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Título: | Antibodies to paraoxonase 1 are associated with oxidant status and endothelial activation in rheumatoid arthritis |
Autor: | Rodríguez-Carrio, Javier CSIC ORCID; Alperi-López, Mercedes; López-Mejías, Raquel; López, Patricia CSIC ORCID; Ballina García, Francisco Javier; Abal, Francisco; González-Gay, M. A.; Suárez, Ana | Palabras clave: | Anti-paraoxonase 1 antibodies Cardiovascular disease High-density lipoproteins Paraoxonase Rheumatoid arthritis |
Fecha de publicación: | 22-sep-2016 | Editor: | Portland Press | Citación: | Clinical Science 130 (21): 1889-1899 (2016) | Resumen: | Traditional and non-traditional cardiovascular (CV) risk factors underlie CV disease occurrence in rheumatoid arthritis (RA). Recently, a functional impairment of high-density lipoprotein (HDL) has been observed. Although the actual players are unknown, anti-HDLs 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. 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 (CVR). A subgroup of 13 RA patients was prospectively followed upon tumour necrosis factor-α (TNFα) blockade. Serum PON1 activity, nitric oxide (NO) and total antioxidant capacity (TAC) were measured. Interferon-γ (IFNγ), interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1), vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule (sICAM) and TNFα serum levels were assessed by immunoassays. PON1 rs662 (Q > R) status was studied by reverse transcription (RT)–PCR. IgG anti-PON1 antibodies are increased in RA patients compared with 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. Anti-PON1 antibodies can be responsible for 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. | Versión del editor: | http://dx.doi.org/10.1042/CS20160374 | URI: | http://hdl.handle.net/10261/184795 | DOI: | 10.1042/CS20160374 | ISSN: | 0143-5221 | E-ISSN: | 1470-8736 |
Aparece en las colecciones: | (IPLA) Artículos |
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