Serum Levels of Anti-PON1 and Anti-HDL Antibodies as Potential Biomarkers of Premature Atherosclerosis in Systemic Lupus Erythematosus

Abstract

The present study aimed to evaluate the possible role of immunoglobulin G (IgG) antibodies against high-density lipoproteins (HDL) and paraoxonase 1 (PON1) as possible biomarkers of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). To this end, levels of these autoantibodies, PON1 activity and total antioxidant capacity were quantified in serum samples from 198 SLE patients, 100 healthy controls (HC) and 42 non-autoimmune individuals with traditional cardiovascular risk factors. PON1 rs662 polymorphism was analysed in a subgroup of patients and controls. Subclinical CVD were determined by Doppler ultrasound in 118 SLE patients and 30 HC, analysing carotid intima-media thickness (IMT) and blood flow parameters in internal carotid, middle cerebral and basilar arteries. Serum levels of both anti-HDL and anti-PON1 antibodies were increased in SLE patients compared with HC ( < 0.001); however, only anti-PON1 antibodies, in addition to disease activity, were significant predictors of the impaired PON1 function in SLE ( = -0.143, = 0.045). Conversely, anti-HDL antibodies were associated with higher risk of CVD (odds ratio: 3.69; = 0.012) and lower HDL levels at disease onset ( = -0.324, = 0.044). Finally, anti-PON1 antibodies were associated with carotid IMT in SLE ( = 0.201, = 0.008) and inversely related to cranial arteries blood flow velocities in patients with clinical and subclinical CVD (all < 0.001). In sum, these findings allowed us to propose serum levels of anti-PON1 and anti-HDL antibodies as potential early biomarkers of endothelial damage and premature atherosclerosis in SLE, thus constituting useful therapeutic targets for the prevention of future CVD in these patients.

Prevalence of Antiphospholipid Antibodies Negativisation in Patients with Antiphospholipid Syndrome: A Long-Term Follow-Up Multicentre Study

“…Our findings revealed no association between anti-HDL and aCL antibodies, challenging the previous notion. This is in line with previous studies from our group when analyzing other disease-related autoantibodies positivity (8)(9)(10). Recent advances have brought to light the existence of a heterogeneous group of pathogenic autoantibodies in APS.…”

“…Additionally, although differences in hyperlipidemia were observed between patients and controls, the lack of association between lipid profiles and anti-HDL levels, and the relatively small differences in lipid levels between these two groups lead us to think that this do not represent a major limitation for our findings. This point is also supported by the existing literature findings (8,(39)(40)(41)(42)(43)(44). In summary, to the best of our knowledge, this is the first study informing an association between anti-HDL antibodies and thrombotic outcomes in APS patients.…”

“…In fact, altered lipoprotein levels and/or functionality have been reported in several autoimmune conditions. In recent years, a growing body of evidence has highlighted the involvement of anti-HDL antibodies as a bridge between humoral immune-response, lipid dysfunction, oxidative status, and clinical outcomes in rheumatic disorders (8,19,20). To date, in the specific setting of APS, limited data are available regarding lipid profile and the association of anti-HDL with clinical features of the disease had been unexplored.…”

“…In addition, recent studies have discovered the existence of a heterogeneous group of autoantibodies specifically directed against lipoproteins and their components, namely IgG antihigh-density lipoproteins antibodies (anti-HDL), which have been demonstrated to impair the anti-inflammatory and antioxidative roles exerted by HDL-cholesterol (7). Higher anti-HDL levels have been described in a broad range of autoimmune diseases (8)(9)(10). However, whether anti-HDL antibodies may be associated with clinical features in APS remains unclear.…”

IgG Anti-High Density Lipoprotein Antibodies Are Elevated in Abdominal Aortic Aneurysm and Associated with Lipid Profile and Clinical Features

“…AAA patients are characterized by features of autoimmunity and lipid deposits in the wall of diseased aorta [20,21]. Emerging evidence from autoimmune diseases has revealed that the presence of autoantibodies directed against HDLc (IgG anti-HDL) may explain, at least in part, an impaired lipid profile in these conditions and they were associated with a number of disease outcomes [22][23][24][25]. Interestingly, similar results have been found in other non-autoimmune CVD conditions [26,27], hence suggesting that anti-HDL antibodies can be a common, shared mechanism across different conditions.…”