Antibodies to Citrullinated α-Enolase Peptide 1 Are Specific for Rheumatoid Arthritis and Cross-React With Bacterial Enolase
Antibodies to Citrullinated α-Enolase Peptide 1 Are Specific for Rheumatoid Arthritis and Cross-React With Bacterial Enolase
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DOI：
10.1002/art.23936
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发表时间：
2008-10-01
影响因子：
--
通讯作者：
Venables, Patrick J.
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文献类型：
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作者：
Lundberg, Karin;Kinloch, Andrew;Venables, Patrick J.
客观的。绘制对人瓜氨酸α-烯醇化酶（类风湿性关节炎 (RA) 候选自身抗原）的抗体反应，并检查与细菌烯醇化酶的交叉反应性。方法。通过酶联免疫吸附测定 (ELISA) 测试从 RA 患者、疾病对照受试者和健康对照受试者获得的血清样品与瓜氨酸 α-烯醇酶肽的反应性。对免疫显性表位具有特异性的抗体是在兔子中产生的或从 RA 血清中纯化的。通过抑制 ELISA 研究与其他瓜氨酸表位的交叉反应性，并通过免疫印迹研究与细菌烯醇化酶的交叉反应性。结果。鉴定出一种免疫显性肽，即瓜氨酸α-烯醇化酶肽 1。在 37-62% 的 RA 患者血清、3% 的疾病对照受试者血清和 2% 的健康对照受试者血清中观察到针对该表位的抗体。同源肽可抑制结合，但含精氨酸的对照肽或分子其他位置的 4 个瓜氨酸化肽不会抑制结合，表明抗体结合依赖于瓜氨酸和侧翼氨基酸。免疫显性肽与牙龈卟啉单胞菌烯醇化酶具有 82% 的同源性，瓜氨酸α-烯醇化酶肽 I 的抗体水平与细菌肽的抗体水平相关（r(2) = 0.803，P < 0.0001）。亲和纯化的人肽抗体与瓜氨酸重组牙龈卟啉单胞菌烯醇酶交叉反应。结论。我们已经鉴定出瓜氨酸α-烯醇化酶中的免疫显性表位，该表位的抗体对 RA 具有特异性。我们关于序列相似性和与细菌烯醇化酶交叉反应性的数据可能表明细菌感染，特别是牙龈卟啉单胞菌感染，在引发一部分 RA 患者的自身免疫方面发挥着作用。
Objective. To map the antibody response to human citrullinated a-enolase, a candidate autoantigen in rheumatoid arthritis (RA), and to examine cross-reactivity with bacterial enolase.Methods. Serum samples obtained from patients with RA, disease control subjects, and healthy control subjects were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with citrullinated a-enolase peptides. Antibodies specific for the immunodominant epitope were raised in rabbits or were purified from RA sera. Cross-reactivity with other citrullinated epitopes was investigated by inhibition ELISAs, and cross-reactivity with bacterial enolase was investigated by immunoblotting.Results. An immunodominant peptide, citrullinated a-enolase peptide 1, was identified. Antibodies to this epitope were observed in 37-62% of sera obtained from patients with RA, 3% of sera obtained from disease control subjects, and 2% of sera obtained from healthy control subjects. Binding was inhibited with homologous peptide but not with the arginine-containing control peptide or with 4 citrullinated peptides from elsewhere on the molecule, indicating that antibody binding was dependent on both citrulline and flanking amino acids. The immunodominant peptide showed 82% homology with enolase from Porphyromonas gingivalis, and the levels of antibodies to citrullinated a-enolase peptide I correlated with the levels of antibodies to the bacterial peptide (r(2) = 0.803, P < 0.0001). Affinity-purified antibodies to the human peptide cross-reacted with citrullinated recombinant P gingivalis enolase.Conclusion. We have identified an immunodominant epitope in citrullinated a-enolase, to which antibodies are specific for RA. Our data on sequence similarity and cross-reactivity with bacterial enolase may indicate a role for bacterial infection, particularly with P gingivalis, in priming autoimmunity in a subset of patients with RA.