Abstract

Introduction

Systemic sclerosis (SSc) is an autoimmune disease caused by the imbalance between the activity of angiotensin II and angiotensin-(1–7). Their balance should be controlled by angiotensin-converting enzyme 2 (ACE2), which degrades angiotensin II into angiotensin-(1–7). Previously, autoantibodies to ACE2 (anti-ACE2) were identified in patients with vasculopathy due to different connective tissue diseases, including SSc, but their frequency in SSc was not further analyzed. The aim of the research was to investigate the prevalence and potential role of those anti-ACE2 antibodies in SSc patients.

Materials and methods

There were enrolled 27 patients with SSc and 23 healthy donors. ELISA assay determined the presence of anti-ACE2 autoantibodies in serum samples. The results were compared to plasma measurements of angiotensin-(1–7) level via commercial ELISA.

Results

The presence of anti-ACE2 autoantibodies was confirmed in five patients with SSc and two healthy controls. Two of those SSc subjects were anti-Scl70+, another two were double anti-Scl70+ and anti-Ro/SSA+, and anti-PM/Scl antibodies were detected in one patient. Median plasma level of Ang-(1–7) in anti-ACE2 negative patients was 47.4 pg/ml and stayed below the detection level in anti-ACE2 positive subjects. The plasma level of Ang-(1–7) was undetectable in four SSc patients, and three of them were anti-ACE2 positive.

Conclusions

Anti-ACE2 antibodies appear to be other functional autoantibodies with the potential to dysregulate the balance between Ang II and Ang-(1–7). They are non-specific for SSc and probably result from polyautoimmunity which affect some of SSc patients. Their occurrence in SSc settings may be associated with a severe depletion of plasma Ang-(1–7).

中文翻译：

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血管紧张素转换酶 2 功能性自身抗体在系统性硬化症患者中的患病率和作用

摘要

介绍

系统性硬化症 (SSc) 是一种由血管紧张素 II 和血管紧张素 (1-7) 的活性失衡引起的自身免疫性疾病。它们的平衡应由血管紧张素转换酶 2 (ACE2) 控制，ACE2 将血管紧张素 II 降解为血管紧张素-(1-7)。此前，在包括 SSc 在内的不同结缔组织疾病引起的血管病变患者中发现了 ACE2（抗 ACE2）自身抗体，但未进一步分析其在 SSc 中的频率。该研究的目的是调查这些抗 ACE2 抗体在 SSc 患者中的普遍性和潜在作用。

材料和方法

共纳入 27 名 SSc 患者和 23 名健康供者。ELISA测定确定血清样品中抗ACE2自身抗体的存在。将结果与通过商业 ELISA 测量的血浆血管紧张素（1-7）水平进行比较。

结果

5 名 SSc 患者和 2 名健康对照者证实存在抗 ACE2 自身抗体。其中两名 SSc 受试者为抗 Scl70+，另外两名为双重抗 Scl70+ 和抗 Ro/SSA+，一名患者检测到抗 PM/Scl 抗体。抗 ACE2 阴性患者的 Ang-(1-7) 中位血浆水平为 47.4 pg/ml，低于抗 ACE2 阳性患者的检测水平。4 名 SSc 患者的血浆 Ang-(1-7) 水平未检测到，其中 3 名抗 ACE2 阳性。

结论

抗 ACE2 抗体似乎是其他功能性自身抗体，可能会失调 Ang II 和 Ang-(1-7) 之间的平衡。它们对 SSc 没有特异性，可能是由影响一些 SSc 患者的多自身免疫引起的。它们在 SSc 环境中的发生可能与血浆 Ang-(1-7) 的严重消耗有关。