Rheumatoid Arthritis: Bocci EB

Gerli R, Sherer Y, Bocci EB, Vaudo G, Moscatelli S, Shoenfeld Y. · Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. · Ann N Y Acad Sci. · Pubmed #17894000 No free full text.

Abstract: The risk of cardiovascular (CV) disease increases in patients with rheumatoid arthritis (RA). This is due to a number of different triggers including traditional and disease-related factors. Among established risk factors for CV disease, smoking may exert a more dangerous effect on arterial wall in RA than in the general population by a synergic effect with inflammatory processes of the disease. Although persistent inflammation and immune dysregulation of RA may contribute to favor other well-known CV risk factors, such as dyslipidemia, it is now clear that the disease itself represents an independent risk factor for CV disease by the action of RA chronic inflammatory process as well as humoral and cell-mediated immune mechanisms. There is evidence that CV risk is associated with severity and extension of the disease and it is of interest the fact that the presence of circulating anticyclic citrullinated peptide antibodies appears to be associated with stronger evidence of subclinical atherosclerosis in RA.

Bocci EB, Delle Monache F, Angrisani MC, Gerli R. · Sezione di Medicina Interna e Scienze Oncologiche, Centro per lo Studio delle Malattie Reumatiche, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi, Perugia. · Recenti Prog Med. · Pubmed #15844764 No free full text.

Abstract: Cardiovascular disease is the commonest cause of premature mortality in rheumatoid arthritis and several data have shown that rheumatoid arthritis is an independent risk factor for the development of atherosclerotic disease. In last years it has become evident that atherosclerosis is an immune-mediated inflammatory disorder sharing a number of pathogenic features with rheumatoid arthritis. It is conceivable, therefore, that chronically raised concentrations of proinflammatory cytokines and pathological immune response characterizing rheumatoid arthritis may play a key role in inducing acceleration of atherosclerotic processes and, consequently, in the development of cardiovascular disease in these patients.

Gerli R, Lunardi C, Bocci EB, Bobbio-Pallavicini F, Schillaci G, Caporali R, Bistoni O, Pirro M, Pitzalis C, Montecucco C. · Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. · J Rheumatol. · Pubmed #18061981 No free full text.

Abstract: OBJECTIVE: Patients with rheumatoid arthritis (RA) display high serum concentrations of soluble CD30 (sCD30), which correlate with counter-regulatory activity of CD30+ T cells in the inflamed joint. To verify the contribution of this T cell subset to disease remission, sCD30 levels were analyzed longitudinally in patients with active RA following infliximab therapy. METHODS: Infliximab plus methotrexate were started in 39 patients with active RA, while 20 patients with inactive disease, controlled by stable doses of methotrexate, acted as controls. Serial evaluations of sCD30 concentrations and disease activity indexes were performed throughout 38 weeks. RESULTS: sCD30 levels were higher in patients than in healthy controls. Rapid infliximab-induced decrease in disease activity was associated with an overall increase of sCD30 levels. In contrast, levels remained stable in controls. An inverse correlation between sCD30 levels and Disease Activity Score 28 was observed from the 22nd week of infliximab treatment. Analysis of sCD30 levels according to American College of Rheumatology response showed, after an initial general enhancement of sCD30 concentrations, a persistent increase of sCD30 in responders, but not in nonresponders. CONCLUSION: sCD30 serum levels are enhanced by tumor necrosis factor-a (TNF-a) blockade in patients with active RA and inversely correlated with disease activity, but only after some weeks of treatment. Of interest, a sustained increase of sCD30 is present only in subjects with evidence of persistent clinical response to anti-TNF-alpha. As sCD30 serum levels mirror antiinflammatory activity of joint T cells, the present data may suggest a role of synovial counter-regulatory CD30+ T cells in the induction of infliximab-mediated remission in RA.

Sherer Y, Gerli R, Bocci EB, Gilburd B, Vaudo G, Bistoni O, Shoenfeld Y. · Department of Medicine 'B' and Center of Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel. · Ann N Y Acad Sci. · Pubmed #17894004 No free full text.

