PubMed Health⌕ Search

Biomedical subjects

G Valesini

Publications and source records attributed to G Valesini.

At least 19 recordsLinked to original sources
PubMed2006

Power Doppler sonography monitoring of synovial perfusion at the wrist joints in patients with rheumatoid arthritis treated with adalimumab.

OBJECTIVE: To use power Doppler sonography (PDS) to evaluate changes in synovial perfusion induced by adalimumab in the wrist joints of patients with rheumatoid arthritis. METHODS: 48 wrists of 24 patients (18 women and 6 men) were examined. Despite prior treatment with disease-modifying antirheumatic drugs, including methotrexate, patients with clinically active rheumatoid arthritis were recruited in two rheumatological centres to receive 40 mg adalimumab subcutaneously every other week. Clinical, laboratory and PDS assessments were carried out at 0, 2, 6 and 12 weeks. Clinical and laboratory measurements of disease activity included physician's global assessment of disease activity, erythrocyte sedimentation rate and serum levels of C reactive protein. The Disease Activity Score for 28 joints (DAS28) was calculated. PDS signal was scored from 0 to 3 according to the overall expression of PDS findings at the wrists. RESULTS: A significant reduction in both clinical (p<0.001) and PDS findings (p<0.001) was found at all follow-up examinations. A tendency to positive correlation (Spearman's r = 0.382; p = 0.067) was shown between reduction in PDS score and improvement in DAS28 at week 2 examination. CONCLUSION: PDS detected a rapid and significant reduction in synovial perfusion at the wrist joints of patients with rheumatoid arthritis receiving adalimumab. Ongoing follow-up will provide further information regarding the persistence of considerable reduction in PDS signal score and its correlation with DAS28.

Adalimumab↗
PubMed2006

New radiopharmaceuticals for imaging rheumatoid arthritis.

Rheumatoid arthritis (RA) is an incapacitating chronic inflammatory disease of the joints that, because of frequent relapses, requires life-long treatment. In patients affected with RA an important treatment objective is to achieve specific immune suppression in order to extinguish the immune process and arrest the disease, thus preventing or delaying complications and avoiding disease recurrence. The side effects of anti-inflammatory drugs given to improve the quality of life of these patients can be reduced with the use of specific immune therapies that block, as selectively as possible, the pathologic mechanism responsible for the disease. New therapeutic options for specific, targeted therapies for treating RA are being developed, and trials to assess the efficacy and safety of these approaches are underway. However, these therapies rely primarily on clinical assessment to evaluate treatment efficacy. It would be useful, therefore, to have an objective and reliable method that directly highlights the immune processes underlying the disease. Currently available radiopharmaceuticals for imaging RA, with a special emphasis on recently developed agents and their use in therapy decision-making and follow-up are the focus of this article.

Arthritis, Rheumatoid↗
PubMed2005

Association of CXCL13 and CCL21 expression with the progressive organization of lymphoid-like structures in Sjögren's syndrome.

OBJECTIVE: Ectopic lymphoneogenesis can occur in the salivary glands of Sjögren's syndrome (SS) patients and is associated with local antigen-driven B cell responses, autoantibody formation, and potential lymphomatous transformation. CXCL13 and CCL21 have been identified in salivary glands, but their role in ectopic lymphoneogenesis in SS remains unclear. This study aimed to evaluate the microanatomic association between CXCL13 and CCL21 expression and the acquisition of lymphoid features in periductal foci. METHODS: Salivary glands from 37 SS patients and 9 chronic sialadenitis patients were analyzed by immunohistochemistry for T cell/B cell segregation, CD21+ follicular dendritic cell networks, and peripheral lymph node addressin (PNAd)-positive high endothelial venules (HEVs) in relationship to the size of the aggregates and the expression of CXCL13 and CCL21 within infiltrating cells, epithelium, and endothelium. RESULTS: Grade 1 aggregates (10-50 lymphocytes) demonstrated predominance of nonorganized CD3+ cells, while grade 2 (>50 lymphocytes) and grade 3 (>50 with germinal centers) showed a progressive increase in CD20+ B cells and T cell/B cell segregation. This higher degree of lymphoid organization was significantly related to an increased expression of CXCL13 within infiltrating cells and PNAd+ HEV-associated CCL21-producing cells. Conversely, no association between lymphoid organization and lymphoid chemokine expression by epithelial cells was observed. CONCLUSION: The acquisition of lymphoid features by inflammatory foci in SS is critically associated with the enlargement of the inflammatory foci and with the expression of CXCL13 and CCL21 within the infiltrate, but is not associated with their expression by epithelial cells. These data strongly support an active participation of CXCL13 and CCL21 in regulating the progressive organization and maintenance of periductal foci.

