Anti-cyclic citrullinated peptide antibodies and paraoxonase-1 polymorphism in rheumatoid arthritis

El-Banna, Hassan; Jiman-Fatani, Asif A.

doi:10.1186/1471-2474-15-379

Cited by 30 publications

(33 citation statements)

References 37 publications

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“…Consistent with the relevance of PON‐1 function in HDL‐mediated cardioprotection, decreased PON‐1 activity has been related to an increased risk of cardiovascular events in the general population . Similarly, previous studies have revealed decreased PON‐1 activity in RA patients . However, the factors underlying this finding remain unclear.…”

Section: Discussionmentioning

confidence: 62%

“…Inconsistent results with regard to an association between CVD susceptibility and PON1 rs662 variants were reported in different conditions , thereby suggesting that gene–environment interactions could modulate the association between this PON1 polymorphism and CVD. Interestingly, although decreased PON‐1 activity has been found in RA patients , little is known about its relevance to CVD development.…”

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confidence: 99%

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Paraoxonase 1 Activity Is Modulated by the rs662 Polymorphism and IgG Anti–High‐Density Lipoprotein Antibodies in Patients With Rheumatoid Arthritis: Potential Implications for Cardiovascular Disease

Rodríguez‐Carrio

López‐Mejías

Alperi-López

et al. 2016

Arthritis & Rheumatology

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Objective Paraoxonase 1 (PON‐1) is a high‐density lipoprotein (HDL)–associated antioxidant enzyme that plays an important role in HDL‐mediated cardioprotection. Although genetic polymorphisms are known to modulate PON-1 activity, its involvement in cardiovascular disease (CVD) in rheumatoid arthritis (RA) is controversial, suggesting that other factors may modulate its function. Since anti‐HDL antibodies have been found to be related to an impaired lipid profile and occurrence of CVD in RA, this study was undertaken to examine the associations between PON-1 activity, anti‐HDL antibodies, and CVD according to PON1 genetic variants in patients with RA. Methods Serum PON-1 activity, using paraoxon as substrate, and IgG anti‐HDL antibodies were quantified in 212 RA patients and 110 healthy controls. The PON1 rs662 genotype (Q>R) was determined with TaqMan probes. An additional group of 13 biologics‐naive patients with RA was prospectively followed up for 3 months. Results PON‐1 activity was decreased in RA patients compared to healthy controls (P = 0.005), and an effect of the rs662 genotype was noted in both groups, with Q/Q homozygotes exhibiting the lowest PON‐1 activity. The distribution of rs662 genotypes did not differ between RA patients and healthy controls (P = 0.215). In patients carrying the Q/Q genotype, anti‐HDL antibodies were associated with impaired PON‐1 activity (P = 0.010), and levels of anti‐HDL antibodies were associated with decreased HDL levels (r = −0.680, P < 0.001) and higher prevalence of cardiovascular events, as determined in univariate and multivariate models. Furthermore, change in anti‐HDL antibody levels upon tumor necrosis factor blockade was an independent predictor of improved PON‐1 activity (β = −0.369, 95% confidence interval −0.669, −0.069; P = 0.024). Conclusion PON‐1 activity is impaired in RA in association with the rs662 genotype and anti‐HDL antibodies, the latter being recognized as a pivotal player in the link between rs662 and CVD in patients with RA.

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Section: Discussionmentioning

confidence: 62%

mentioning

confidence: 99%

Paraoxonase 1 Activity Is Modulated by the rs662 Polymorphism and IgG Anti–High‐Density Lipoprotein Antibodies in Patients With Rheumatoid Arthritis: Potential Implications for Cardiovascular Disease

Rodríguez‐Carrio

López‐Mejías

Alperi-López

et al. 2016

Arthritis & Rheumatology

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“…Serum samples collected from patients were used for the ELISA test. A positive test was considered if levels were ≥5 U/mL 2. The diagnosis of RA was made based on the American Rheumatism Association 1987 revised criteria for the diagnosis of RA 3…”

Section: Methodsmentioning

confidence: 99%

Ocular manifestations of rheumatoid arthritis and their correlation with anti-cyclic citrullinated peptide antibodies

