Abstract

Objectives

Autoimmune antibody profiling plays a prominent role in both classification and prognosis of systemic sclerosis (SSc). In the last years novel autoantibodies have been discovered and have become available in diagnostic assays. However, standardization in autoimmune serology is lacking, which may have a negative impact on the added value of autoantibodies in diagnosis and prognosis of SSc. In this paper we describe the comparison of commercially available diagnostic assays for the detection of SSc-associated autoantibodies and explored the coexistence of multiple SSc-associated autoantibodies within patients.

Methods

Serum samples of 347 patients from the Nijmegen Systemic Sclerosis Cohort were included in this study. All patients fulfilled the ACR/EULAR 2013 classification criteria for SSc and were classified as DcSSc or LcSSc according to the Leroy and Medsger criteria. All samples were evaluated on standard laboratory diagnostic tests for detection of SSc-specific autoantibodies CENPA and CENPB (ACA), Scl-70 (ATA), RNA Polymerase III (rp11/155) (ARA), and SSc-associated autoantibodies Fibrillarin, Th-To, PM-scl75, PM-Scl100, RNP68/A/C, Ku, NOR90, and PDGFR from suppliers EUROIMMUN, D-tek and Thermo Fisher Scientific.

Results

We found that 79% of the patients was positive for one or more of the SSc autoantibodies. Overall, a high agreement was observed between the diagnostic methods for the SSC-specific autoantibodies listed in the ACR/EULAR criteria (ATA, ACA, and ARA) (Cohen's kappa 0.53–0.97). However, a lower agreement was found for SSc-associated autoantibodies PM-Scl, and Ku, as well as for the SSc-specific autoantibodies fibrillarin and Th-To. Furthermore, the data revealed that the presence of ATA, ARA and ACA is predominantly mutually exclusive, with only a fraction of the patients testing positive for both ATA and ARA.

Conclusion

Our data showed high concordance of prevalent SSc-specific autoantibodies between different diagnostic assays. Further standardisation for low prevalent SSc-specific and SSc-associated autoantibodies is needed.

中文翻译：

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系统性硬化症中的自身抗体谱；诊断测试的比较

摘要

目标

自身免疫性抗体分析在系统性硬化症 (SSc) 的分类和预后中起着重要作用。在过去的几年中，新的自身抗体被发现并用于诊断分析。然而，自身免疫血清学缺乏标准化，这可能对自身抗体在 SSc 诊断和预后中的附加值产生负面影响。在本文中，我们描述了用于检测 SSc 相关自身抗体的市售诊断测定的比较，并探讨了患者体内多种 SSc 相关自身抗体的共存。

方法

本研究包括来自奈梅亨系统性硬化症队列的 347 名患者的血清样本。所有患者均符合 ACR/EULAR 2013 的 SSc 分类标准，并根据 Leroy 和 Medsger 标准被分类为 DcSSc 或 LcSSc。所有样本均在标准实验室诊断测试中进行评估，以检测 SSc 特异性自身抗体 CENPA 和 CENPB (ACA)、Scl-70 (ATA)、RNA 聚合酶 III (rp11/155) (ARA) 和 SSc 相关自身抗体 Fibrillarin、Th -来自供应商 EUROIMMUN、D-tek 和 Thermo Fisher Scientific 的 PM-scl75、PM-Scl100、RNP68/A/C、Ku、NOR90 和 PDGFR。

结果

我们发现 79% 的患者对一种或多种 SSc 自身抗体呈阳性。总体而言，在 ACR/EULAR 标准（ATA、ACA 和 ARA）中列出的 SSC 特异性自身抗体的诊断方法之间观察到高度一致（Cohen's kappa 0.53–0.97）。然而，发现 SSc 相关自身抗体 PM-Scl 和 Ku 以及 SSc 特异性自身抗体 fibrillarin 和 Th-To 的一致性较低。此外，数据显示 ATA、ARA 和 ACA 的存在主要是相互排斥的，只有一小部分患者的 ATA 和 ARA 检测均呈阳性。

结论

我们的数据显示，不同诊断测定之间普遍存在的 SSc 特异性自身抗体具有高度一致性。需要进一步标准化低流行的 SSc 特异性和 SSc 相关自身抗体。