Pedersen Kathrine, Hansen Annette Gudmann, Palarasah Yaseelan, Troldborg Anne, Thiel Steffen
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Scand J Immunol. 2025 Sep;102(3):e70050. doi: 10.1111/sji.70050.
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterised by heterogeneous clinical manifestations and varying degrees of organ involvement. The CD40-CD40 Ligand (CD40L) pathway is implicated in autoimmune responses, with elevated levels of soluble CD40L (sCD40L) observed in SLE patients. This study investigates sCD40L as a biomarker for disease activity and its utility in stratifying patients for CD40L-targeted therapies. Plasma levels of sCD40L were quantified in SLE patients (n = 169) and healthy controls (n = 100). Correlations between sCD40L levels and disease activity measures were analysed using Spearman's correlation and logistic regression. K-means clustering grouped patients based on sCD40L concentrations, and principal component analysis (PCA) was performed to assess relationships among disease activity variables. SLE patients exhibited significantly higher sCD40L levels (median 2.2 ng/mL) than healthy controls (median 0.81 ng/mL; p = 0.0079). Elevated sCD40L levels correlated weakly with higher SLE Disease Activity Index (SLEDAI) scores (p = 0.0418), positive Anti-Nuclear Antibody status (p = 0.0133), increased IgG levels (p = 0.0148) and decreased lymphocyte counts (p = 0.0327). Clustering analysis and PCA revealed that patients with higher sCD40L levels tended to have increased disease activity, elevated anti-dsDNA antibody concentrations, and higher C-reactive protein (CRP) levels. Elevated sCD40L levels in SLE patients correlate with disease activity markers, suggesting its potential as a biomarker for monitoring disease progression and severity. Additionally, sCD40L may aid in stratifying patients who could benefit from CD40L-targeted therapies within a treat-to-target framework. Further longitudinal studies with larger cohorts are warranted to validate and explore the role of sCD40L in personalised SLE treatment strategies.
系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，其临床表现多样，器官受累程度各异。CD40 - CD40配体（CD40L）通路与自身免疫反应有关，在SLE患者中观察到可溶性CD40L（sCD40L）水平升高。本研究调查sCD40L作为疾病活动生物标志物的情况及其在对患者进行CD40L靶向治疗分层中的作用。对169例SLE患者和100例健康对照者的血浆sCD40L水平进行了定量。使用Spearman相关性分析和逻辑回归分析sCD40L水平与疾病活动指标之间的相关性。K均值聚类根据sCD40L浓度对患者进行分组，并进行主成分分析（PCA）以评估疾病活动变量之间的关系。SLE患者的sCD40L水平（中位数2.2 ng/mL）显著高于健康对照者（中位数0.81 ng/mL；p = 0.0079）。sCD40L水平升高与较高的SLE疾病活动指数（SLEDAI）评分（p = 0.0418）、抗核抗体阳性状态（p = 0.0133）、IgG水平升高（p = 0.0148）和淋巴细胞计数降低（p = 0.0327）呈弱相关。聚类分析和PCA显示，sCD40L水平较高的患者往往疾病活动增加、抗双链DNA抗体浓度升高和C反应蛋白（CRP）水平升高。SLE患者sCD40L水平升高与疾病活动标志物相关，表明其作为监测疾病进展和严重程度生物标志物的潜力。此外，sCD40L可能有助于在达标治疗框架内对可能从CD40L靶向治疗中获益的患者进行分层。有必要进行更大样本量的进一步纵向研究，以验证和探索sCD40L在个性化SLE治疗策略中的作用。
