N.M. van Leeuwen, MD, C.M. Wortel, MSc, C.M. Fehres, PhD, H.U. Scherer, MD, PhD, R.E.M Toes, Professor, MSc, PhD, T.W. Huizinga, Professor, MD, PhD, J.K. de Vries-Bouwstra, MD, PhD, Department of Rheumatology, Leiden University Medical Center;
N.M. van Leeuwen, MD, C.M. Wortel, MSc, C.M. Fehres, PhD, H.U. Scherer, MD, PhD, R.E.M Toes, Professor, MSc, PhD, T.W. Huizinga, Professor, MD, PhD, J.K. de Vries-Bouwstra, MD, PhD, Department of Rheumatology, Leiden University Medical Center.
J Rheumatol. 2021 Mar;48(3):402-409. doi: 10.3899/jrheum.191331. Epub 2020 Jun 1.
Autoreactive antibody responses, including the use of several isotypes of autoantibodies, have been shown to be associated with clinical outcome in several rheumatic autoimmune diseases. The goals of this study were to evaluate whether (1) anticentromere antibody (ACA)- and antitopoisomerase antibody (ATA)-specific isotype expression, and (2) organ involvement are associated with the degree of microangiopathy in systemic sclerosis (SSc).
ACA and ATA IgG, IgM, and IgA levels were measured in baseline serum samples of ACA IgG-positive (+) and ATA IgG+ patients with SSc. The degree of microangiopathy was determined based on nailfold videocapillaroscopy (NVC) images collected at the same point in time. Logistic regression analyses with autoantibodies, clinical characteristics, isotype expression, and ACA and ATA IgG, IgM, and IgA levels as independent variables, and NVC pattern as the dependent variable were performed.
In 164 patients, isotype levels and degree of microangiopathy were evaluated. Logistic regression confirmed the association of the degree of microangiopathy with the presence of digital ulcers (OR 3.07, 95% CI 1.43-6.60), interstitial lung disease (OR 3.41, 95% CI 1.11-10.61), and pulmonary arterial hypertension (OR 5.58, 95% CI 2.05-17.81). ATA positivity was associated with more severe microangiopathy (OR 2.09, 95% CI 1.05-4.13). Patients who expressed solely ACA IgG showed a trend towards less severe microangiopathy compared to patients also expressing ACA IgM and/or IgA. Levels of ACA IgG and ATA IgM were found to be associated with microangiopathy severity.
We observed an association between ACA and ATA responses and the degree of microangiopathy in SSc. These findings might indicate that the breadth of the autoimmune response, as reflected by autoantibody production and microvascular damage, interacts in the pathophysiology of SSc.
自身反应性抗体反应，包括几种自身抗体同种型的使用，已被证明与几种风湿性自身免疫性疾病的临床结果相关。本研究的目的是评估（1）着丝粒抗体（ACA）和拓扑异构酶抗体（ATA）特异性同种型表达，以及（2）器官受累是否与系统性硬化症（SSc）的微血管病变程度相关。
在 ACA IgG 阳性（+）和 ATA IgG+ SSc 患者的基线血清样本中测量 ACA 和 ATA IgG、IgM 和 IgA 水平。微血管病变程度基于同时采集的甲褶毛细血管镜（NVC）图像确定。使用逻辑回归分析，将自身抗体、临床特征、同种型表达以及 ACA 和 ATA IgG、IgM 和 IgA 水平作为自变量，NVC 模式作为因变量。
在 164 名患者中评估了同种型水平和微血管病变程度。逻辑回归证实微血管病变程度与存在手指溃疡（OR 3.07，95%CI 1.43-6.60）、间质性肺病（OR 3.41，95%CI 1.11-10.61）和肺动脉高压（OR 5.58，95%CI 2.05-17.81）相关。ATA 阳性与更严重的微血管病变相关（OR 2.09，95%CI 1.05-4.13）。与仅表达 ACA IgG 的患者相比，也表达 ACA IgM 和/或 IgA 的患者表现出更严重的微血管病变趋势。ACA IgG 和 ATA IgM 水平与微血管病变严重程度相关。
我们观察到 ACA 和 ATA 反应与 SSc 中的微血管病变程度之间存在关联。这些发现可能表明，自身抗体产生和微血管损伤反映的自身免疫反应的广度在 SSc 的病理生理学中相互作用。
