Endothelin Receptor Autoantibodies as Emerging Biomarkers and Therapeutic Targets in the Cardiovascular Complications of Lupus

TL;DR

The study finds that autoantibodies targeting endothelin receptors are linked to lupus and high blood pressure, suggesting new ways to diagnose and treat cardiovascular issues in lupus patients.

Contribution

The study identifies anti-endothelin receptor autoantibodies as novel biomarkers and potential therapeutic targets in lupus-related cardiovascular complications.

Findings

SLE patients have significantly elevated anti-ETAR and anti-ETBR autoantibodies compared to controls.

Anti-ETAR autoantibodies correlate with higher blood pressure and markers of endothelial activation.

These autoantibodies are elevated in SLE patients regardless of hypertension status.

Abstract

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 (ETAR) and endothelin receptor B (ETBR) 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-ETAR autoantibodies, anti-ETBR autoantibodies, and sVCAM-1 in individuals with SLE compared to controls. Anti-ETAR autoantibodies, Anti-ETBR autoantibodies, and sVCAM-1 levels were significantly increased in SLE subjects independent of HTN status. Anti-ETAR autoantibodies correlated positively with systolic and diastolic blood pressure, sVCAM-1, sICAM-1, and anti-ETBR 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.

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