Montes Ariana, Perez-Pampin Eva, Calaza Manuel, Gomez-Reino Juan J, Gonzalez Antonio
Instituto de Investigacion Sanitaria and Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
Arthritis Rheum. 2012 Oct;64(10):3102-10. doi: 10.1002/art.34569.
To determine whether the anti-citrullinated vimentin peptide 60-75 (anti-Cit-vimentin) and the immunodominant anti-citrullinated α-enolase peptide 1 (anti-CEP-1) antibodies are associated with subsets of patients with rheumatoid arthritis (RA) independently of the associations between anti-cyclic citrullinated peptide (anti-CCP) antibodies and clinical features of RA.
The 3 antibody types were quantified by enzyme-linked immunosorbent assay (ELISA) in serum samples from 521 patients with RA and 173 healthy controls of Spanish ancestry. Genotypes for HLA-DRB1 alleles and rs2476601 in PTPN22 were available for these patients and controls plus an additional 106 healthy controls. A combined analysis of the 3 antibodies was conducted using stratified contingency tables and logistic regression models.
A differential, particularly strong, and independent association was observed between the presence of anti-Cit-vimentin antibodies and the presence of shared epitope (SE) alleles, specifically in patients carrying 2 SE alleles, and between the presence of anti- Cit-vimentin antibodies and the prevalence of joint erosion. Associations were observed between anti-CEP-1 positivity and the presence of HLA-DRB1 and PTPN22 risk alleles and their additive interaction. These associations were not accounted for by the anti-CCP status.
Our results indicate that the 2 antibodies against citrullinated peptides analyzed in this study add specific information beyond that obtained with the anti-CCP status. They define subgroups of patients with RA in which genetic factors have different weight and there is an observed difference in the prevalence of erosions.
确定抗瓜氨酸波形蛋白肽60 - 75（抗瓜氨酸波形蛋白）和免疫显性抗瓜氨酸α -烯醇化酶肽1（抗CEP - 1）抗体是否与类风湿关节炎（RA）患者亚组相关，且独立于抗环瓜氨酸肽（抗CCP）抗体与RA临床特征之间的关联。
采用酶联免疫吸附测定（ELISA）对521例西班牙裔RA患者和173例健康对照的血清样本中的3种抗体类型进行定量分析。这些患者和对照以及另外106例健康对照可获得HLA - DRB1等位基因和PTPN22中rs2476601的基因型。使用分层列联表和逻辑回归模型对这3种抗体进行联合分析。
观察到抗瓜氨酸波形蛋白抗体的存在与共享表位（SE）等位基因的存在之间存在差异，尤其是强烈且独立的关联，特别是在携带2个SE等位基因的患者中，以及抗瓜氨酸波形蛋白抗体的存在与关节侵蚀的患病率之间存在关联。观察到抗CEP - 1阳性与HLA - DRB1和PTPN22风险等位基因的存在及其加性相互作用之间存在关联。这些关联不能由抗CCP状态来解释。
我们的结果表明，本研究中分析的两种抗瓜氨酸肽抗体提供了超出抗CCP状态所获得信息的特定信息。它们定义了RA患者的亚组，其中遗传因素具有不同的权重，并且在侵蚀患病率方面存在观察到的差异。
