Phenotypic subgroup in serologically active clinically quiescent systemic lupus erythematosus: A cluster analysis based on CSTAR cohort.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Med Pub Date : 2024-10-11 Epub Date: 2024-07-10 DOI:10.1016/j.medj.2024.06.005

Yufang Ding, Yangzhong Zhou, Feng Zhan, Jian Xu, Xinwang Duan, Hui Luo, Cheng Zhao, Min Yang, Rui Wu, Lijun Wu, Zhen Chen, Wei Wei, Can Huang, Chanyuan Wu, Shangzhu Zhang, Nan Jiang, Dong Xu, Xiaomei Leng, Qian Wang, Xinping Tian, Mengtao Li, Xiaofeng Zeng, Jiuliang Zhao

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Abstract

Background: Serologically active clinically quiescent (SACQ) is a state within systemic lupus erythematosus (SLE) characterized by elevated serologic markers without clinical activity. The heterogeneity in SACQ patients poses challenges in disease management. This multicenter prospective study aimed to identify distinct SACQ subgroups and assess their utility in predicting organ damage.

Methods: SACQ was defined as a sustained period of at least 6 months with persistent serologic activity, marked by positive anti-double-stranded DNA (dsDNA) antibodies and/or hypocomplementemia, and without clinical activity. Cluster analysis was employed, utilizing 16 independent components to delineate phenotypes.

Findings: Among the 4,107 patients with SLE, 990 (24.1%) achieved SACQ within 2.0 ± 2.3 years on average. Over a total follow-up of 7,105.1 patient years, 340 (34.3%) experienced flares, and 134 (13.5%) developed organ damage. Three distinct SACQ subgroups were identified. Cluster 1 (n = 219, 22.1%) consisted predominantly of elderly males with a history of major organ involvement at SLE diagnosis, showing the highest risk of severe flares (16.4%) and organ damage (27.9%). Cluster 2 (n = 279, 28.2%) was characterized by milder disease and a lower risk of damage accrual (5.7%). Notably, 86 patients (30.8%) in cluster 2 successfully discontinued low-dose glucocorticoids, with 49 of them doing so without experiencing flares. Cluster 3 (n = 492, 49.7%) featured the highest proportion of lupus nephritis and a moderate risk of organ damage (11.8%), with male patients showing significantly higher risk of damage (hazard ratio [HR] = 4.51, 95% confidence interval [CI], 1.82-11.79).

Conclusion: This study identified three distinct SACQ clusters, each with specific prognostic implications. This classification could enhance personalized management for SACQ patients.

Funding: This work was funded by the National Key R&D Program (2021YFC2501300), the Beijing Municipal Science & Technology Commission (Z201100005520023), the CAMS Innovation Fund (2021-I2M-1-005), and National High-Level Hospital Clinical Research Funding (2022-PUMCH-D-009).

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血清学活跃的临床静止型系统性红斑狼疮的表型亚群：基于CSTAR队列的聚类分析。

背景：血清学活跃临床静止期（SACQ）是系统性红斑狼疮（SLE）的一种状态，其特点是血清学标志物升高而无临床活动。SACQ患者的异质性给疾病管理带来了挑战。这项多中心前瞻性研究旨在确定不同的SACQ亚组，并评估它们在预测器官损害方面的效用：SACQ定义为持续至少6个月的持续血清学活动，以抗双链DNA（dsDNA）抗体阳性和/或低补体血症为标志，且无临床活动。研究采用聚类分析，利用 16 个独立成分来划分表型：在4107名系统性红斑狼疮患者中，990人（24.1%）平均在2.0 ± 2.3年内达到SACQ。在总共 7105.1 年的随访中，340 名患者（34.3%）病情复发，134 名患者（13.5%）出现器官损伤。我们发现了三个不同的 SACQ 亚群。第一组（n = 219，22.1%）主要由老年男性组成，他们在确诊系统性红斑狼疮时有主要器官受累的病史，出现严重复发（16.4%）和器官损伤（27.9%）的风险最高。第2组（n = 279，28.2%）的特点是病情较轻，受损风险较低（5.7%）。值得注意的是，第 2 组中有 86 名患者（30.8%）成功停用了小剂量糖皮质激素，其中 49 人停药后病情没有复发。第3组（n = 492，49.7%）狼疮肾炎的比例最高，器官损害的风险为中度（11.8%），男性患者的损害风险明显更高（危险比[HR] = 4.51，95%置信区间[CI]，1.82-11.79）：本研究确定了三个不同的 SACQ 群组，每个群组都有特定的预后影响。这一分类可加强对 SACQ 患者的个性化管理：本研究得到了国家重点研发计划（2021YFC2501300）、北京市科委（Z201100005520023）、CAMS创新基金（2021-I2M-1-005）和国家高水平医院临床研究基金（2022-PUMCH-D-009）的资助。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.