Background: Traditional and non-traditional cardiovascular (CV) risk factors underlie CV disease occurrence in rheumatoid arthritis (RA). Recently, a functional impairment of HDL has been observed. Although the actual players are unknown, anti-HDL were associated with altered lipid profile, decreased paraoxonase 1 (PON1) activity and CV disease in RA. Therefore, we aimed to evaluate whether the presence of antibodies against PON1 may be involved in this scenario.
Methods: IgG anti-PON1 antibodies were quantified by ELISA in serum samples from 212 RA patients, 175 healthy controls (HC), and 54 subjects with traditional CV risk factors. A subgroup of 13 RA patients was prospectively followed upon TNFα-blockade. Serum PON1 activity, NO and total antioxidant capacity (TAC) were measured. IFNγ, IL-8, MCP-1, VEGF, sICAM and TNFα serum levels were assessed by immunoassays. PON1 rs662 (Q>R) status was studied by RT-PCR.
Results: IgG anti-PON1 antibodies are increased in RA patients compared to HC (p<0.0001) and CVR subjects (p<0.001), even after correcting for total IgG levels. Although no associations with lipid profile were found, a positive correlation with Health Assessment Questionnaire (HAQ) was observed (r=0.215, p=0.004). Anti-PON1 antibodies were associated with PON1 activity, NO and TAC, a rs662-mediated gene-dosage effect being found. Similarly, anti-PON1 antibodies were associated with sICAM serum levels in univariate and multivariate models. Finally, these antibodies were not affected by TNFα-blockade.
Conclusions: anti-PON1 antibodies can be responsible of PON1 impairment in RA patients, with a potential impact on biomarkers of oxidative status and endothelial activation. A gene-environment interaction of rs662 variants is supported.
- rheumatoid arthritis
- high-density lipoprotein
- cardiovascular disease
- ©2016 The Author(s)
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