Rheumatology Advance Access published online on June 5, 2008
Rheumatology, doi:10.1093/rheumatology/ken192
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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
1Department of Rheumatology, Rouen University Hospital & Inserm, Institute for Biomedical Research, University of Rouen, Rouen, 2GenHotel, University of Evry-Paris VII, Faculty of Lariboisière-Saint Louis, Evry-Genopole, 3Department of Rheumatology, Paris VII University, Bichat Claude Bernard University Hospital, Paris, 4Immunology Laboratory, Rouen University Hospital & Inserm, Institute for Biomedical Research, University of Rouen, 5Etablissement Français du Sang-Normandie, Rouen and 6Department of Rheumatology, Amiens University Hospital, Amiens, France.
Correspondence to:
V. Goëb, Rheumatology Department & Inserm U905, Rouen University Hospital, 76031 Rouen cedex, France. E-mail: goebvince{at}yahoo.fr
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Abstract |
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Objectives. To evaluate the predictive value of TNFRII 196R, PTPN22 1858T and HLA-shared epitope (SE) alleles, RFs and anti-citrullinated protein antibodies (ACPAs) for RA diagnosis in a cohort of patients with very early arthritis.
Methods. We followed up 284 patients who had swelling of at least two joints that had persisted for longer than 4 weeks but had been evolving for <6 months. At 2 yrs, patients were classified as having RA or non-RA rheumatic diseases according to the ACR criteria. Patients were genotyped with respect to TNFRII 196M/R and PTPN22 1858C/T polymorphisms and HLA-SE. The presence of IgA, IgG and IgM RF isotypes and ACPA was sought in sera collected at disease onset.
Results. HLA-SE alleles alone, concomitant presence of TNFRII 196R and PTPN22 1858T alleles, IgA, IgG and IgM RF alone and ACPA were found to be significantly associated with RA diagnosis. Using logistic regression analysis, the concomitant presence of RF and ACPA at disease onset was the best association to predict RA diagnosis. In patients (n = 34) who did not fulfil the ACR criteria for RA at inclusion but who progressed to ACR positivity, the study of the genetic risk markers did not contribute to predict RA diagnosis at 2 yrs.
Conclusions. PTPN22 1858T, TNFRII 196R and HLA-SE alleles do not improve the predictive value of RF and ACPA for RA diagnosis in our cohort, and do not contribute to an earlier diagnosis in undifferentiated patients initially negative for RF and ACPA.
KEY WORDS: Rheumatoid arthritis, TNFRII, PTPN22, HLA-DRB1, Diagnosis, Autoantibodies, Anti-citrullinated protein antibodies, Rheumatoid factor
Submitted 2 January 2008;
revised version accepted 14 April 2008.
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