Shared Epitope and Anti-Cyclic Citrullinated Peptide Antibodies: Relationship with Age at Onset and Duration of Disease in Rheumatoid Arthritis

Varadé, Jezabel; Loza-Santamaría, Estíbaliz; Fernández‐Arquero, Miguel; Lamas, José Ramón; Figueredo, Maria de los Ángeles; Jover, Juan A.; Concha, Emilio G. de la; Rodríguez, L. Rodríguez; Urcelay, Elena; Fernández‐Gutiérrez, Benjamín; Martínez-Doncel, Alfonso

doi:10.3899/jrheum.080735

Cited by 5 publications

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“…However, an association of anti-CCP antibodies with early RA onset was also found in 468 Swedish patients in whom anti-CCP antibodies were present in 67.9% of them [14]. In a sample of 411 Spanish patients with RA in which 54% were anti-CCP positive, the trend for association observed between anti-CCP antibodies and age at onset disappeared when disease duration was taken into account [15].…”

Section: Discussionmentioning

confidence: 90%

Anti-CCP antibodies are associated with early age at onset in patients with rheumatoid arthritis

et al. 2011

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Section: Discussionmentioning

confidence: 90%

Anti-CCP antibodies are associated with early age at onset in patients with rheumatoid arthritis

et al. 2011

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“…[9][10][11][12] Most studies show no RA susceptibility effect of HLA-DRB1 SE independent of ACPA, 10,[13][14][15] but recently an effect on ACPA-negative RA has been described. 16,17 Furthermore, there may be a hierarchy of risk among HLA-DRB1 SE alleles. Focusing on the 70-74 amino-acid sequence, QKRAA('S 2 ') alleles conferred greater RA susceptibility than the other HLA-DRB1 SE alleles ('S 3P ': QRRAA/RRRAA).…”

Section: Introductionmentioning

confidence: 99%

A spectrum of susceptibility to rheumatoid arthritis within HLA-DRB1: stratification by autoantibody status in a large UK population

et al. 2011

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Previously-proposed rheumatoid arthritis (RA) HLA-DRB1 susceptibility and protective models were compared, based on amino acids at positions 67-74 and autoantibody combinations. 3 657 RA patients and 1 357 controls were studied using logistic regression, with secondary stratification by anti-citrullinated peptide antibodies(ACPA) and rheumatoid factor(RF). Susceptibility models were based on previously defined HLA-DRB1 shared epitope(SE) subgroups. 70 DERAA 74 , D 70 and I 67 protective models were compared, adjusting for HLA-DRB1 SE. A hierarchy of risk was observed within the HLA-DRB1 SE, particularly for ACPA-positive and RF-positive RA: HLA-DRB1*0401B*04044*0101B*1001 (*04044*0101: P ¼ 0.0003). HLA-DRB1*0401/*0404 compound heterozygosity conferred a risk similar to *0401 homozygosity (P ¼ 0.70). Protective effects of D 70 and I 67 were similar. Predictions of the D 70 model fitted the data better than those of the I 67 model. The protective effect of D 70 showed a gene-dose effect (OR 0.82, 95% CI 0.73-0.92, P ¼ 5.8 Â 10 À4 ), but was only seen in RA patients positive for RF or ACPA. HLA-DRB1 SE alleles were also associated with ACPA-negative, RF-positive RA (OR 1.42 (1.15-1.76), P ¼ 0.0012).In conclusion, HLA-DRB1 SE alleles show heterogeneity in RA susceptibility; their major effect appears to be mediated by ACPA positivity, but a significant association of HLA-DRB1 SE with RF-positive, ACPA-negative RA was also observed. D 70 specifically protected against antibody-positive RA.

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Combined influence of genetic and environmental factors in age of rheumatoid arthritis onset

et al. 2011

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To study the combined effect of both genetic and environmental factors in the age of rheumatoid arthritis onset. Patients (n = 507). Shared epitope characterization was performed using Lifecodes HLA-SSO. Genotyping of protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601 and signal transducers and activators of transcription 4 (STAT4) rs7574865 polymorphism was performed using fast real-time PCR System. Shared epitope, antibodies directed against cyclic citrulinated peptide (anti-CCP) antibodies and a higher level of education were associated with a younger age at disease onset (P = 0.033, P = 0.004 and P < 0.0001, respectively). Neither carriers of the minor allele of PTPN22 rs2476601 nor STAT4 rs7574 polymorphisms showed a significant association with a younger age at disease onset (P = 0.355, P = 0.065, respectively). We found an additive effect of the three genetic markers in the age at onset: subjects with three markers were associated with a disease onset 9.56, 8.61, and 6.41 years before than those with none, one, or two genetic markers (P = 0.004, P = 0.006 and P = 0.043, respectively). We also described the additive effect of shared epitope, anti-CCP antibodies, educational level, PTPN22, and STAT4 polymorphisms in age at onset. Patients with two, three, four, or five variables were associated with a significant younger age of disease onset (4.72 [0.05-9.38] years (P = 0.048), 9.56 [4.72-14.40] years (P < 0.0001), 12.74 [6.84-18.64] years (P < 0.0001), and 20.87 [10.40-37.17] years (P < 0.0001)). Risk factors for the development of rheumatoid arthritis are also associated, with an additive effect, with a younger age at disease onset.

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Shared Epitope and Anti-Cyclic Citrullinated Peptide Antibodies: Relationship with Age at Onset and Duration of Disease in Rheumatoid Arthritis

Cited by 5 publications

References 10 publications

Anti-CCP antibodies are associated with early age at onset in patients with rheumatoid arthritis

Anti-CCP antibodies are associated with early age at onset in patients with rheumatoid arthritis

A spectrum of susceptibility to rheumatoid arthritis within HLA-DRB1: stratification by autoantibody status in a large UK population

Combined influence of genetic and environmental factors in age of rheumatoid arthritis onset

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