Institute of Immunology, Oslo University Hospital, Oslo, Norway.
Lupus. 2012 Nov;21(13):1412-22. doi: 10.1177/0961203312456751. Epub 2012 Aug 3.
The aim of the present study was to assess the autoantibody profile, dominant clinical symptoms and cluster characteristics of different mixed connective tissue disease (MCTD phenotypes. Two-hundred-and-one patients with MCTD were followed-up longitudinally. Five clinical parameters, Raynaud's phenomenon, pulmonary artery hypertension (PAH), myositis, interstitial lung disease (ILD), erosive arthritis and five auto-antibodies besides anti-U1RNP, antiendothelial cell antibodies (AECA), anti-CCP, anti-cardiolipin (anti-CL), anti-SSA/SSB and IgM rheumatoid factor (RF) were selected for cluster analysis. The mean age of patients was 52.9 ± 12.4 years and the mean follow-up of the disease was 12.5 ± 7.2 years. Patients were classified into three cluster groups. Cluster 1 with 77 patients, cluster 2 with 79 patients and cluster 3 with 45 patients. In cluster 1 the prevalence of PAH (55.8%; p < 0.001), Raynaud's phenomenon (92.2%; p < 0.001) and livedo reticularis (24.6%, p < 0.001) was significantly greater than in cluster 2 and 3. In cluster 2, the incidence of ILD (98.7%; p < 0.001), myositis (77.2%; p < 0.001), and esophageal dysmotility (89.8%; p < 0.001) was significantly greater than that in cluster 1 and 3. In cluster 3, anti-CCP antibodies were present in 31 of 45 patients (68.8%) with erosions. Anti-CCP antibodies were present in 37 of 42 patients (88.0%) with erosions. PAH, angina, venous thrombosis was observed in cluster 1 and pulmonary fibrosis in cluster 2, musculosceletal damage, gastrointestinal symptoms and osteoporotic fractures were most frequent in cluster 3. Cumulative survival assessment indicated cluster 1 patients having the worst prognosis. Cluster analysis is valuable to differentiate among various subsets of MCTD and useful prognostic factor regarding the disease course.
本研究旨在评估不同混合性结缔组织病（MCTD）表型的自身抗体谱、主要临床症状和聚类特征。211 例 MCTD 患者进行了纵向随访。选择 5 个临床参数（雷诺现象、肺动脉高压（PAH）、肌炎、间质性肺病（ILD）、侵蚀性关节炎）和 5 种自身抗体（除抗 U1RNP 外，还包括抗内皮细胞抗体（AECA）、抗环瓜氨酸肽（抗 CCP）、抗心磷脂（抗 CL）、抗 SSA/SSB 和 IgM 类风湿因子（RF））进行聚类分析。患者的平均年龄为 52.9±12.4 岁，疾病的平均随访时间为 12.5±7.2 年。患者分为 3 个聚类组。聚类 1 有 77 例，聚类 2 有 79 例，聚类 3 有 45 例。在聚类 1 中，PAH（55.8%；p<0.001）、雷诺现象（92.2%；p<0.001）和网状青斑（24.6%；p<0.001）的患病率明显高于聚类 2 和 3。在聚类 2 中，ILD（98.7%；p<0.001）、肌炎（77.2%；p<0.001）和食管动力障碍（89.8%；p<0.001）的发生率明显高于聚类 1 和 3。在聚类 3 中，45 例中有 31 例（68.8%）有侵蚀性病变的患者存在抗 CCP 抗体，42 例中有 37 例（88.0%）有侵蚀性病变的患者存在抗 CCP 抗体。PAH、心绞痛、静脉血栓形成见于聚类 1，肺纤维化见于聚类 2，肌肉骨骼损伤、胃肠道症状和骨质疏松性骨折最常见于聚类 3。累积生存评估表明聚类 1 患者的预后最差。聚类分析有助于区分不同的 MCTD 亚型，对疾病过程具有有用的预后因素。
