Le Tallec Erwan, Bourg Corentin, Bouzillé Guillaume, Belhomme Nicolas, Le Pabic Estelle, Guillot Stéphanie, Droitcourt Catherine, Perlat Antoinette, Jouneau Stéphane, Sobanski Vincent, Donal Erwan, Lescoat Alain
Department of Internal Medicine and Clinical Immunology, CHU de Rennes, Rennes, France
Department of Cardiology, CHU de Rennes, Rennes, Bretagne, France.
RMD Open. 2025 Apr 9;11(2):e005330. doi: 10.1136/rmdopen-2024-005330.
Systemic lupus erythematosus (SLE), a systemic autoimmune disease with heterogeneous severity, poses a challenge in classifying patients due to its dynamic phenotype. We therefore aimed to identify clinical clusters at diagnosis and at the last available visit to define subgroups with different disease trajectories.
This retrospective study included 278 SLE patients fulfilling the 2019 EULAR/American College of Rheumatology classification criteria. Data were extracted from the patient's medical record, encompassing demographic, clinical and immunological features. Two hierarchical clustering analyses were performed: one at diagnosis and the other at the last available visit based on 23 clinical manifestations. We assessed the distribution of autoantibodies among clusters, and survival analyses compared prognosis using the Cox regression model.
Three symptom clusters were identified at diagnosis and confirmed at the last available visit, with consistent clinical profiles. The largest, clusters 1/1', exhibited early articular (95.3%; p=0.0043) and mucocutaneous (58.7%; p=0.0031) symptoms with the best survival rate. Clusters 2/2' displayed the most severe phenotype, including renal involvement (62.2%; p<0.0001), positivity for anti-DNA (90.0%; p=0.0151) and anti-Sm (34.4%; p<0.0001) autoantibodies, and worse prognosis. Clusters 3/3' exhibited a high proportion of SLE patients fulfilling the definition of mixed connective tissue disease (MCTD) (50.0%; p<0.0001) with anti-U1-RNP 70 kDa autoantibodies (87.5%; p<0.0001). Clusters 1 and 2 remained stable during follow-up, cluster 2 even expanding over time, while over half of cluster 3 patients transitioned to a different subgroup.
We identified a distinct MCTD phenotype within SLE patients, a severe SLE phenotype with poor prognosis, and a third group of SLE patients with lower visceral involvement. Clusters remained stable over time, providing insights into disease progression.
系统性红斑狼疮（SLE）是一种严重程度各异的全身性自身免疫性疾病，因其动态表型，在患者分类方面构成挑战。因此，我们旨在确定诊断时和最后一次可获得随访时的临床聚类，以定义具有不同疾病轨迹的亚组。
这项回顾性研究纳入了278例符合2019年欧洲抗风湿病联盟/美国风湿病学会分类标准的SLE患者。数据从患者病历中提取，包括人口统计学、临床和免疫学特征。进行了两次层次聚类分析：一次在诊断时，另一次在最后一次可获得随访时，基于23种临床表现。我们评估了各聚类中自身抗体的分布，并使用Cox回归模型进行生存分析以比较预后。
诊断时确定了三个症状聚类，并在最后一次可获得随访时得到确认，具有一致的临床特征。最大的聚类1/1'表现出早期关节症状（95.3%；p = 0.0043）和皮肤黏膜症状（58.7%；p = 0.0031），生存率最佳。聚类2/2'表现出最严重的表型，包括肾脏受累（62.2%；p < 0.0001）、抗双链DNA抗体阳性（90.0%；p = 0.0151）和抗Sm抗体阳性（34.4%；p < 0.0001），预后较差。聚类3/3'表现出高比例符合混合性结缔组织病（MCTD）定义的SLE患者（50.0%；p < 0.0001），伴有抗U1-RNP 70 kDa自身抗体（87.5%；p < 0.0001）。聚类1和2在随访期间保持稳定，聚类2甚至随时间扩大，而超过一半的聚类3患者转变为不同的亚组。
我们在SLE患者中确定了一种独特的MCTD表型、一种预后不良的严重SLE表型以及第三组内脏受累程度较低的SLE患者。聚类随时间保持稳定，为疾病进展提供了见解。