Adult↗
PubMed2005

Chronic intestinal inflammation and seronegative spondyloarthropathy in children.

BACKGROUND: Spondyloarthropathy in adults has been shown to be associated with either clinical or subclinical intestinal inflammation, however this association has rarely been described in children. AIM: To report paediatric patients primarily referred to a paediatric gastroenterology centre for suspected inflammatory bowel disease and found to be affected by a seronegative spondyloarthropathy. Intestinal inflammatory lesions and rheumatological features have been described in them. SUBJECTS: During a 18-month period, 129 children were referred because of symptoms and signs suggesting an inflammatory bowel disease; 31 of them (range age: 5-17 years) were selected because they also had signs of axial and/or peripheral arthropathy and form the basis of our study. METHODS: The investigated patients underwent ileo-colonoscopy with biopsy and rheumatological assessment that also included X-ray and magnetic resonance imaging of the sacroiliac joints. RESULTS: Only seven children had a classical inflammatory bowel disease (four had ulcerative colitis, three had Crohn's disease), 12 had an indeterminate colitis, 12 a lymphoid nodular hyperplasia of the distal ileum as main feature. In the latter two groups, endoscopy and histology revealed an intestinal inflammation of chronic type distinct from the classical pattern found in inflammatory bowel disease. All were HLA B27 negative and fulfilled the European Spondyloarthropathy Study Group criteria for spondyloarthropathy (except five children classified as undifferentiated spondyloarthropathy). CONCLUSIONS: In a group of children primarily investigated for suspected inflammatory bowel disease and also presenting a seronegative spondyloarthropathy we have described both intestinal and rheumatological features. The majority of them exhibited either an indeterminate colitis or a lymphoid nodular hyperplasia of the distal ileum as main feature. These patients may be a population at risk of developing a full inflammatory bowel disease phenotype.

Adolescent↗
PubMed2005

Anti-lysobisphosphatidic acid antibodies in patients with antiphospholipid syndrome and systemic lupus erythematosus.

Lyso(bis)phosphatidic acid (LBPA) is a novel antigenic target in anti-phospholipid syndrome (APS) and antibodies directed against LBPA (aLBPA) have been detected in sera from APS patients. In this study we first evaluated aLBPA in comparison with the most widely used methods (i.e. anticardiolipin [(aCL)-enzyme-linked immunosorbent assay (ELISA)] and antibeta-2-glycoprotein-I antibodies (abeta(2)-GPI-ELISA) utilized to detect antiphospholipid antibodies in patients with primary or secondary APS, systemic lupus erythematosus, chronic HCV infection and healthy subjects. We then assessed the relationship between aLBPA, lupus anticoagulant (LAC) and the main clinical manifestations of APS. Finally, we evaluated the presence of 'pure' (i.e. beta(2)-GPI-independent) aLBPA in patients with APS and controls. The results indicate that aLBPA as well as abeta(2)-GPI display higher specificity but lower sensitivity for APS compared to aCL. Moreover, serum aLBPA correlate closely with aCL and abeta(2)-GPI in APS patients and are strictly associated with LAC positivity. We demonstrate that beta(2)-GPI binds to LBPA with affinity similar to CL, and antibodies able to react with phosholipid-protein complex exist; however, 'pure' aLBPA can also be detected in sera of APS patients. Altogether these data confirm that LBPA may be an antigenic target in APS and that aLBPA are serological markers of APS with similar sensitivity and specificity compared to abeta(2)-GPI. However, the clinical utility of aLBPA detection alone or in combination with aCL and/or abeta(2)-GPI remains to be elucidated in larger and longitudinal studies.

Adolescent↗
PubMed2005

Nailfold capillaroscopy changes in systemic lupus erythematosus: correlations with disease activity and autoantibody profile.

