Van Beusecum Justin, McCrorey Marice, Butler Helen, Lacey Ryan, Semenikhina Marharyta, Colvert C, Hawkins Kennedy, Palygin Oleg, Ergul Adviye, Cunningham Melissa, Oates Jim
Medical University of South Carolina and Ralph H. Johnson VAHS.
Medical University of South Carolina.
Res Sq. 2025 Apr 23:rs.3.rs-6465543. doi: 10.21203/rs.3.rs-6465543/v1.
Patients with systemic lupus erythematosus (SLE) are at increased risk of hypertension (HTN) and cardiovascular disease, yet the immunologic drivers of this endothelial and vascular dysfunction remain incompletely understood. Here, we investigate whether autoantibodies targeting endothelin receptors are associated with an SLE diagnosis, elevated blood pressure, and endothelial activation. In two independent clinical cohorts (n = 214), we quantified anti-endothelin receptor A (ETR) and endothelin receptor B (ETR) autoantibodies and additionally quantified soluble vascular adhesion molecule-1 (sVCAM-1) and intracellular adhesion molecule-1 (sICAM-1) as markers of endothelial activation. In both independent cohorts, we report significantly elevated anti-ETR autoantibodies, anti-ETR autoantibodies, and sVCAM-1 in individuals with SLE compared to controls. Anti-ETR autoantibodies, Anti-ETR autoantibodies, and sVCAM-1 levels were significantly increased in SLE subjects independent of HTN status. Anti-ETR autoantibodies correlated positively with systolic and diastolic blood pressure, sVCAM-1, sICAM-1, and anti-ETR autoantibodies. These findings identify a novel immunological signature of endothelial dysfunction in SLE and implicate anti-endothelin receptor autoantibodies as potential biomarkers and therapeutic targets in SLE and its associated HTN.
系统性红斑狼疮（SLE）患者患高血压（HTN）和心血管疾病的风险增加，然而这种内皮和血管功能障碍的免疫驱动因素仍未完全明确。在此，我们研究靶向内皮素受体的自身抗体是否与SLE诊断、血压升高和内皮激活相关。在两个独立的临床队列（n = 214）中，我们对抗内皮素受体A（ETR）和内皮素受体B（ETR）自身抗体进行了定量，并额外对可溶性血管黏附分子-1（sVCAM-1）和细胞间黏附分子-1（sICAM-1）进行了定量，作为内皮激活的标志物。在两个独立队列中，我们报告称，与对照组相比，SLE患者的抗ETR自身抗体、抗ETR自身抗体和sVCAM-1显著升高。抗ETR自身抗体、抗ETR自身抗体和sVCAM-1水平在SLE患者中显著升高，与HTN状态无关。抗ETR自身抗体与收缩压和舒张压、sVCAM-1、sICAM-1以及抗ETR自身抗体呈正相关。这些发现确定了SLE中内皮功能障碍的一种新的免疫特征，并表明抗内皮素受体自身抗体可能是SLE及其相关HTN的生物标志物和治疗靶点。
