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.
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The effect on lung function and respiratory symptoms of reducing of consumption of conventional cigarettes by switching to electronic cigarettes is investigated by the Cibella et al. in their Clinical Science research article on pages 1929-1937 (volume 130, issue 21).
Research Article|
September 22 2016
Antibodies to paraoxonase 1 are associated with oxidant status and endothelial activation in rheumatoid arthritis
Javier Rodríguez-Carrio;
Javier Rodríguez-Carrio
*Area of Immunology, Department of Functional Biology, University of Oviedo, 33006 Asturias, Spain
†Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Asturias, Spain
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Mercedes Alperi-López;
Mercedes Alperi-López
‡Department of Rheumatology, Hospital Universitario Central de Asturias, 33011 Asturias, Spain
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Raquel López-Mejías;
Raquel López-Mejías
§Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, 39011 Santander, Spain
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Patricia López;
Patricia López
*Area of Immunology, Department of Functional Biology, University of Oviedo, 33006 Asturias, Spain
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Francisco J. Ballina-García;
Francisco J. Ballina-García
‡Department of Rheumatology, Hospital Universitario Central de Asturias, 33011 Asturias, Spain
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Francisco Abal;
Francisco Abal
║Centro de Salud Sariego, Servicio de Salud del Principado de Asturias, 33518 Asturias, Spain
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Miguel Á. González-Gay;
Miguel Á. González-Gay
§Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, 39011 Santander, Spain
¶Department of Medicine, University of Cantabria, 39011 Santander, Spain
**Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 2193 Johannesburg, South Africa
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Ana Suárez
*Area of Immunology, Department of Functional Biology, University of Oviedo, 33006 Asturias, Spain
Correspondence: Dr Ana Suárez (email [email protected]).
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Publisher: Portland Press Ltd
Received:
May 27 2016
Revision Received:
June 28 2016
Accepted:
August 12 2016
Accepted Manuscript online:
August 12 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (21): 1889–1899.
Article history
Received:
May 27 2016
Revision Received:
June 28 2016
Accepted:
August 12 2016
Accepted Manuscript online:
August 12 2016
Citation
Javier Rodríguez-Carrio, Mercedes Alperi-López, Raquel López-Mejías, Patricia López, Francisco J. Ballina-García, Francisco Abal, Miguel Á. González-Gay, Ana Suárez; Antibodies to paraoxonase 1 are associated with oxidant status and endothelial activation in rheumatoid arthritis. Clin Sci (Lond) 1 November 2016; 130 (21): 1889–1899. doi: https://doi.org/10.1042/CS20160374
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