Department of Internal Medicine and Clinical Immunology, Regional Competence Center for Systemic and Autoimmune Rare Diseases, Nancy University Hospital, Lorraine University, Vandoeuvre-lès-Nancy, France.
Department of Internal Medicine and Clinical Immunology, Regional Competence Center for Systemic and Autoimmune Rare Diseases, Nancy University Hospital, Lorraine University, Vandoeuvre-lès-Nancy, France; UMR 7365, IMoPA, Lorraine University, CNRS, Nancy, France.
Eur J Intern Med. 2021 Sep;91:45-52. doi: 10.1016/j.ejim.2021.04.020. Epub 2021 May 8.
Clinical significance of anti-Ro52 antibodies in connective tissue diseases (CTD) is controversial. Anti-Ro52 antibodies might be associated with a more severe CTD phenotype, especially interstitial lung disease (ILD). The aims of this study were to evaluate ILD prevalence and severity, the prevalence of micro- or macroangiopathy and CTD-associated cancers in CTD with anti-Ro52 antibodies.
CTD patients with anti-Ro52 antibody screening by immunoblot at diagnosis were enrolled. Two groups were retrospectively formed according to the presence of anti-Ro52 antibodies with an unbiased 1:1 matching on CTD types. Unsupervised multiple correspondence analysis and hierarchical clustering analysis were used to aggregate anti-Ro52 positive patients in subgroups.
408 CTD patients were included. Anti-Ro52 antibodies were detected in 33 % of CTD patients. Anti-Ro52 antibodies were associated with ILD at CTD diagnosis (47.8% vs. 23.0%, OR 3.3 95% IC 1.4 to 8.0, p = 0.008), even after adjusting for the presence of anti-Ro60 antibodies, especially in patients with antisynthetase syndrome, primary Sjögren syndrome and systemic sclerosis. Micro- or macroangiopathy was more frequent in anti-Ro52 positive CTD patients (18.6% vs. 9.7%, p = 0.02) and CTD patients with anti-Ro52 antibodies experienced more frequent relapses and required more immunosuppressive drugs. Clusters 4 and 5 identified anti-Ro52 positive CTD patients with severe ILD and with clinical features of systemic sclerosis or antisynthetase syndrome respectively.
We found that anti-Ro52 antibodies were independently associated with ILD in CTD patients irrespective of CTD type. Anti-Ro52 antibodies could be associated with severity and a more relapsing disease course in CTD patients.
抗 Ro52 抗体在结缔组织病(CTD)中的临床意义存在争议。抗 Ro52 抗体可能与更严重的 CTD 表型相关,尤其是间质性肺病(ILD)。本研究旨在评估抗 Ro52 抗体阳性 CTD 患者的ILD 患病率和严重程度、微或大血管病变及 CTD 相关癌症的患病率。
对诊断时通过免疫印迹筛查出抗 Ro52 抗体的 CTD 患者进行了回顾性研究。根据有无抗 Ro52 抗体,将患者分为两组,比例为 1:1,并对 CTD 类型进行了无偏匹配。采用无监督多对应分析和层次聚类分析将抗 Ro52 阳性患者聚集成亚组。
共纳入 408 例 CTD 患者。33%的 CTD 患者检测到抗 Ro52 抗体。抗 Ro52 抗体与 CTD 诊断时的ILD 相关(47.8%比 23.0%,OR 3.3,95%CI 1.4 至 8.0,p=0.008),即使在调整抗 Ro60 抗体的情况下也是如此,特别是在抗合成酶综合征、原发性干燥综合征和系统性硬化症患者中。抗 Ro52 阳性 CTD 患者微或大血管病变更为常见(18.6%比 9.7%,p=0.02),且抗 Ro52 阳性 CTD 患者更常复发,需要更多的免疫抑制剂。聚类 4 和 5 分别确定了抗 Ro52 阳性 CTD 患者ILD 严重,以及分别具有系统性硬化症或抗合成酶综合征临床特征的患者。
我们发现抗 Ro52 抗体与 CTD 患者的ILD 独立相关,而与 CTD 类型无关。抗 Ro52 抗体可能与 CTD 患者的严重程度和更易复发的病程相关。