In systemic lupus erythematosus (SLE) nailfold capillaroscopy (NC) studies have described many different nonspecific patterns. We decided to evaluate NC changes in 44 SLE patients, comparing them with the main clinical, demographic and laboratory parameters, thus to define the real role for NC and its abnormalities in the management of this disease. Fifteen patients (34%) complained of Raynaud's phenomenon; nine of them (20%) showed relevant capillaroscopic changes (capillaroscopic score >1). In details: three patients (6.8%) had loss of capillaries, while 18 (41%) had a capillary length variability, 16 (36.5%) showing shorter and two (4.5%) longer capillaries; tortuous, meandering, bizarre, ramified and/or bushy capillaries were found in 26 (59%), seven (16%), two (4.5%), three (7%) cases, respectively. An irregular distribution of the capillary array was present in six cases (14%) while microhaemorrhages were found in four cases (9%). 4 patients (9%) showed enlarged capillaries and changes of blood flow. A capillaroscopic score >1 was more frequently associated with higher ECLAM (P < 0.005) and SLEDAI (P < 0.01) activity scores, with the presence of anti-cardiolipin (P < 0.04) and anti-Sm (P < 0.04) antibodies, and also with the presence (P < 0.04) and higher titer (P < 0.001) of anti-dsDNA antibodies. No statistically significant correlation was found among the different capillaroscopy findings, age, disease duration, or treatment, nor with any clinical manifestation of the disease, such as cutaneous, renal or neurological. Our findings confirm the importance of the microvascular involvement in SLE. The NC abnormalities seem to be related to the disease activity and to the presence of many different antibodies, highly involved in the expression of SLE. NC proved to be an easy-to-perform noninvasive technique, able to achieve useful data to better evaluate such a pleomorphic disease as SLE.

Adolescent↗
PubMed2005

[Soluble P-selectin levels in synovial fluid and serum from patients with psoriatic arthritis].

OBJECTIVE: P-selectin is an adhesion molecule expressed by activated endothelial cells and platelets favouring the leukocyte adherence to microvascular endothelium. A soluble form of this molecule has been described, whose serum levels were found to be elevated and correlate with disease activity in rheumatoid arthritis (RA) patients. Aim of this study was to determine soluble P-selectin levels in synovial fluid (SF) and serum from patients with psoriatic arthritis (PsA), where it has never been investigated, to define its involvement in PsA synovial damage. METHODS: we analysed, by ELISA, soluble P-selectin serum and SF levels in 100 patients presenting a knee joint effusion: 38 of them presented PsA, 40 RA and 22 osteoarthritis (OA). We examined the main clinical and laboratory parameters of these patients. Soluble P-selectin serum levels were also detected in 15 healthy subjects. RESULTS: soluble P-selectin SF levels were significantly higher in PsA and RA patients respect to OA subjects. Soluble P-selectin SF levels were lower than those found in serum and the SF/serum ratio was higher in PsA and RA patients respect to OA. Soluble P-selectin serum levels were not significantly different among patients and controls. No correlation was found between SF and serum levels of soluble P-selectin and the main clinical parameters. CONCLUSIONS: our study of soluble P-selectin in PsA reveals a prominent local role of this molecule, with no differences respect to RA. Histological findings may be of help in understanding the role of this adhesion molecule in PsA.

Adolescent↗
PubMed2005

[Are there differences among anti-TNFα biological drugs?].

OBJECTIVE: To provide an analysis and a guide tool in using TNFα-antagonists in the current clinical practice. METHODS: Review of the literature on the differences among the three TNFα-antagonists in terms of molecular structure, mechanism of action, pharmacokinetics, effects on the immune and neuroendocrine systems, and therapeutic indications. RESULTS AND CONCLUSIONS: Unfortunately, results of direct comparison studies are lacking. One could obviate this problem by performing statistical-mathematical extrapolations, but there are very few and very small-sized published experimental evidences.

Adalimumab↗
PubMed2005

[Effects of TNF antagonists on immune and neuroendocrine system].

In the article, the literature on the effects of TNFα-antagonists (etanercept, infliximab and adalimumab) on the immune system is reviewed. These biologic agents are employed in chronic inflammatory diseases such as rheumatoid arthritis, seronegative spondyloarthritides, as well as psoriasis and Crohn's disease. The differences of these drugs, testified by the different effects on the immune response, are discussed. These molecules exert their effect through cytokine inhibition, but they present striking differences since they can modulate macrophage activity, T cells apoptosis, leukocyte migration, and angiogenesis to a different degree. Some studies showed that these agents also affect the hypothalamo-pituitary-adrenal axis. The potential immunogenicity of these biologic agents is also discussed.

Adalimumab↗
PubMed2004

Cardiolipin and its metabolites move from mitochondria to other cellular membranes during death receptor-mediated apoptosis.

