Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden, The Netherlands.
Clin Exp Rheumatol. 2018 Jul-Aug;36 Suppl 113(4):109-117. Epub 2018 Jul 18.
To evaluate the additive value of autoantibodies in identifying systemic sclerosis (SSc) patients with high complication risk.
Patients entering the Combined Care In SSc cohort, Leiden University Medical Centre between April 2009 and May 2016 were included. Subgroups of patients were determined using hierarchical clustering, performed on Principal Component Analysis scores, 1) using baseline data of demographic and clinical variables only and 2) with additional use of antibody status. Disease-risk within subgroups was assessed by evaluating 5-year mortality rates. Clinical and autoantibody characteristics of obtained subgroups were compared.
In total 407 SSc patients were included, of which 91% (n=371) fulfilled ACR/EULAR 2013 criteria for SSc. Prevalences of autoantibodies were: anti-centromere 37%, anti-topoisomerase (ATA) 24%, anti-RNA polymerase III 5%, anti-fibrillarin 4% and anti-Pm/Scl 5%. Clinical cluster analysis identified 4 subgroups, with two subgroups showing higher than average mortality (resp. 17% and 7% vs. total group mortality of 4%). ATA-positivity ranged from 10 to 21% in low-risk groups and from 30 to 49% among high-risk groups. Adding autoantibody status to the cluster process resulted in 5 subgroups with 3 showing higher than average mortality. Still, 22% of ATA- positive patients were clustered into a low-risk subgroup, while the total number of patients stratified to a high-risk subgroup increased.
Autoantibodies only partially contribute to risk-stratification and clinical subsetting in SSc. The current findings confirm that not all ATA-positive patients have worse prognosis and as such, additional biomarkers are needed to guide clinical follow-up in SSc.
评估自身抗体在识别具有高并发症风险的系统性硬化症（SSc）患者中的附加价值。
本研究纳入了 2009 年 4 月至 2016 年 5 月期间莱顿大学医学中心联合护理 SSc 队列中的患者。使用层次聚类，基于主成分分析（PCA）评分，确定了亚组患者，1）仅使用基线人口统计学和临床变量数据，2）额外使用抗体状态。通过评估 5 年死亡率来评估亚组内的疾病风险。比较获得的亚组的临床和自身抗体特征。
共纳入 407 例 SSc 患者，其中 91%（n=371）符合 ACR/EULAR 2013 年 SSc 标准。自身抗体的患病率为：抗着丝点 37%，抗拓扑异构酶（ATA）24%，抗 RNA 聚合酶 III 5%，抗核仁纤维蛋白 4%和抗 PM/Scl 5%。临床聚类分析确定了 4 个亚组，其中 2 个亚组的死亡率高于平均水平（分别为 17%和 7%，而总死亡率为 4%）。ATA 阳性率在低风险组为 10%至 21%，在高风险组为 30%至 49%。将自身抗体状态添加到聚类过程中，产生了 5 个亚组，其中 3 个亚组的死亡率高于平均水平。尽管如此，22%的 ATA 阳性患者被分为低风险亚组，而高风险亚组的患者总数增加。
自身抗体仅部分有助于 SSc 的风险分层和临床亚组化。目前的研究结果证实，并非所有 ATA 阳性患者的预后都较差，因此需要额外的生物标志物来指导 SSc 的临床随访。
