Interpretation of an Extended Autoantibody Profile in a Well-Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis
Interpretation of an Extended Autoantibody Profile in a Well-Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis
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DOI：
10.1002/art.39316
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发表时间：
2015-12-01
影响因子：
13.3
通讯作者：
Walker, J. G.
中科院分区：
文献类型：
--
作者：
Patterson, K. A.;Roberts-Thomson, P. J.;Walker, J. G.
Objective.在一个特征明确的澳大利亚患者群中，确定系统性硬化症（SSc）相关自身抗体之间的关系及其临床相关性。用商业免疫分析法分析了505名澳大利亚SSc患者的血清（EuroLine; Euroimmun）用于针对着丝粒蛋白CENP-A和CENP-B的自身抗体，RNA聚合酶III（第三区域行动方案;表位11和155），90-kd核仁蛋白NOR-90，原纤维蛋白，Th/To，PM/Scl-75，PM/Scl-100，Ku，拓扑异构酶I（topo I），三重基序蛋白21/Ro 52和血小板衍生生长因子受体。通过定量自身抗体评分的主成分分析的前2个维度的分层聚类确定患者亚组。并与临床资料进行比较。505例患者中共有449例通过免疫印迹法检测到至少1种自身抗体阳性。自身抗体评分的热图可视化，沿着主成分分析聚类，证明了CENP、RNAP III和拓扑I之间强的互斥关系。确定了五个患者群：CENP、RNAP III强、RNAP III弱、拓扑I和其他。与CENP、RNAP III和拓扑I相关的临床特征与先前发表的关于局限性皮肤和弥漫性皮肤SSc的报告一致。一个新的发现是RNAP III的统计分离成2簇。RNAP III强集群中的患者胃窦血管扩张的风险增加，但食管动力障碍的风险较低。另一组患者更可能是男性，有吸烟史和恶性肿瘤史，但不太可能有毛细血管扩张，雷诺现象和关节挛缩。在澳大利亚SSc患者中确定了五个具有特定临床和血清学相关性的主要自身抗体簇。使用自身抗体的亚类和疾病分层可能具有临床实用性，特别是在早期疾病中。
Objective. To determine the relationships between systemic sclerosis (SSc)-related autoantibodies, as well as their clinical associations, in a well-characterized Australian patient cohort.Methods. Serum from 505 Australian SSc patients were analyzed with a commercial line immunoassay (EuroLine; Euroimmun) for autoantibodies to centromere proteins CENP-A and CENP-B, RNA polymerase III (RNAP III; epitopes 11 and 155), the 90-kd nucleolar protein NOR-90, fibrillarin, Th/To, PM/Scl-75, PM/Scl-100, Ku, topoisomerase I (topo I), tripartite motif-containing protein 21/Ro 52, and platelet-derived growth factor receptor. Patient subgroups were identified by hierarchical clustering of the first 2 dimensions of a principal components analysis of quantitative autoantibody scores. Results were compared with detailed clinical data.Results. A total of 449 of the 505 patients were positive for at least 1 autoantibody by immunoblotting. Heatmap visualization of autoantibody scores, along with principal components analysis clustering, demonstrated strong, mutually exclusive relationships between CENP, RNAP III, and topo I. Five patient clusters were identified: CENP, RNAP III strong, RNAP III weak, topo I, and other. Clinical features associated with CENP, RNAP III, and topo I were consistent with previously published reports concerning limited cutaneous and diffuse cutaneous SSc. A novel finding was the statistical separation of RNAP III into 2 clusters. Patients in the RNAP III strong cluster had an increased risk of gastric antral vascular ectasia, but a lower risk of esophageal dysmotility. Patients in the other cluster were more likely to be male and to have a history of smoking and a history of malignancy, but were less likely to have telangiectasia, Raynaud's phenomenon, and joint contractures.Conclusion. Five major autoantibody clusters with specific clinical and serologic associations were identified in Australian SSc patients. Subclassification and disease stratification using autoantibodies may have clinical utility, particularly in early disease.