Rheumatoid Arthritis: Mannarino E

Sherer Y, Gerli R, Gilburd B, Bartoloni Bocci E, Vaudo G, Mannarino E, Shoenfeld Y. · Department of Medicine B and Center of Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel. · Lupus. · Pubmed #17439932 No free full text.

Abstract: Antiphospholipid and anti-oxidized LDL (anti-oxLDL) antibodies are associated with thrombosis and atherosclerosis. Rheumatoid arthritis (RA) is characterized by excess atherosclerosis and cardiovascular diseases. Our aim was to determine whether antiphospholipid and anti-oxLDL antibodies are associated with early atherosclerotic changes in RA. The levels of IgG and IgM anticardiolipin, IgG and IgM anti-beta-2-glycoprotein-I and anti-oxLDL autoantibodies have been evaluated in 82 patients having RA. Carotid artery intima-media thickness (IMT) was measured in the carotid arteries in the common carotid, bifurcation and internal carotid arteries. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 7 with medium-to-high levels considered being clinically relevant. These patients had significantly elevated mean carotid and carotid bifurcation IMT compared with RA patients without elevated anticardiolipin. No such association was found regarding other autoantibodies tested. Anticardiolipin antibodies are prevalent in RA and are associated with early atherosclerotic changes, supporting a rational for measuring them in RA, and upon detection treat the patients in order to decrease chances of atherosclerosis progression and thrombosis.

Vaudo G, Bocci EB, Shoenfeld Y, Schillaci G, Wu R, Del Papa N, Vitali C, Delle Monache F, Marchesi S, Mannarino E, Gerli R. · University of Perugia, Perugia, Italy. · Arthritis Rheum. · Pubmed #16320337 links to  free full text

Abstract: OBJECTIVE: Systemic lupus erythematosus and rheumatoid arthritis represent independent risk factors for atherosclerosis (ATS), although this may be confounded by continuous pharmacologic treatment. Primary Sjögren's syndrome (SS) shares several features of these diseases and may therefore represent an interesting model for verifying the presence of accelerated ATS in the absence of pharmacologic interference. The present study therefore used this model to describe the presence of accelerated ATS in a group of young women. METHODS: Thirty-seven untreated white women with primary SS were evaluated clinically and serologically. Carotid and femoral artery intima-media thickness (IMT) was evaluated in the patients and in 35 age-matched healthy women who served as controls. RESULTS: The patients had a higher IMT than did the controls at both the carotid (mean +/- SD 0.82 +/- 0.24 mm versus 0.63 +/- 0.20 mm; P < or = 0.001) and the femoral (0.81 +/- 0.26 mm versus 0.67 +/- 0.23 mm; P < or = 0.019) levels, and had a higher prevalence of carotid intima-media thickening (49% versus 11% of controls; P < or = 0.001). The patient subset with high carotid IMT showed an increased prevalence of leukopenia and circulating anti-SSA antibodies; interestingly, the number of leukocytes was inversely correlated with the level of arterial IMT in patients with SS. Multivariate analysis demonstrated that anti-SSA antibodies were independent predictors of carotid artery thickening, while leukopenia was a predictor of both carotid and femoral artery thickening. CONCLUSION: Subclinical ATS was evident in about one-half of the patients with SS. Its association with some features typical of connective tissue diseases, such as the presence of anti-SSA and leukopenia, suggests that the immune dysregulation characterizing this autoimmune disorder may play a key role in inducing early ATS.

Sherer Y, Gerli R, Vaudo G, Schillaci G, Gilburd B, Giordano A, Bocci EB, Allegrucci R, Marchesi S, Mannarino E, Shoenfeld Y. · Department of Medicine B and Center of Autoimmune Diseases, Sheba Medical Center, Tel Hashomer 52621, Israel. · Ann N Y Acad Sci. · Pubmed #16126971 No free full text.

