HLA - DRB1共享表位等位基因主要是抗环瓜氨酸肽抗体的一个风险因素，而非类风湿关节炎发病的独立风险因素。

The HLA-DRB1 shared epitope alleles are primarily a risk factor for anti-cyclic citrullinated peptide antibodies and are not an independent risk factor for development of rheumatoid arthritis.

作者信息

van der Helm-van Mil Annette H M, Verpoort Kirsten N, Breedveld Ferdinand C, Huizinga Tom W J, Toes René E M, de Vries René R P

机构信息

Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Arthritis Rheum. 2006 Apr;54(4):1117-21. doi: 10.1002/art.21739.

DOI:10.1002/art.21739

PMID:16572446

Abstract

OBJECTIVE

The shared epitope (SE)-containing HLA-DRB1 alleles represent the most significant genetic risk factor for rheumatoid arthritis (RA). Recent studies indicate that the SE alleles are associated with only RA that is characterized by the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies, and not with anti-CCP-negative disease. In this study we investigated whether the SE alleles contribute to the development of anti-CCP-positive RA, or whether they are associated solely with the presence of anti-CCP antibodies. We therefore determined the influence of the SE alleles and anti-CCP antibodies on the progression from recent-onset undifferentiated arthritis (UA) to RA.

METHODS

Patients with recent-onset UA at the 2-week visit (n=570) were selected from the Leiden Early Arthritis Cohort. SE alleles, rheumatoid factor (RF) status, and anti-CCP antibody levels were determined. Progression to RA or other diagnoses was monitored.

RESULTS

One hundred seventy-seven patients with UA developed RA during the 1-year followup, whereas the disease in 393 patients remained unclassified or was given other diagnoses. The SE alleles correlated with the presence of anti-CCP antibodies, but not with the presence of RF. Both in SE-positive and in SE-negative patients with UA, the presence of anti-CCP antibodies was significantly associated with the development of RA. More intriguingly, however, no apparent contribution of the SE alleles to the progression to RA was found when analyses were stratified according to the presence of anti-CCP antibodies. In patients with anti-CCP-positive disease, the presence of SE alleles was associated with significantly higher levels of anti-CCP antibodies, suggesting that the SE alleles act as classic immune response genes.

CONCLUSION

The SE alleles do not independently contribute to the progression to RA from UA, but rather contribute to the development of anti-CCP antibodies.

摘要

目的

含有共同表位（SE）的人类白细胞抗原-DRB1等位基因是类风湿关节炎（RA）最重要的遗传风险因素。最近的研究表明，SE等位基因仅与以抗环瓜氨酸肽（抗CCP）抗体阳性为特征的RA相关，而与抗CCP抗体阴性的疾病无关。在本研究中，我们调查了SE等位基因是否促成抗CCP抗体阳性RA的发生发展，或者它们是否仅与抗CCP抗体的存在相关。因此，我们确定了SE等位基因和抗CCP抗体对近期发病的未分化关节炎（UA）进展为RA的影响。

方法

从莱顿早期关节炎队列中选取在2周随访时近期发病的UA患者（n = 570）。测定SE等位基因、类风湿因子（RF）状态和抗CCP抗体水平。监测疾病进展为RA或其他诊断的情况。

结果

177例UA患者在1年随访期间发展为RA，而393例患者的疾病仍未分类或被给予其他诊断。SE等位基因与抗CCP抗体的存在相关，但与RF的存在无关。在SE阳性和SE阴性的UA患者中，抗CCP抗体的存在均与RA的发生显著相关。然而，更有趣的是，当根据抗CCP抗体的存在进行分层分析时，未发现SE等位基因对进展为RA有明显贡献。在抗CCP抗体阳性疾病患者中，SE等位基因的存在与抗CCP抗体水平显著升高相关，表明SE等位基因起着经典免疫反应基因的作用。