PMID- 27520507
OWN - NLM
STAT- MEDLINE
DCOM- 20170703
LR  - 20180207
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 130
IP  - 21
DP  - 2016 Nov 1
TI  - Antibodies to paraoxonase 1 are associated with oxidant status and endothelial 
      activation in rheumatoid arthritis.
PG  - 1889-99
LID - 10.1042/CS20160374 [doi]
AB  - 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-alpha  (TNFalpha) blockade. Serum PON1 activity, nitric oxide 
      (NO) and total antioxidant capacity (TAC) were measured. Interferon-gamma (IFNgamma), 
      interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1), vascular 
      endothelial growth factor (VEGF), soluble intercellular adhesion molecule (sICAM) 
      and TNFalpha 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 TNFalpha 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.
CI  - (c) 2016 The Author(s). published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Rodriguez-Carrio, Javier
AU  - Rodriguez-Carrio J
AD  - Area of Immunology, Department of Functional Biology, University of Oviedo, 33006 
      Asturias, Spain Department of Microbiology and Biochemistry of Dairy Products, 
      Instituto de Productos Lacteos de Asturias (IPLA-CSIC), 33300 Asturias, Spain.
FAU - Alperi-Lopez, Mercedes
AU  - Alperi-Lopez M
AD  - Department of Rheumatology, Hospital Universitario Central de Asturias, 33011 
      Asturias, Spain.
FAU - Lopez-Mejias, Raquel
AU  - Lopez-Mejias R
AD  - Epidemiology, Genetics and Atherosclerosis Research Group on Systemic 
      Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marques de 
      Valdecilla, IDIVAL, 39011 Santander, Spain.
FAU - Lopez, Patricia
AU  - Lopez P
AD  - Area of Immunology, Department of Functional Biology, University of Oviedo, 33006 
      Asturias, Spain.
FAU - Ballina-Garcia, Francisco J
AU  - Ballina-Garcia FJ
AD  - Department of Rheumatology, Hospital Universitario Central de Asturias, 33011 
      Asturias, Spain.
FAU - Abal, Francisco
AU  - Abal F
AD  - Centro de Salud Sariego, Servicio de Salud del Principado de Asturias, 33518 
      Asturias, Spain.
FAU - Gonzalez-Gay, Miguel A
AU  - Gonzalez-Gay MA
AD  - Epidemiology, Genetics and Atherosclerosis Research Group on Systemic 
      Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marques 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.
FAU - Suarez, Ana
AU  - Suarez A
AD  - Area of Immunology, Department of Functional Biology, University of Oviedo, 33006 
      Asturias, Spain anasua@uniovi.es.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160812
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Antibodies)
RN  - 0 (Biomarkers)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.1.8.1 (Aryldialkylphosphatase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies/*blood/immunology
MH  - Arthritis, Rheumatoid/blood/complications/*enzymology/immunology
MH  - Aryldialkylphosphatase/*immunology
MH  - Biomarkers/blood
MH  - Cardiovascular Diseases/blood/etiology/*metabolism
MH  - Cross-Sectional Studies
MH  - Female
MH  - Humans
MH  - Immunoglobulin G/blood/immunology
MH  - Interferon-gamma/blood
MH  - Male
MH  - Middle Aged
MH  - Oxidative Stress
MH  - Prospective Studies
MH  - Tumor Necrosis Factor-alpha/blood
MH  - Vascular Endothelial Growth Factor A/blood
OTO - NOTNLM
OT  - anti-paraoxonase 1 antibodies
OT  - cardiovascular disease
OT  - high-density lipoproteins
OT  - paraoxonase
OT  - rheumatoid arthritis
EDAT- 2016/08/16 06:00
MHDA- 2017/07/04 06:00
CRDT- 2016/08/14 06:00
PHST- 2016/05/27 00:00 [received]
PHST- 2016/08/12 00:00 [accepted]
PHST- 2016/08/14 06:00 [entrez]
PHST- 2016/08/16 06:00 [pubmed]
PHST- 2017/07/04 06:00 [medline]
AID - CS20160374 [pii]
AID - 10.1042/CS20160374 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2016 Nov 1;130(21):1889-99. doi: 10.1042/CS20160374. Epub 2016 
      Aug 12.