Abstract: Antiphospholipid antibodies characterize the antiphospholipid syndrome (APS), but they can also be found in various autoimmune, infectious, and malignant conditions. This study's objectives were to detect the prevalence of antiphospholipid and antioxidized low-density lipoprotein (anti-oxLDL) antibodies among patients with rheumatoid arthritis (RA) who did not have clinical manifestations of APS. Using a standard enzyme-linked immunosorbent assay (ELISA), we evaluated the levels of immunoglobulin G (IgG) and IgM anticardiolipin, IgG, and IgM anti-beta-2-glycoprotein-I (anti-beta(2)GPI), and anti-oxLDL autoantibodies in 82 patients with RA. The cutoff levels for detecting these autoantibodies were 15 IgG phospholipid units (GPL), 15 IgM phospholipid units (MPL), and 25 ELISA units (EU)/mL, respectively. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 10 with low levels of IgG anticardiolipin and 7 with medium to high levels of anticardiolipin autoantibodies. IgM anticardiolipin was found in only 1 (1%) patient, and both IgG and IgM anti-beta(2)GPI were found in 3 (4%) patients with RA. Elevated levels of anti-oxLDL antibodies were found in 8 (10%) patients, 4 of whom also had elevated levels of IgG anticardiolipin. We conclude that IgG anticardiolipin autoantibodies can be found in about one-fifth of RA patients who do not have clinical manifestations of APS. Whether the presence of anticardiolipin signifies increased risk for thrombosis and atherosclerosis in these patients should be studied further.

Gerli R, Sherer Y, Vaudo G, Schillaci G, Gilburd B, Giordano A, Bocci EB, Allegrucci R, Marchesi S, Mannarino E, Shoenfeld Y. · Section of Internal Medicine and Oncological Sciences, Center for the Study of Rheumatic Diseases, University of Perugia, Perugia, Italy. · Ann N Y Acad Sci. · Pubmed #16126969 No free full text.

Abstract: This study was designed to compare intima media thickness (IMT) of the carotid arteries among rheumatoid arthritis (RA) patients and controls and to determine whether disease-associated characteristics, smoking, and other classic risk factors for atherosclerosis are associated with IMT values. IMT was measured in the carotid arteries of 101 RA patients and 75 control subjects. The IMT was evaluated in the common carotid (CC), carotid bifurcation (BI), and internal carotid (IC). Eight IMT values were calculated including four mean and four maximal values of CC, BI, IC, and carotid artery (C). The following data were obtained for every patient: age, sex, body mass index (BMI), presence of erosions, extra-articular manifestations, rheumatoid factor, medications, hypertension, hypercholesterolemia, diabetes mellitus, smoking status, daily number of cigarettes, number of smoking years, family history of cardiovascular diseases (CVD), and erythrocyte sedimentation rate (ESR) levels. RA patients had significantly higher mean-BI IMT than controls (1.02 mm vs. 0.89 mm; P < 0.01), higher incidence of increased mean-BI IMT and max-BI IMT, but lower incidence of increased max-IC IMT than controls. Factors significantly associated with IMT in the controls were age, BMI, and hypertension, whereas factors significantly associated with IMT in RA patients were age and smoking status. Mean carotid IMT was associated with all characteristics related to smoking in RA patients. Current smokers had higher mean carotid IMT and internal carotid artery IMT than former smokers. RA is associated with higher carotid artery bifurcation IMT. The profile of factors associated with IMT values is different between RA patients and controls. Smoking is an important factor augmenting early atherosclerosis in RA patients.

Bartoloni Bocci E, Marchesi S, Delle Monache F, Vaudo G, Giordano A, Ragni Alunni F, Angrisani C, Mannarino E, Shoenfeld Y, Gerli R. · Centro per lo Studio delle Malattie Reumatiche, Sez. di Medicina Interna e Scienze Oncologiche, Policlinico di Monteluce, 06122 Perugia. · Reumatismo. · Pubmed #15776142 links to  free full text

Abstract: BACKGROUND: There is an increasing body of evidence suggesting that subjects with rheumatoid arthritis (RA) are characterized by acceleration of atherosclerotic process of arterial wall. However, all investigations performed so far to evaluate subclinical atherosclerosis in RA included subjects without selection for age and degree of disease activity that may represent confounding factors in such an evaluation. OBJECTIVES: To verify signs of accelerated subclinical atherosclerosis in young subject suffering from RA but with low disease activity. METHODS: Thirty-two patients with RA and 28 age- and sex-matched control subjects with non-inflammatory rheumatic diseases were enrolled. Inclusion criteria were age less than 60 and low disease activity with score < or =3.2 according to DAS28, while subjects with traditional risk factors for and/or overt cardiovascular disease were ruled out from the study. Both patients and controls underwent evaluation of carotid and femoral artery intima-media thickness by ultrasounds. RESULTS: Patients had higher intima-media thickness than controls of all the sites evaluated at carotid artery level, whereas there were no differences at the comparison of the superficial and common femoral artery wall. At the univariate analysis, a positive correlation between LDL cholesterol levels and intima-media thickness at the carotid bifurcation was found. CONCLUSIONS: Young patients with RA and low disease activity have acceleration of atherosclerosis development as shown by increased intima-media thickness of carotid artery with respect to subjects without inflammatory rheumatic disease. It is conceivable that the organic damage of arterial wall could be the result of persistent endothelial dysfunction induced by chronic inflammation and immune dysregulation which characterize RA.

