Kanazawa University Graduate School of Medical Sciences and Komatsu Municipal Hospital, Ishikawa, Japan.
Arthritis Care Res (Hoboken). 2014 Apr;66(4):575-84. doi: 10.1002/acr.22163.
To identify and characterize a novel systemic sclerosis (SSc)-related autoantibody directed against a complex consisting of RuvBL1 and RuvBL2 (RuvBL1/2) and to assess its clinical correlations.
We first analyzed 316 consecutive patients with SSc who were evaluated at Kanazawa University Hospital. Controls included 290 patients with other connective tissue diseases, interstitial lung disease alone, or autoimmune hepatitis, and 50 healthy subjects. Autoantibody specificities were analyzed using RNA and protein immunoprecipitation assays. Autoimmune targets were affinity purified using patients' sera and subjected to liquid chromatography mass spectrometry. SSc patients in another institution in Japan and the University of Pittsburgh cohort were also included in analysis for evaluating clinical correlations.
By protein immunoprecipitation assay, 6 SSc sera (1.9%) reacted with doublets with molecular weights of ∼50 kd. Liquid chromatography mass spectrometry of the partially purified autoantigen and additional immunoblot-based analyses revealed that this antibody specificity recognized RuvBL1/2. Anti-RuvBL1/2 antibody was exclusively detected in SSc patients. SSc patients with anti-RuvBL1/2 in both the Japanese and Pittsburgh cohorts consistently had higher frequencies of SSc in overlap with myositis and diffuse skin thickening than those without anti-RuvBL1/2. Compared with other autoantibodies related to SSc/myositis overlap (anti-PM-Scl and anti-Ku), anti-RuvBL1/2 was distinctive in terms of its associations with older age at SSc onset, male sex, and a high frequency of diffuse cutaneous involvement.
Anti-RuvBL1/2 antibody is a novel SSc-related autoantibody associated with a unique combination of clinical features, including myositis overlap and diffuse cutaneous involvement.
鉴定并描述一种针对 RuvBL1 和 RuvBL2 复合物的新型系统性硬化症（SSc）相关自身抗体，并评估其临床相关性。
我们首先分析了在金泽大学医院就诊的 316 例连续 SSc 患者。对照组包括 290 例其他结缔组织疾病、单独间质性肺病或自身免疫性肝炎患者，以及 50 例健康对照。使用 RNA 和蛋白质免疫沉淀检测分析抗体特异性。使用患者的血清对自身免疫靶标进行亲和纯化，并进行液相色谱-质谱分析。还纳入了日本另一家机构和匹兹堡大学队列的 SSc 患者进行分析，以评估临床相关性。
通过蛋白质免疫沉淀检测，6 例 SSc 血清（1.9%）与分子量约为 50 kd 的双体反应。部分纯化的自身抗原的液相色谱-质谱分析和其他免疫印迹分析显示，该抗体特异性识别 RuvBL1/2。抗 RuvBL1/2 抗体仅在 SSc 患者中检测到。在日本和匹兹堡队列中同时具有抗 RuvBL1/2 的 SSc 患者与无抗 RuvBL1/2 的患者相比，SSc 重叠肌炎和弥漫性皮肤增厚的频率更高。与其他与 SSc/肌炎重叠相关的自身抗体（抗 PM-Scl 和抗 Ku）相比，抗 RuvBL1/2 抗体在其与发病年龄较大、男性和弥漫性皮肤受累频率高相关方面具有独特性。
抗 RuvBL1/2 抗体是一种新型 SSc 相关自身抗体，与肌炎重叠和弥漫性皮肤受累等独特的临床特征相关。
