Protection against anti- citrullinated protein antibody- positive rheumatoid arthritis is predominantly associated with hlA-Drb1*1301 A meta-analysis of HLA-DRB1 associations with ACPA- positive and ACPA-negative rheumatoid arthritis in four European populations
نویسندگان
چکیده
objective The protective effect of HLA-DRB1 alleles on the development of rheumatoid arthritis (RA) is poorly understood. We performed a meta-analysis of four European populations to investigate which HLA-DRB1 alleles are associated with protection in anticitrullinated protein antibody (ACPA)-positive and ACPA-negative RA. methods More than 2800 patients and 3000 controls with information on HLA-DRB1 typing and ACPA-status were collected from four European countries: Norway, Sweden, the Netherlands and Spain. The odds ratio’s (ORs) and 95% confidence intervals (CI) associated with the different HLA-DRB1 alleles were analyzed in a combined meta-analysis, focused on protective alleles and classifications. The analysis of ACPA-positive RA was stratified for the shared epitope (SE) alleles to correct for skewing due to this association. results In ACPA-positive RA, the only alleles which conveyed protection after stratification for SE, were HLA-DRB1*13 alleles (OR (95%CI): 0.54 (0.38-0.77)). The protective effect of the allele classifications based on the DERAA and D70 sequence was no longer present after exclusion of DRB1*13 (OR (95%CI) D70: 0.97 (0.75-1.25)), indicating that DRB1*13, rather than the DERAA or D70 sequence as such is associated with protection. Within the DRB1*13 alleles only DRB1*1301 was associated with protection (OR (95%CI): 0.24 (0.09-0.59)). Protection appeared to follow a North-South gradient with the strongest association in Northern countries. In ACPA-negative RA, there were no robust associations with HLA-DRB1 alleles. Conclusion Our data do not support any of the classifications of protective alleles and indicate that protection against ACPA-positive RA is predominantly associated with HLADRB1*1301. Diana vd Woude BW.indd 34 19-01-12 11:37 HLA meta-analysis 35
منابع مشابه
Protection against anti-citrullinated protein antibody-positive rheumatoid arthritis is predominantly associated with HLA-DRB1*1301: a meta-analysis of HLA-DRB1 associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in four European populations.
OBJECTIVE The protective effect of HLA-DRB1 alleles on the development of rheumatoid arthritis (RA) is poorly understood. The aim of this study was to perform a meta-analysis of 4 European populations to investigate which HLA-DRB1 alleles are associated with protection in anti-citrullinated protein antibody (ACPA)-positive RA and ACPA-negative RA. METHODS Data for >2,800 patients and >3,000 c...
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