Anthony G. [1 ]
机构
[1] Univ Sheffield, Div Genom Med, Sheffield, S Yorkshire, England
[2] GlaxoSmithKline R&D, Stevenage, Herts, England
关键词
D O I
10.1186/ar2017
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Several recent publications have established a strong association between anti-cyclic citrullinated peptide antibody (anti-CCP)-positive rheumatoid arthritis ( RA) and carriage of shared epitope ( SE) alleles. Although anti-CCP have also been associated with more severe RA, the issue of whether this is independent of rheumatoid factor (RF) has not been addressed. To identify associations between RF, anti-CCP, SE status and radiological damage, we studied a large cross- sectional cohort with longstanding RA. Individuals (n = 872) enrolled in the study all fulfilled the American College of Rheumatology criteria for RA, had a minimum disease duration of 3 years, and at least one definite radiographic erosion was present in hands or feet. Radiographs were scored blind at study entry by a single musculoskeletal radiologist using a modified Larsen's score. Anti-CCP and RF levels were determined using enzyme-linked immunosorbent assay, and DRB1 typing was performed using polymerase chain reaction based methodology. Both anti-CCP and RF levels were strongly associated with radiographic severity ( P < 0.0001). In subgroups stratified for both anti-CCP and RF status, evidence of independent associations of both antibodies with radiographic outcome was found ( P < 0.0001). An association of SE alleles with radiographic severity was present only in RF-negative individuals. Anti-CCP positivity was associated with SE status with evidence of a gene-dose effect, most markedly in RF-negative individuals ( P < 0.01). Anti-CCP and RF status are independent severity factors for RA, with SE alleles playing at most a secondary role. Our data support the view that previously described associations between SE and radiological severity, especially in RF-negative patients, may be indirect and due to an association with anti-CCP.
引用
收藏
页数:5
相关论文
共 19 条
[1]   THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS [J].
ARNETT, FC ;
EDWORTHY, SM ;
BLOCH, DA ;
MCSHANE, DJ ;
FRIES, JF ;
COOPER, NS ;
HEALEY, LA ;
KAPLAN, SR ;
LIANG, MH ;
LUTHRA, HS ;
MEDSGER, TA ;
MITCHELL, DM ;
NEUSTADT, DH ;
PINALS, RS ;
SCHALLER, JG ;
SHARP, JT ;
WILDER, RL ;
HUNDER, GG .
ARTHRITIS AND RHEUMATISM, 1988, 31 (03) :315-324
[2]   Phototyping: Comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP) [J].
Bunce, M ;
ONeill, CM ;
Barnardo, MCNM ;
Krausa, P ;
Browning, MJ ;
Morris, PJ ;
Welsh, KI .
TISSUE ANTIGENS, 1995, 46 (05) :355-367
[3]  
El-Gabalawy HS, 1999, ARTHRITIS RHEUM-US, V42, P1696, DOI 10.1002/1529-0131(199908)42:8<1696::AID-ANR19>3.0.CO
[4]  
2-K
[5]   Impact of shared epitope genotype and ethnicity on erosive disease - A meta-analysis of 3,240 rheumatoid arthritis patients [J].
Gorman, JD ;
Lum, RF ;
Chen, JJ ;
Suarez-Almazor, ME ;
Thomson, G ;
Criswell, LA .
ARTHRITIS AND RHEUMATISM, 2004, 50 (02) :400-412
[6]   The shared epitope and severity of rheumatoid arthritis [J].
Gorman, JD ;
Criswell, LA .
RHEUMATIC DISEASE CLINICS OF NORTH AMERICA, 2002, 28 (01) :59-+
[7]  
Harrison B, 1999, ARTHRITIS RHEUM, V42, P2174, DOI 10.1002/1529-0131(199910)42:10<2174::AID-ANR19>3.0.CO
[8]  
2-G
[9]   Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins [J].
Huizinga, TWJ ;
Amos, CI ;
van der Helm-van Mil, AHM ;
Chen, W ;
van Gaalen, FA ;
Jawaheer, D ;
Schreuder, GMT ;
Wener, M ;
Breedveld, FC ;
Ahmad, N ;
Lum, RF ;
de Vries, RRP ;
Gregersen, PK ;
Toes, REM ;
Criswell, LA .
ARTHRITIS AND RHEUMATISM, 2005, 52 (11) :3433-3438
[10]   Regulation of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis - Contrasting effects of HLA-DR3 and the shared epitope alleles [J].
Irigoyen, P ;
Lee, AT ;
Wener, MH ;
Li, WT ;
Kern, M ;
Batliwalla, F ;
Lum, RF ;
Massarotti, E ;
Weisman, M ;
Bombardier, C ;
Remmers, EF ;
Kastner, DL ;
Seldin, MF ;
Criswell, LA ;
Gregersen, PK .
ARTHRITIS AND RHEUMATISM, 2005, 52 (12) :3813-3818