Association of Anti-Modified Citrullinated Vimentin with Subclinical Atherosclerosis in Early Rheumatoid Arthritis Compared with Anti-Cyclic Citrullinated Peptide

El-Barbary, Amal Mohamad; Kassem, Elham M.; Elsergany, Mervat; Essa, Salwa A-M.; Eltomey, Mohamed Adel

doi:10.3899/jrheum.101143

Cited by 43 publications

(32 citation statements)

References 39 publications

(37 reference statements)

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“…These results are in agreement with a study, indicating that anti-CCP-positive RA patients had higher CIMT than patients without evidence of these antibodies. 47 Moreover, it has been shown that citrullinated proteins are prevalent within atherosclerotic plaques, and certain anti-CCP antibodies are correlated with the CIMT 48 and associated with the atherosclerotic burden. 49 In this sense, treatment of healthy leukocytes with anti-CCPs resulted in an elevation of cell activation markers in monocytes and neutrophils, an increase of TF expression, inflammation, and oxidative stress, indicating the participation of these autoantibodies in the development of atherosclerosis and CVD.…”

Section: Discussionmentioning

confidence: 99%

Anticyclic Citrullinated Protein Antibodies Are Implicated in the Development of Cardiovascular Disease in Rheumatoid Arthritis

Barbarroja

Pérez-Sánchez

Ruiz-Limón

et al. 2014

ATVB

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Objective— Previous studies have suggested a relationship between anticyclic citrullinated protein (CCP) levels and development of cardiovascular disease in rheumatoid arthritis (RA). However, a limited number of studies have demonstrated an involvement of anti-CCPs in those processes. This study was aimed to define the specific role of these auto-antibodies in the pro-oxidative, inflammatory, and proatherogenic profile observed in leukocytes from RA patients. Approach and Results— Seventy-five RA patients and 31 healthy donors were enrolled. Carotid intima media thickness was evaluated as atherosclerosis marker. Several procoagulant and inflammatory factors, leukocyte activation, and oxidative stress markers were analyzed in plasma and leukocyte subsets. Anti-CCPs were purified from plasma of RA patients, and in vitro treatment of healthy leukocytes was conducted. High titers of anti-CCPs were associated to altered expression of prothrombotic and inflammatory markers, high oxidative stress, and pathological carotid intima media thickness in RA patients. Notably, gene expression analysis showed that lymphocytes were major players in altered inflammatory profile, monocytes were responsible for the protrombotic and atherogenic status, and neutrophils mainly displayed a pro-oxidative feature. In vitro treatment with purified anti-CCPs fully recapitulated that pathogenic profile, promoting the activation of leukocytes. Conclusions— Anti-CCPs are key players in the inflammatory and proatherogenic status of RA patients. The effects are specific of the immune cell targeted, promoting overexpression of thrombotic, inflammatory, and pro-oxidative markers in monocytes; pro-oxidative status in neutrophils; and proinflammatory profile in lymphocytes. Targeting these autoantibodies would be an excellent strategy to prevent the development of cardiovascular disease in RA.

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Section: Discussionmentioning

confidence: 99%

Anticyclic Citrullinated Protein Antibodies Are Implicated in the Development of Cardiovascular Disease in Rheumatoid Arthritis

Barbarroja

Pérez-Sánchez

Ruiz-Limón

et al. 2014

ATVB

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“…In early RA, antibodies against oxidised LDL30 and anti-modified citrullinated vimentin levels67 have been demonstrated to correlate positively with subclinical atherosclerosis. However, in the 5-year prospective study already mentioned, the incidence of overt CV events did not correlate with immunological mediators such as RF, anti-citrullinated peptide antibody and antinuclear antibodies during the first years of RA 48…”

Section: Risk Factorsmentioning

confidence: 99%

How early in the course of rheumatoid arthritis does the excess cardiovascular risk appear?

et al. 2012

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Rheumatoid arthritis (RA) is a chronic inflammatory disease which is associated with an increased cardiovascular (CV) burden. Whether the risk is already present at the time of RA diagnosis remains a key area of debate. The aim of this review was to evaluate the existence of both subclinical CV changes, including endothelial dysfunction and atherosclerosis, CV risk factors, as well as CV disease manifestations such as coronary heart disease, myocardial infarction, congestive heart failure and CV death prior to RA diagnosis and during the first few years of the disease. The state of the endothelial function remains controversial in patients with newly diagnosed RA. Studies with impaired brachial artery vasodilatory responses at baseline showed a reversal of the dysfunction after 6-12 months of anti-inflammatory therapy. Morphological evidence of arterial wall atherosclerosis, measured by carotid artery intima-media thickness or the prevalence of carotid plaques, was already present during the first year following RA diagnosis. The risk of coronary heart disease and myocardial infarction is increased even prior to and, at the latest, within 1 year of the clinical onset of RA. The prevalence of hypertension was similar among patients with RA and controls. CV mortality may not increase within the first years of RA diagnosis. In conclusion, the CV risk seems to increase sooner after the RA diagnosis than previously thought. In addition to systematic CV risk assessment, patients with early RA might benefit from being targeted with stricter than conventional CV risk prevention and intervention.

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“…When all 12 studies including healthy controls were considered together [13,14,15,16,17,18,19,20,21,22,23,24], the sensitivity estimates of anti-MCV ranged from 48.4 to 89.6%, and the specificity estimates ranged from 87.2 to 100% (. Tab.…”

Section: Diagnostic Accuracies In Ra Vs Healthy Controlsmentioning

confidence: 99%

“…A previous systematic review revealed a sensitivity of 0.64-0.84 and a specificity of 0.79-0.96 for anti-MCV in the diagnosis of RA [12], but it remains unclear if the overall diagnostic values of anti-MCV antibodies are comparable to anti-CCP antibodies. Published studies on the diagnostic accuracies of anti-MCV and anti-CCP showed controversial results [13,14,15,16,17,18,19,20,21,22,23,24]. This may be due to small sample sizes, low statistical power, and/or clinical heterogeneity.…”

mentioning

confidence: 92%

Diagnostic accuracy of anti-MCV and anti-CCP antibodies in rheumatoid arthritis

2015

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Association of Anti-Modified Citrullinated Vimentin with Subclinical Atherosclerosis in Early Rheumatoid Arthritis Compared with Anti-Cyclic Citrullinated Peptide

Abstract: Anti-MCV was as sensitive as anti-CCP3 in diagnosing early RA. Anti-MCV testing appears to be useful for monitoring associated subclinical atherosclerosis in early RA.

Cited by 43 publications

References 39 publications

Anticyclic Citrullinated Protein Antibodies Are Implicated in the Development of Cardiovascular Disease in Rheumatoid Arthritis

Anticyclic Citrullinated Protein Antibodies Are Implicated in the Development of Cardiovascular Disease in Rheumatoid Arthritis

How early in the course of rheumatoid arthritis does the excess cardiovascular risk appear?

Diagnostic accuracy of anti-MCV and anti-CCP antibodies in rheumatoid arthritis

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