From the Department of Microbiology and Immunology, and the Department of Medicine/Rheumatology, The University of Western Ontario, London, Ontario, Canada.
P. Lac, BSc, Department of Microbiology and Immunology, The University of Western Ontario; M. Racapé, PhD, Paris Descartes University and Hôpital Necker, AP-HP, Paris, France; L. Barra, MD, Department of Microbiology and Immunology, and Department of Medicine/Rheumatology, The University of Western Ontario; D.A. Bell, MD, Department of Medicine/Rheumatology, The University of Western Ontario; E. Cairns, PhD, Department of Microbiology and Immunology, and Department of Medicine/Rheumatology, The University of Western Ontario.
J Rheumatol. 2018 Mar;45(3):302-309. doi: 10.3899/jrheum.170446. Epub 2017 Dec 1.
Antibodies that target citrullinated protein/peptide (ACPA) and homocitrullinated/carbamylated protein/peptide (AHCPA) are associated with rheumatoid arthritis (RA). The relationship between ACPA and AHCPA remains unclear. We examined the expression and cross-reactivity of these antibodies using citrulline- and homocitrulline-containing synthetic peptides, CitJED and HomoCitJED, respectively, which have equal numbers of citrulline or homocitrulline residues on the same peptide backbone.
Serum from healthy subjects (n = 51) and patients with RA (n = 137), systemic lupus erythematosus (SLE; n = 37), and psoriatic arthritis (PsA; n = 37) were screened for IgG anti-CitJED and anti-HomoCitJED antibodies by ELISA. Cross-reactivity of these antibodies was examined by inhibition with various concentrations of CitJED and HomoCitJED.
Out of 137 patients with RA, antibodies to CitJED and HomoCitJED were detected in 69 (50%) and 78 (57%), respectively. Anti-CitJED and HomoCitJED antibodies were 77% concordant and their levels were strongly correlated [Spearman correlation coefficient (r) = 0.6676]. Sera from 25/27 patients (93%) with RA were inhibited by both CitJED and HomoCitJED with equal or higher affinity for the cognate (homologous) peptide.
Antibodies to CitJED and HomoCitJED frequently occurred in RA, but were not found in SLE or PsA, suggesting that these antibodies are specific to RA. Cross-reactivity between anti-HomoCitJED and anti-CitJED antibodies suggests that ACPA and AHCPA are derived from the same B cell population and both may contribute to the pathogenesis of RA.
针对瓜氨酸化蛋白/肽（ACPA）和同型瓜氨酸化/氨甲酰化蛋白/肽（AHCPA）的抗体与类风湿关节炎（RA）相关。ACPA 和 AHCPA 之间的关系尚不清楚。我们使用含有瓜氨酸和同型瓜氨酸的合成肽 CitJED 和 HomoCitJED 分别检测了这些抗体的表达和交叉反应性，这两种肽在相同的肽骨架上具有相同数量的瓜氨酸或同型瓜氨酸残基。
通过 ELISA 筛选来自健康受试者（n = 51）和 RA 患者（n = 137）、系统性红斑狼疮（SLE；n = 37）和银屑病关节炎（PsA；n = 37）的血清中的 IgG 抗 CitJED 和抗 HomoCitJED 抗体。通过用各种浓度的 CitJED 和 HomoCitJED 进行抑制来检查这些抗体的交叉反应性。
在 137 名 RA 患者中，检测到 69 名（50%）和 78 名（57%）患者存在针对 CitJED 和 HomoCitJED 的抗体。抗 CitJED 和 HomoCitJED 抗体具有 77%的一致性，并且它们的水平呈强相关性[Spearman 相关系数（r）= 0.6676]。来自 27 名（93%）RA 患者的血清均被 CitJED 和 HomoCitJED 抑制，对同源（同源）肽具有相等或更高的亲和力。
在 RA 中经常发现针对 CitJED 和 HomoCitJED 的抗体，但在 SLE 或 PsA 中未发现，表明这些抗体是 RA 的特异性抗体。抗 HomoCitJED 与抗 CitJED 抗体之间的交叉反应性表明 ACPA 和 AHCPA 来自相同的 B 细胞群体，两者都可能有助于 RA 的发病机制。