Gerli R, Schillaci G, Giordano A, Bocci EB, Bistoni O, Vaudo G, Marchesi S, Pirro M, Ragni F, Shoenfeld Y, Mannarino E. · Center for the Study of Rheumatic Diseases, Section of Internal Medicine and Oncological Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Policlinico di Monteluce, I-06122 Perugia, Italy. · Circulation. · Pubmed #15159291 links to  free full text

Abstract: BACKGROUND: Peripheral blood expansion of an unusual CD4+ T-cell subset lacking surface CD28 has been suggested to predispose rheumatoid arthritis (RA) patients to develop more aggressive disease. However, the potential association between CD4+CD28null T cells and early atherosclerotic changes in RA has never been investigated. METHODS AND RESULTS: The number of circulating CD4+CD28null cells was evaluated in 87 RA and 33 control subjects who also underwent evaluation of carotid artery intima-media thickness (IMT) and endothelial function via flow-mediated vasodilation (FMV). Patients had higher IMT and lower FMV compared with control subjects. The frequency of CD4+CD28null cells was significantly higher in patients than in control subjects. Twenty patients with persistent expansion of circulating CD4+CD28null cells had more marked increase of carotid artery IMT and stronger decrease of brachial artery FMV. Blockade of tumor necrosis factor-alpha led to a partial reappearance of the CD28 molecule on the CD4+ cell surface. CONCLUSIONS: Circulating CD4+CD28(null) lymphocytes are increased in RA. Patients with persistent CD4+CD28null cell expansion show preclinical atherosclerotic changes, including arterial endothelial dysfunction and carotid artery wall thickening, more significantly than patients without expansion. These findings suggest a contribution of this cell subset in atheroma development in RA. Moreover, the demonstration that tumor necrosis factor-alpha blockade is able to reverse, at least in part, the CD28 deficiency on the CD4+ cell surface may be of interest for possible innovative therapeutic strategies in cardiovascular diseases.

Vaudo G, Marchesi S, Gerli R, Allegrucci R, Giordano A, Siepi D, Pirro M, Shoenfeld Y, Schillaci G, Mannarino E. · Internal Medicine, Angiology and Arteriosclerosis, University of Perugia School of Medicine, Perugia, Italy. · Ann Rheum Dis. · Pubmed #14672888 links to  free full text

Abstract: BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease. Endothelial dysfunction represents the earliest stage of atherosclerosis. OBJECTIVE: To evaluate the influence of chronic inflammatory state on endothelial function in patients with RA by measuring endothelial reactivity in young patients with RA with low disease activity and without traditional cardiovascular risk factors. METHODS: Brachial flow mediated vasodilatation (FMV), assessed by non-invasive ultrasound, was evaluated in 32 young to middle aged patients with RA (age </=59 years), with DAS28 </=3.2 and without overt cardiovascular disease, and in 28 age and sex matched controls. RESULTS: Mean (SD) FMV was significantly lower in patients than in controls (3.2 (1.3)% v 5.7 (2.0)%; p<0.001), inversely related to low density lipoprotein cholesterol (r = -0.45, p<0.05) and C reactive protein (CRP), expressed as the value at the moment of ultrasound evaluation (r = -0.44, p<0.05), as the average of CRP levels evaluated at different times during the disease (r = -0.47, p<0.05), or as the average of >/=4 determinations multiplied by the disease duration (r = -0.40, p<0.05). In a multivariate regression model, a lower brachial flow mediated vasodilatation was independently predicted by low density lipoprotein cholesterol (beta = -0.40, p<0.05), average CRP levels multiplied by the disease duration (beta = -0.44, p<0.05), and brachial artery diameter (beta = -0.28, p<0.05). CONCLUSIONS: Young to middle aged patients with RA with low disease activity, free from cardiovascular risk factors and overt cardiovascular disease, have an altered endothelial reactivity that seems to be primarily related to the disease associated chronic inflammatory condition.

Marchesi S, Vaudo G, Lupattelli G, Mannarino E. · No affiliation provided · Arthritis Rheum. · Pubmed #13130499 links to  free full text

This publication has no abstract.