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 fou
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 fou
复制标题
预防抗瓜氨酸蛋白抗体阳性类风湿性关节炎主要与 HLA-DRB1*1301 相关：对 4 种患者中的 HLA-DRB1 与抗瓜氨酸蛋白抗体阳性和抗瓜氨酸蛋白抗体阴性类风湿性关节炎的关联进行荟萃分析
作者：
D. van der Woude;B. Lie;E. Lundström;A. Balsa;A. Feitsma;J. Houwing;W. Verduijn;Gry B. N. Nordang;L. Alfredsson;L. Klareskog;D. Pascual‐Salcedo;M. González;M. López;Fernando Valero;B. Roep;T. Huizinga;T. Kvien;Javier Martín;L. Padyukov;R. de Vries;R. Toes
客观的
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 control subjects for whom information on HLA-DRB1 typing and ACPA status was available were collected from 4 European countries: Norway, Sweden, The Netherlands, and Spain. The odds ratios (ORs) and 95% confidence intervals (95% CIs) 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 that conveyed protection after stratification for SE were HLA-DRB1*13 alleles (OR 0.54 [95% CI 0.38-0.77]). The protective effect of the allele classifications based on the DERAA and D70 sequences was no longer present after exclusion of DRB1*13 (for D70, OR 0.97 [95% CI 0.75-1.25]), indicating that DRB1*13, rather than the DERAA or D70 sequence as such, is associated with protection. Among the DRB1*13 alleles, only DRB1*1301 was associated with protection (OR 0.24 [95% CI 0.09-0.59]). Protection appeared to follow a north-to-south gradient, with the strongest association in northern European 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 HLA-DRB1*1301.
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影响因子：
9.8
作者：
Kallberg, Henrik;Padyukov, Leonid;Alfredsson, Lars
通讯作者：
Alfredsson, Lars
影响因子：
--
作者：
Hughes, Laura B.;Morrison, Dahliann;Bridges, S. Louis, Jr.
通讯作者：
Bridges, S. Louis, Jr.
影响因子：
--
作者：
Huizinga, TWJ;Amos, CI;Criswell, LA
通讯作者：
Criswell, LA
影响因子：
--
作者：
Gorman, JD;Lum, RF;Criswell, LA
通讯作者：
Criswell, LA