We previously reported that during death receptor-mediated apoptosis, cardiolipin (CL) relocates to the cell surface, where it reacts with autoantibodies from antiphospholipid syndrome sera. Here, we analysed the intracellular distribution of CL and its metabolites during the early phase of cell death signalling triggered by Fas stimulation in U937 cells and mouse liver. We found a redistribution of mitochondrial CL to the cell surface by using confocal microscopy and flow cytometry. Mass spectrometry revealed that CL and its metabolites relocated from mitochondria to other intracellular organelles during apoptosis, with a conversion into non-mitochondrial lipids. Concomitantly, cytosolic Bid relocated to the light membranes comprised in fraction P100, including the plasma membrane and associated vesicular systems. A direct Bid-CL interaction was demonstrated by the observation that CL and monolysoCL coimmunoprecipitated with Bid especially after Fas stimulation, suggesting a dynamic interaction of the protein with CL and its metabolites.

Apoptosis↗
PubMed2004

Screening of a HUAEC cDNA library identifies actin as a candidate autoantigen associated with carotid atherosclerosis.

The humoral immune response to endothelium has a pivotal role in the development of atherosclerosis. Using a molecular method, we sought to identify endothelial autoantigens in carotid atherosclerosis. Immunoscreening of a HUAEC expression library with IgG from a pool of two sera from patients with carotid atherosclerosis identified a clone specific to actin. We evaluated actin-specific IgG reactivity in patients with carotid atherosclerosis and compared responses with those in patients with systemic lupus erythematosus and type 1 diabetes mellitus and in healthy subjects. Enzyme-linked immunoassay detected actin-specific IgG in a significantly higher percentage of sera from patients with atherosclerosis and systemic lupus erythematosus than from healthy subjects (16/61, 26% and 13/33, 39%versus 2/41, 5%, P = 0.012 and P < 10(-4), by chi2 test). Mean optical density values were significantly higher in patients than in healthy subjects (P < 10(-4) by Student's t-test). Patients with atherosclerosis and uncomplicated plaques had significantly higher serum anti-actin IgG reactivity than those with complicated plaques (P = 0.048 by Student's t-test). Our findings suggest that actin is an autoantigenic molecule of potential clinical interest in carotid atherosclerosis.

Actins↗
PubMed2004

Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following anti-TNFalpha therapy (infliximab) in rheumatoid arthritis is associated with clinical improvement.

OBJECTIVE: To investigate the effect of infliximab treatment on anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) in patients with rheumatoid arthritis. METHODS: 43 patients with rheumatoid arthritis not responding to disease modifying anti-rheumatic drugs (DMARD) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks, and subsequently bimonthly, in combination with methotrexate. Serum samples were collected at baseline and at week 24. A commercial enzyme linked immunosorbent assay was used to test for anti-CCP antibodies; RF were detected using a quantitative nephelometric assay. RESULTS: At baseline, 38 of the 43 patients (88%) were positive for anti-CCP antibodies, and 41 (95%) were positive for RF. The serum titre of anti-CCP and RF decreased significantly after six months of treatment (p = 0.0001 and p<0.0001, respectively). When the patients were grouped on the basis of their clinical response to infliximab, a significant decrease in serum anti-CCP antibodies and RF was observed only in patients who had clinical improvement (ACR 20 and ACR 50). CONCLUSIONS: Anti-TNFalpha treatment in rheumatoid arthritis results in a decrease in the serum titres of RF and anti-CCP antibodies in patients showing clinical improvement, suggesting that these measurements may be a useful adjunct in assessing treatment efficacy.

Adult↗
PubMed2003

Polymorphism of the Duffy erythrocyte chemokine receptor in Italian patients with Behçet's disease.

This study examined the hypothesis that the polymorphism of Duffy antigen receptor for chemokines (DARC) predisposes to and/or influences the clinical manifestations of Behçet's disease. The serum levels of IL-8 and monocyte chemotactic peptide (MCP)-1, two DARC-binding chemokines, were investigated and related to this polymorphism. Twenty-eight patients with Behçet's disease and 30 healthy blood donors were included in the study. No null phenotypes were found among the patients studied, and the frequencies of the other phenotypes (Fy((a+b-)), Fy((a+b+)), and Fy((a-b+))) did not significantly differ from those found in the blood donor group or reported in the general Caucasian population. No difference was found between the single phenotypes in terms of IL-8 and MCP-1 serum levels, and no relevant association between the clinical characteristics, Behçet's disease-associated human leukocyte antigen (HLA)-B51, and single phenotypes was observed. This investigation indicates that DARC is not a genetic trait significantly associated with or predisposing to Behçet's disease, at least in Caucasian Italians. However, the role of this polymorphism in the development and in the clinical course of the disease awaits further investigation.

