Background: chronic inflammation and (auto)immune mechanisms are thought to account for lipid abnormal profiles in Sjögren Syndrome (SS), although exact mechanisms are ill-defined. The role of humoral responses, especially against high-density lipoproteins (HDL) and its components, has emerged in recent years in several rheumatic and musculoskeletal diseases. However, no evidence is available in SS populations.

Objectives: to evaluate humoral responses against HDL particles in SS patients and their clinical relevance.

Methods: serum levels of IgG antibodies against HDL (anti-HDL) and Apolipoprotein A1 (anti-ApoA1) were measured in 44 primary SS patients (ACR-EULAR classification criteria), 103 systemic lupus erythematosus (SLE) patients (EULAR/ACR criteria) and 80 controls. Atherosclerosis occurrence and vascular stiffness were measured by Doppler-ultrasound. Metabolomic analyses, including lipoprotein content, particle numbers, size (Liposcale test), glycoproteins A (GlycA) and B (GlycB), and major lipid classes, were performed by H-NMR.

Results: SS patients presented with increased levels of very-low density lipoproteins (VLDL) (cholesterol content: p=0.011, particle number: p<0.001), intermediate low-density lipoproteins (LDL) (p=0.034) and reduced size of HDL particles (p=0.023) compared to HC. Similarly, increased levels of triglycerides (p=0.010), phospholipids (p=0.001), phosphatidylcholine (p<0.001) and lisophosphatidylcholine (p=0.033) were observed in SS.

IgG anti-HDL and anti-ApoA1 levels were increased in pSS patients compared to controls (p=0.005 and p=0.001, respectively) and were comparable to those in SLE patients (both p>0.050). Both antibodies were not correlated in pSS (r=-0.027, p=0.862) whereas a mild correlation was found in SLE (r=0.271, p=0.007). No associations with traditional CV risk factors were retrieved. IgG anti-ApoA1 were positively correlated with ESSDAI (r=0.652, p<0.001) and clinESSDAI (r=0.652, p<0.001), whereas no associations were observed with anti-HDL (r=0.297, p=0.072; and r=0.291, p=0.061, respectively).

IgG anti-HDL, but not anti-ApoA1, were correlated with unfavourable lipoprotein features, including decreased cholesterol content on HDL particles (r=-0.465, p<0.001), decreased particle number (r=-0.439, p=0.003), increased mean particle size (r=0.332, p=0.033), altered size distribution (small HDL: r=-0.537, p<0.001) and increased VLDL particles (r=0.332, p=0.028) in pSS patients. Furthermore, IgG anti-HDL levels were found to be associated with several major lipid classes (triglycerides: r=0.519, p=0.007; free cholesterol: r=0.416, p=0.013; and phosphatidylcholine: r=-0.389, p=0.041). Similarly, IgG anti-HDL levels paralleled those of inflammatory glycoproteins (GlycA: r=0.295, p=0.050; GlycB: r=0.426, p=0.004), whereas no associations were observed with anti-ApoA1 (r=-0.048, p=0.755; and r=-0.060, p=0.700, respectively).

IgG anti-HDL were unrelated to atherosclerosis plaque occurrence (p=0.728) nor with cIMT (r=0.051, p=0.754). However, the associations between anti-HDL and lipid species were dependent on the atherosclerosis status, being restricted to those with atherosclerosis plaques (n=22), whereas no associations were retrieved in the atherosclerosis-free group (n=20).

Conclusion: humoral responses against HDL particles occur in SS, although differences among specificities were noticed. Anti-HDL antibodies were associated with unfavourable lipoprotein traits and major lipid classes, depending on atherosclerosis status. Anti-HDL antibodies may be considered a missing link to understand the connection between adaptive immune responses and lipid profiles in autoimmunity.

REFERENCES: NIL.

Acknowledgements: ISCIII (grant number: PI21/00054); EULAR (voucher number: Q123RSV80).

Disclosure of Interests: None declared.