Humoral responses against high-density lipoprotein are linked to unfavourable lipid and proteomic signatures in primary Sjögren’s disease—a multi-platform approach
Rheumatology, 2026
Suárez-Díaz S., Miranda-Prieto D., López P., Alunno A., Pérez-Álvarez ?., Amigó N., Martínez-Zapico A., Suárez A., Rodríguez-Carrio J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases CVD | Pathophysiology | Serum |  Olink Target 96 |
Abstract
Objectives
Immune-mediated mechanisms and altered lipid metabolism may contribute to increased cardiovascular risk in Sjögren’s disease (SjD). Antibodies targeting high-density lipoprotein (HDL) have emerged as modulators of lipid dysfunction and inflammation in several rheumatic diseases, but their relevance in SjD remains unexplored. We aimed to characterize humoral responses against HDL in SjD and their associations with lipoprotein/lipid traits, inflammatory and proteomic features, and atherosclerosis.
Methods
IgG serum levels of antibodies against HDL (anti-HDL) and apolipoprotein A1 (anti-ApoA1) were measured in 44 SjD patients and 80 controls. Lupus patients (n = 80) were included for validation. Atherosclerosis was evaluated by Doppler-ultrasound. Lipoprotein and lipid profiling were performed by H-NMR. Cytokines and apolipoproteins were measured by immunoassays. A cardiometabolic-related protein panel was assessed by high-throughput targeted proteomics.
Results
Anti-HDL and anti-ApoA1 IgG levels were significantly elevated in SjD patients compared with controls (both P < 0.010), reaching levels comparable to those observed in lupus and independently of traditional risk factors. Anti-HDL levels were consistently associated with unfavourable lipoprotein and lipid profiles, proinflammatory cytokines and proteomic signatures linked to immune responses and tissue remodelling. In contrast, anti-ApoA1 levels were correlated with inflammation and disease activity. In SjD, the relationships between anti-HDL and lipidomic/proteomic features varied according to atherosclerosis status, although antibody levels did not differ. Anti-HDL antibodies, but not anti-ApoA1, improved risk stratification over SCORE2.
Conclusions
Humoral responses against HDL particles hallmark SjD, with different trajectories observed for functional and clinical correlates, probably linked to altered lipoprotein composition. Anti-HDL could be a missing link between autoimmunity, lipid metabolism and cardiovascular disease.