针对抗瓜氨酸化蛋白抗体阳性类风湿性关节炎的保护作用主要与HLA - DRB1*1301相关：一项对四个欧洲人群中HLA - DRB1与抗瓜氨酸化蛋白抗体阳性及抗瓜氨酸化蛋白抗体阴性类风湿性关节炎相关性的荟萃分析。

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.

作者信息

van der Woude Diane, Lie Benedicte A, Lundström Emeli, Balsa Alejandro, Feitsma Anouk L, Houwing-Duistermaat Jeanine J, Verduijn Willem, Nordang Gry B N, Alfredsson Lars, Klareskog Lars, Pascual-Salcedo Dora, Gonzalez-Gay Miguel A, Lopez-Nevot Miguel A, Valero Fernando, Roep Bart O, Huizinga Tom W J, Kvien Tore K, Martín Javier, Padyukov Leonid, de Vries René R P, Toes René E M

机构信息

Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Arthritis Rheum. 2010 May;62(5):1236-45. doi: 10.1002/art.27366.

DOI:10.1002/art.27366

PMID:20131291

Abstract

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-DRB113 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 DRB113 (for D70, OR 0.97 [95% CI 0.75-1.25]), indicating that DRB113, rather than the DERAA or D70 sequence as such, is associated with protection. Among the DRB113 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.

摘要

目的

人们对HLA - DRB1等位基因对类风湿关节炎（RA）发病的保护作用了解甚少。本研究旨在对4个欧洲人群进行荟萃分析，以调查哪些HLA - DRB1等位基因与抗瓜氨酸化蛋白抗体（ACPA）阳性RA和ACPA阴性RA的保护作用相关。

方法

从挪威、瑞典、荷兰和西班牙这4个欧洲国家收集了超过2800例患者和超过3000例对照受试者的HLA - DRB1分型及ACPA状态信息。在一项聚焦于保护等位基因和分类的联合荟萃分析中，分析了与不同HLA - DRB1等位基因相关的比值比（OR）和95%置信区间（95%CI）。对ACPA阳性RA的分析按共享表位（SE）等位基因进行分层，以校正由于这种关联导致的偏差。

结果

在ACPA阳性RA中，经SE分层后唯一具有保护作用的等位基因是HLA - DRB113等位基因（OR 0.54 [95%CI 0.38 - 0.77]）。排除DRB113后，基于DERAA和D70序列的等位基因分类的保护作用不再存在（对于D70，OR 0.97 [95%CI 0.75 - 1.25]），这表明与保护作用相关的是DRB113，而非DERAA或D70序列本身。在DRB113等位基因中, 只有DRB1*1301与保护作用相关（OR 0.24 [95%CI 0.09 - 0.59]）。保护作用似乎呈现出从北到南的梯度，在北欧国家关联最强。在ACPA阴性RA中，与HLA - DRB1等位基因没有显著关联。