Adult↗
PubMed2003

Interleukin-13 in systemic sclerosis: relationship to nailfold capillaroscopy abnormalities.

The aim of this study was to investigate whether interleukin-13 (IL-13) serum levels correlate to different nailfold capillaroscopy (NC) findings in patients with systemic sclerosis (SSc). IL-13 serum levels were measured using an ELISA method. The following NC abnormalities were considered: the presence of giant loops, haemorrhages, loss of capillaries, disorganisation of the vascular array, ramified/bushy capillaries and sludging of blood. A semiquantitative rating scale was adopted to score these changes, as well as a rating system for avascular areas and three morphological NC patterns ('early', 'active' and 'late'). Mean capillary density was determined by counting the total number of capillaries in a 1 mm length, and the arterial and venous diameters of the capillary as well as the total loop diameter were measured. In SSc patients IL-13 serum levels were significantly higher than in controls ( P < 00.1), whereas in patients with ( n=8) and without ( n=24) abnormal IL-13 serum levels (>17 pg/ml) the comparison of the NC features showed significantly relevant differences concerning a more frequent 'active' NC pattern ( P < 0.02), the presence of haemorrhages ( P < 0.0037) and sludging of blood ( P < 0.038), as well as larger total loop ( P < 0.036) and arterial ( P < 0.03) diameters, in those patients with elevated IL-13 serum levels. The study confirmed that IL-13 serum levels are higher in the sera of patients with SSc, and shows for the first time the significant correlations between this serological finding and some of the main relevant SSc capillaroscopic features, leading us to believe that this cytokine not only seems to sustain the immunological and fibrotic process of SSc, but might have a role in determining the more severe microvascular lesions in this disease.

Adult↗
PubMed2003

Relationship of interleukin-12 and interleukin-13 imbalance with class-specific rheumatoid factors and anticardiolipin antibodies in systemic lupus erythematosus.

The aim of the study was to evaluate whether the imbalance between IL-12 and IL-13 serum levels, reflecting Th1/Th2 activity, is related to class-specific circulating rheumatoid factors (RF) and anticardiolipin (aCL) antibodies in SLE. Using ELISA we measured serum IL-12, IL-13, RF and aCL antibodies in 73 SLE patients and 20 healthy controls. The determination of IL-12/IL-13 ratio showed that IL-12 levels were above (group A), equal to (group B) or below (group C) IL-13 levels in 71.2%, 15.1% and 13.7% of SLE patients, respectively. IgM-RF levels were significantly higher in group C than in groups A ( P < 0.002) and B ( P < 0.019). Group C had also higher IgM-aCL levels than group A ( P < 0.04). No relationship between IL-12/IL-13 ratio and clinical or other laboratory parameters was found. It was concluded that the increased levels of both IgM-RF and IgM-aCL in patients with prevalent Th2 activity suggest that the predominance of Th2 over Th1 could drive autoantibody production in SLE patients.

Adolescent↗
PubMed2003

Beta-2-glycoprotein I expression on monocytes is increased in anti-phospholipid antibody syndrome and correlates with tissue factor expression.

It is well known that monocytes may play an active role in thrombogenesis, since they may express on their surface tissue factor, the major initiator of the clotting cascade. The results of this investigation demonstrate beta-2-glycoprotein I (beta2-GPI) mRNA expression by human peripheral blood monocytes, indicating that these cells synthesize beta2-GPI. In addition, we show beta2-GPI expression on cell surface of these cells by flow cytometric analysis, and the presence of this protein in cell lysate by Western blot. Interestingly, beta2-GPI expression on monocytes is significantly increased in patients with anti-phospholipid syndrome (APS) or systemic lupus erythematosus (SLE) as against healthy blood donors and correlates with tissue factor expression on monocytes. These findings support the view that monocytes are able to synthesize beta2-GPI and suggest that patients with APS may have increased beta2-GPI exposure on cell surface, which leads to persistently high monocyte tissue factor expression and consequently to a prothrombotic diathesis.

Adolescent↗