Abstract: The aim of this study was to examine whether heat-shock protein (HSP)-65 autoantibodies are associated with early atherosclerosis in rheumatoid arthritis (RA). Intima-media thickness (IMT) was measured in the carotid arteries of 100 RA patients and 69 control subjects. The IMT was evaluated on both carotid arteries in the common carotid, bifurcation, and internal arteries. Every patient underwent anti-HSP-65 antibody evaluation. Anti-HSP-65 antibodies were not more prevalent among patients compared with controls. Among controls, patients having "positive" anti-HSP-65 tended to have increased carotid artery IMT compared with "negative" patients, whereas among RA patients the opposite association was noted, and positive patients had significantly decreased carotid bifurcation IMT than negative patients without elevated levels of anti-HSP-65. As opposed to the association with cardiovascular diseases and atherosclerosis of anti-HSPs in the general population, among RA patients anti-HSP-65 cannot be regarded as associated with early atherosclerosis.

Shovman O, Sherer Y, Gilbourd B, Gerli R, Bocci EB, delle Monache F, Luccioli F, Shoenfeld Y. · Department of Medicine B and Center of Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel. · Isr Med Assoc J. · Pubmed #16382698 links to  free full text

Abstract: BACKGROUND: Heat shock proteins are highly conserved immunodominant antigens found in various species. Humoral immune responses to mycobacterial HSP65 and human HSP60 have been established in a number of human autoimmune diseases. OBJECTIVE: To assess the prevalence of antibodies to HSP60 kDa and HSP65 kDa in patients with Sjögren's syndrome as compared to normal subjects. METHODS: Thirty-seven patients with SS were compared with normal controls. The antibodies against human HSP60 were measured by the Anti-Human (IgG/IgM) HSP60 ELISA kit. IgGs and IgMs to mycobacterial HSP65 were determined using an enzyme-linked immunosorbent assay with mycobacterial recombinant HSP65 antigens. RESULTS: The levels of both anti-HSP60 and -HSP65 were lower in patients compared with controls. IgG autoantibodies to HSP60 were significantly different between groups: 162 +/- 55.1 ng/ml in controls versus 112.3 +/- 30.6 ng/ml in SS patients (P < 0.001). The levels among controls of anti-HSP65 IgM isotype were also significantly higher than among the SS patients: 111.6 +/- 33.4 U/ml versus 96.1 +/- 8.9 U/ml (P= 0.01). CONCLUSIONS: The results of the present study show that the levels of different isotypes of anti- HSP60 and HSP65 antibodies were lower in patients with SS than in normal subjects. Additional studies in larger patient populations are required to evaluate the prevalence of these autoantibodies in SS patients.

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.

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.

Gilburd B, Abu-Shakra M, Shoenfeld Y, Giordano A, Bocci EB, delle Monache F, Gerli R. · Department of Medicine B, Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Hashomer, Israel. · Clin Dev Immunol. · Pubmed #15154612 links to  free full text

Abstract: BACKGROUND: Flow-based, multiplex bead arrays (MBA) have been developed for a variety of applications including the detection of antibodies to extractable nuclear antigens (ENA). It offers a rapid and sensitive method to assess multiple analyses in a single tube/well. PURPOSE: To evaluate the Athena Multi-Lyte ANA Test System utilizes Luminex Corporation's MBA technology for the detection of antinuclear antibodies (ANA) and ENA antibodies in the sera of patients with Sjogren's syndrome (SS). METHODS: MBA assay was used to detect ANA and ENA antibodies in the sera of 37 patients with SS and 96 sera from healthy subjects. RESULTS: All patients were women. Their mean age was 48.7 years and the mean disease duration was 7.27 years. ANA was found in 3 (3%) sera of healthy subjects by the AtheNA system and in 2 (2%) sera by the ELISA kit. A 99% concordance between the 2 assays was found. A 94.6% concordance between the 2 assays was found by testing the sera of patients with SS for ANA. By the AtheNA system, none of the sera of 37 patients with SS had autoantibodies reacting with Sm, Jo-1, dsDNA or histones. Anti-RNP antibody was found in 5.4% of the sera and 2.7% of the sera reacted with Scl-70 and histones. Anti-SS/A and anti-SS/B were identified in 84 and 76% of the sera, respectively. CONCLUSION: The AtheNa Multi-Lyte ANA Test System offers a sensitive and specific result for the detection of ANA and ENA antibodies in the sera of patients with SS.

Gerli R, Vaudo G, Bocci EB, Schillaci G, Bistoni O, Shoenfeld Y. · No affiliation provided · Arthritis Rheum. · Pubmed #19180496 No free full text.

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