Vignesh¹,

Srinivasan²

2015

OPTH

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PurposeTo study the ocular manifestations of rheumatoid arthritis and to correlate the role of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) with the ocular manifestations.MethodsThree-hundred and ninety-two eyes of the 196 rheumatoid arthritis patients who attended the ophthalmology outpatient department underwent a detailed ocular examination using slit lamp biomicroscopy and ophthalmoscopy. The tear function of all the patients was assessed using Schirmer’s test, tear film break-up time and ocular surface staining. The anti-CCP antibody titers for all the rheumatoid arthritis patients were estimated using enzyme-linked immunosorbent assay tests.ResultsSeventy-seven patients (135 eyes, 39%) out of the 196 patients studied had ocular manifestations typical of rheumatoid arthritis. Dry eye was the most common manifestation (28%, 54 patients). Of the patients, 78% was females (60 patients). The mean duration of rheumatoid arthritis in patients with ocular manifestations was 5.4±2.7 years and without ocular manifestations was 2.1±1.6years. Three percent of the patients had episcleritis (six patients). Scleritis was present in 2% of the patients (four patients). Peripheral ulcerative keratitis and sclerosing keratitis was present in 1% of the population each (two patients each). Eighty-five percent (66 patients) had bilateral manifestations 15% (eleven patients) had unilateral manifestations. There was a strong association between the presence of anti-CCP antibodies and ocular manifestations of rheumatoid arthritis which was shown by the statistically significant P-value of <0.0001.ConclusionOcular manifestations are a significant part of the extra-articular manifestation of rheumatoid arthritis. Dry eye was the most common ocular manifestation. There was a statistically significant association between the presence of anti-CCP antibodies specific to rheumatoid arthritis and the ocular manifestations.

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“…El-Banna et al (2014) 14 have conducted a study on rheumatoid arthritis patients that showed that there was a significant correlations between rheumatoid factor and anti CCP antibody (ACCPA) titers and decreased PON-1 activity-hence increased cardiovascular risk in those patients. This indicates a significant association between decreased antioxidant enzymes activity and the serum level of rheumatoid factor and ACCPA.…”

Section: Discussionmentioning

confidence: 99%

Serum Paraoxonase-1 Activity in Rheumatoid Arthritis Patients as a Risk Factor for Cardiovascular Comorbidity

Elshabacy

El-Rahman

El-Maghraby

et al. 2015

Egypt J of Rheumatol & Clinical Immunol

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Background: Cardiovascular disease is a leading cause of morbidity and mortality in rheumatoid arthritis (RA) patients through progressive atherosclerosis. Inflammation plays a crucial role in atherogenesis. Paraoxonase-1 (PON1) has important role in decreasing susceptibility of LDL to lipid peroxidation and prevent or at least limits the oxidation of HDL which play a role in decreasing the susceptibility to atherosclerosis. Aim of the study: To estimate serum paraoxonase-1 (PNO1), in rheumatoid arthritis patients and its correlation -if any to disease activity and lipid profile. Methods: Sixty rheumatoid arthritis patients, attending the rheumatology department at Benha teaching hospital and thirty healthy volunteers were included in this study. Both groups were subjected to full history taking, clinical examination, laboratory assessment of serum paraoxinase-1 level, lipids profile, CBC, ESR and CRP. Results: The mean serum PNO1 level in RA patients was (41.53±31.79 U/ml) and this was highly significantly lower than its level in control group (177 ± 40.77 U/ml) (p<0.001). Correlations between this level and different laboratory and clinical parameters showed significant negative correlations with ESR, CRP, DAS-28 score, cholesterol and LDL. While serum PON-1 shows significant positive correlation with HDL. ROC curve was obtained to assess for the validity of paraoxinase-1 in prediction of cardiovascular risk in severly active RA patients, it showed that paraoxinase -1 at a cut off value ≤ 26 can significantly predict cardiovascular risk in severly active RA patients, with sensitivity 76.5% and specificity 72.1%. Conclusion: low serum paraoxinase-1 activity is a real risk factor for cardiovascular disease in RA patients, as it is significantly negatively correlated with RA disease activity.

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Anti-cyclic citrullinated peptide antibodies and paraoxonase-1 polymorphism in rheumatoid arthritis

Cited by 30 publications

References 37 publications

Paraoxonase 1 Activity Is Modulated by the rs662 Polymorphism and IgG Anti–High‐Density Lipoprotein Antibodies in Patients With Rheumatoid Arthritis: Potential Implications for Cardiovascular Disease

Paraoxonase 1 Activity Is Modulated by the rs662 Polymorphism and IgG Anti–High‐Density Lipoprotein Antibodies in Patients With Rheumatoid Arthritis: Potential Implications for Cardiovascular Disease

Ocular manifestations of rheumatoid arthritis and their correlation with anti-cyclic citrullinated peptide antibodies

Serum Paraoxonase-1 Activity in Rheumatoid Arthritis Patients as a Risk Factor for Cardiovascular Comorbidity

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