Anti-CCP antibody in patients with established rheumatoid arthritis: Does it predict adverse cardiovascular profile?

Banerjee, Arundhati; Ghosh, Bikash Chandra; Pande, Arindam; Mandal, Shramana; Ghosh, Anirban; Palui, Rajan

doi:10.1016/j.jcdr.2012.09.003

Cited by 39 publications

(28 citation statements)

References 21 publications

(19 reference statements)

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“…26 In agreement with the existing body of literature, we found altered diverse parameters strongly associated with the development of atherosclerosis in RA patients. Thus, an increased presence of activation markers in neutrophils and monocytes and elevated expression of TF in monocytes were seen in RA patients.…”

Section: Discussionsupporting

confidence: 92%

“…24,25 In humans, there is a close relationship between anti-CCP levels and inflammation, oxidative stress, and atherosclerosis associated to RA. 26 Nevertheless, the direct effects of these auto-antibodies in the function of the human leukocytes and macrophages have not been studied yet. Here we show for the first time that anti-CCP antibodies act as direct inductors of the pro-oxidative status, inflammatory and atherogenic profile of lymphocytes, monocytes, and neutrophils in the CVD associated to RA.…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 92%

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 this setting, ACPA-positivity has been associated with the development of atherosclerosis,25–27 myocardial dysfunction28 and CV morbidity 12 29. Although underlying causal mechanisms of the association are unclear, citrullination of proteins, altering clearing function of macrophages, has been reported to occur within atherosclerotic plaque,30 and ACPA has shown an association with increased pro-thrombotic and pro-oxidative atherogenic immune cell profile 25.…”

Section: Discussionmentioning

confidence: 99%

Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts

et al. 2016

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“…These autoantibodies are associated with a higher frequency of extra-articular manifestations and poorer outcomes in RA. Atherosclerotic vascular involvement and cardiac abnormalities including lower left ventricular ejection fraction and left ventricular diastolic dysfunction were relatively higher among ACPApositive patients than in ACPA negative in patients with established RA patients [38].…”

Section: Discussionmentioning

confidence: 81%

Preserved cardiorespiratory function and NT-proBNP levels before and during exercise in patients with recent onset of rheumatoid arthritis: the clinical challenge of stratifying the patient cardiovascular risks

et al. 2015

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Rheumatoid arthritis (RA) is associated with an increased risk of myocardial infarction and congestive heart failure. In RA patients, elevated NT-proBNP levels have been reported to be a prognostic marker of left ventricular dysfunction. In this study, we evaluated cardiorespiratory functional capacity and NT-proBNP levels before and during cardiopulmonary exercise test in early RA (ERA) patients. Twenty ERA patients and 10 healthy controls were studied by color Doppler echocardiography to evaluate ventricular systolic and diastolic function. Arterial stiffness and wave reflections were quantified non-invasively using applanation tonometry of the radial artery. Cardiopulmonary treadmill test was performed to measure peak VO and VE/VCO parameters. NT-proBNP plasma levels were measured before and at the exercise peak during cardiopulmonary exercise. The peak oxygen uptake [VO (ml/min/kg)], the ventilatory equivalents for carbon dioxide (EqCO), respiratory exchange ratio and arterial stiffness were similar between patients and controls during cardiopulmonary exercise test. Basal and peak cardiopulmonary exercise NT-proBNP plasma levels were comparable in ERA patients with respect to healthy controls. When we analyzed patients according to disease characteristics and cardiovascular risk factors, ERA patients with high disease activity, BMI > 25 kg/m and ACPA positivity presented significantly higher baseline and exercise peak NT-proBNP levels. Cardiorespiratory function is preserved in patients with recent onset of rheumatoid arthritis. The increased basal and exercise peak NT-proBNP plasma levels in patients with negative disease prognostic factors represent a possible marker to stratify the cardiovascular risk in patients with early rheumatoid arthritis.

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Anti-CCP antibody in patients with established rheumatoid arthritis: Does it predict adverse cardiovascular profile?

Cited by 39 publications

References 21 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

Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts

Preserved cardiorespiratory function and NT-proBNP levels before and during exercise in patients with recent onset of rheumatoid arthritis: the clinical challenge of stratifying the patient cardiovascular risks

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