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Rheumatology Advance Access published online on December 21, 2007
Rheumatology, doi:10.1093/rheumatology/kem343
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Auto-antibodies, HLA and PTPN22: susceptibility markers for rheumatoid arthritis

G. Orozco1, D. Pascual-Salcedo2, M. A. López-Nevot3, T. Cobo4, A. Cabezón2, E. Martín-Mola4, A. Balsa4 and J. Martín1

1Instituto de Parasitología y Biomedicina López Neyra, CSIC, Granada, 2Servicio de Inmunología, Hospital La Paz, Madridm, 3Servicio de Inmunología, Hospital Virgen de las Nieves, Granada and 4Servicio de Reumatología, Hospital La Paz, Madrid, Spain

Correspondence to: J. Martín, Consejo Superior de Investigaciones Científicas, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento s/n, 18100 Armilla, Granada, Spain. E-mail: martin{at}ipb.csic.es


  Abstract

Objective. To analyse the relationship between the presence of auto-antibodies [rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP)], HLA-DRB1 alleles and PTPN22 1858 C/T polymorphism and test the value of their combination as susceptibility markers for rheumatoid arthritis (RA).

Methods. Patients with early arthritis were included. At entry in the cohort or during follow-up, 191 patients fulfilled the criteria for RA and 184 individuals suffered from other arthropathies. RF was measured by nephelometry and anti-CCP antibody by enzyme-linked immunosorbent assay. HLA class II alleles were determined by polymerase chain reaction. Samples were genotyped for PTPN22 1858C/T variants using a TaqMan 5'-allele discrimination assay.

Results. The presence of shared epitope (SE) alleles was strongly associated with anti-CCP and RF-positive RA [P = 7.05 x 10–10, odds ratio (OR) 4.57, 95% confidence interval (CI) 2.76–7.57 and P = 1.68 x 10–6, OR 2.99, 95% CI 1.89–4.74, respectively). The combination of the PTPN22 1858T variant and anti-CCP antibodies gave a high specificity for the disease, and was significantly associated with RA (P = 8.86 x 10–5, OR 10.05, 95% CI 1.88–53.73).

Conclusion. The combination of the T variant of the 1858 polymorphism of the PTPN22 gene in combination with the presence of anti-CCP antibodies, preferentially in a SE-positive individual, is associated with the development of RA.

KEY WORDS: Rheumatoid arthritis, Auto-antibodies, Rheumatoid factor, Cyclic citrullinated peptides, HLA-DRB1, PTPN22 gene, Polymorphism

Submitted 24 July 2007; revised version accepted 19 November 2007.
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V. Goeb, P. Dieude, R. Daveau, M. Thomas-L'Otellier, F. Jouen, F. Hau, P. Boumier, F. Tron, D. Gilbert, P. Fardellone, et al.
Contribution of PTPN22 1858T, TNFRII 196R and HLA-shared epitope alleles with rheumatoid factor and anti-citrullinated protein antibodies to very early rheumatoid arthritis diagnosis
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