Inova Diagnostics, Inc., San Diego, CA, USA.
Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Autoimmun Rev. 2016 Jul;15(7):776-80. doi: 10.1016/j.autrev.2016.03.016. Epub 2016 Mar 18.
Recently, antibodies directed against peptidyl arginine deiminase 3 and 4 (anti-PAD3/PAD4 antibodies), calcium-dependent enzymes that catalyze the conversion from arginine to citrulline, have been described. Furthermore, antibodies that cross-react between PAD3 and PAD4 cause increased PAD4 activity and consequently correlate with joint damage. This study analyzes the correlation of anti-PAD3 antibodies with joint damage.
To validate the novel chemiluminescent immunoassay (CIA) for the detection of anti-PAD3 antibodies, 20 samples were tested by CIA and by immunoprecipitation (IP). Next, 39 RA patients with available joint erosion score (JES), Total Sharp Score (TSS) and Joint Space Narrowing Score (JSNS) were tested for anti-CCP (using different methods) and anti-PAD3 antibodies by CIA.
Excellent correlation was observed between the CIA and IP for the detection of anti-PAD3 antibodies (rho=0.85, p<0.0001). The median JES of our 39 patients was 14.1 with a standard deviation of 11.5. Anti-PAD3 antibody levels (rho=0.39, 95% CI=0.1-0.6; p=0.0149) were correlated with JES. No correlation was found with TSS and JSNS. In this cohort, ACPA measured using different anti-CCP assays did not correlate with the JES.
In our cohort, anti-PAD3 antibodies correlate with joint erosion score. Therefore, anti-PAD3 antibodies might represent promising markers to predict joint damage in RA patients.
最近,已描述了针对肽基精氨酸脱亚氨酶 3 和 4(抗 PAD3/PAD4 抗体)的抗体,这些抗体是钙依赖性酶,可催化精氨酸转化为瓜氨酸。此外,在 PAD3 和 PAD4 之间发生交叉反应的抗体可导致 PAD4 活性增加,并且与关节损伤相关。本研究分析了抗 PAD3 抗体与关节损伤的相关性。
为了验证用于检测抗 PAD3 抗体的新型化学发光免疫分析(CIA),用 CIA 和免疫沉淀(IP)对 20 个样本进行了测试。接下来,用 CIA 测试了 39 名 RA 患者(可获得关节侵蚀评分(JES)、总 Sharp 评分(TSS)和关节间隙狭窄评分(JSNS))的抗 CCP(使用不同的方法)和抗 PAD3 抗体。
在检测抗 PAD3 抗体时,CIA 与 IP 之间观察到极好的相关性(rho=0.85,p<0.0001)。我们 39 名患者的中位 JES 为 14.1,标准差为 11.5。抗 PAD3 抗体水平(rho=0.39,95%CI=0.1-0.6;p=0.0149)与 JES 相关。与 TSS 和 JSNS 无相关性。在该队列中,使用不同的抗 CCP 检测方法测量的 ACPA 与 JES 不相关。
在我们的队列中,抗 PAD3 抗体与关节侵蚀评分相关。因此,抗 PAD3 抗体可能是预测 RA 患者关节损伤的有前途的标志物。