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含常见瓜氨酸化表位的合成人工肽在类风湿关节炎诊断中的作用。

The role of synthetic manufactured peptides containing common citrullinated epitopes in rheumatoid arthritis diagnosis.

机构信息

Sackler Faculty of Medicine, Tel-Aviv University, Israel.

Sackler Faculty of Medicine, Tel-Aviv University, Israel; Department of Medicine 'B', Israel; The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.

出版信息

Clin Immunol. 2019 Feb;199:7-11. doi: 10.1016/j.clim.2018.12.004. Epub 2018 Dec 10.

Abstract

BACKGROUND

Anti-citrullinated peptide antibodies (ACPA) play an important role in rheumatoid arthritis (RA) diagnosis. In our study, we sought to assess the potential diagnostic value of synthetically manufactured peptides that contain epitopes believed to have a pathogenic role in RA.

METHODS

Serum samples from RA patients and healthy controls were obtained. Two synthetic peptides were manufactured containing the common epitopes considered to play a pivotal role in the RA pathogenesis including the antigenic epitopes of filaggrin, beta-fibrinogen, collagen, vimentin and enolase. Three different ELISA kits for citrullinated peptides (namely: CCP3, Cit-ME-Vim and Cit-ME-Eno) were tested and compared. To assess the diagnostic value of the three ELISA tests, for each test the optical densities (OD) were recorded. The statistical power of each test was calculated measuring the area under the curve (AUC) corresponding with each peptide.

RESULTS

Serum levels of ACPA recognized by the commercial CCP3 in RA and healthy controls were 1.31 ± 0.88 optic density units (ODU) and 0.21 ± 0.11 ODU, respectively. Cit-ME-Vim levels were 0.55 ± 0.46 ODU in RA subjects and 0.17 ± 0.182 ODU in healthy controls whereas Cit-ME-Eno was 0.61 ± 0.65 ODU in RA subjects and 0.22 ± 0.20 ODU in healthy controls. AUC results were as follows: CCP3, 0.89 [95%CI 0.75-0.87]; Cit-ME-Vim, 0.76 [95%CI 0.69-0.82]; Cit-ME-Eno, 0.73 [95%CI 0.65-0.79]. Statistical significance for all results was achieved (p < .0001). Sensitivity values for each kit are as follow: CCP3 70.42%; Cit-ME-Vim 63.38%; Cit-ME-Eno 40.85%, and specificity 91% for all tests.

CONCLUSION

Our study supports the presence of an added value for the Cit-ME-Vim peptides in the diagnosis of RA. Further studies are needed to replicate such findings.

摘要

背景

抗瓜氨酸化肽抗体(ACPA)在类风湿关节炎(RA)的诊断中具有重要作用。在我们的研究中,我们旨在评估含有被认为在 RA 发病机制中具有致病作用的表位的合成肽的潜在诊断价值。

方法

收集 RA 患者和健康对照者的血清样本。制造了两种含有常见表位的合成肽,这些表位被认为在 RA 发病机制中起着关键作用,包括 Filaggrin、β-纤维蛋白原、胶原、波形蛋白和烯醇酶的抗原表位。测试并比较了三种用于瓜氨酸肽的不同 ELISA 试剂盒(即:CCP3、Cit-ME-Vim 和 Cit-ME-Eno)。为了评估这三种 ELISA 检测的诊断价值,记录了每个检测的光密度(OD)。通过测量与每种肽对应的曲线下面积(AUC)来计算每个检测的统计功效。

结果

商业 CCP3 识别的 RA 和健康对照者的 ACPA 血清水平分别为 1.31±0.88 光密度单位(ODU)和 0.21±0.11 ODU。RA 患者的 Cit-ME-Vim 水平为 0.55±0.46 ODU,健康对照者为 0.17±0.182 ODU,而 RA 患者的 Cit-ME-Eno 水平为 0.61±0.65 ODU,健康对照者为 0.22±0.20 ODU。AUC 结果如下:CCP3,0.89[95%CI 0.75-0.87];Cit-ME-Vim,0.76[95%CI 0.69-0.82];Cit-ME-Eno,0.73[95%CI 0.65-0.79]。所有结果均具有统计学意义(p<0.0001)。每个试剂盒的灵敏度值如下:CCP3,70.42%;Cit-ME-Vim,63.38%;Cit-ME-Eno,40.85%,所有检测的特异性均为 91%。

结论

我们的研究支持 Cit-ME-Vim 肽在 RA 诊断中的附加价值。需要进一步的研究来复制这些发现。

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