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G Valesini

Publications and source records attributed to G Valesini.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cardiolipin on the surface of apoptotic cells as a possible trigger for antiphospholipids antibodies.

This study provides evidence that cardiolipin (CL) molecules are expressed on the surface of apoptotic cells and are recognized by antiphospholipid antibodies, purified from patients with the antiphospholipid antibody syndrome (APS). CL expression on cell surface was demonstrated by high performance thin layer chromatography analysis of phospholipids from plasma membrane purified fractions and by the positive staining with the CL-specific dye nonyl-acridine orange. This finding was complemented with the observation that aCL IgG purified from patients with APS bind to the surface of apoptotic cells. This staining shows a clustered distribution mostly localized on surface blebs. Interestingly, CL exposure on the cell surface preceded the DNA fragmentation, as shown by cytofluorimetric analysis. These findings demonstrate that exposure of CL molecules on the cell plasma membrane is an early event of the apoptotic cellular program that may represent an in vivo trigger for the generation of aCL.

Acridine Orange↗
PubMed2000

Safety profile and causes of withdrawal due to adverse events in systemic lupus erythematosus patients treated long-term with cyclosporine A.

Several case reports and uncontrolled trials have established the use of cyclosporine A (CsA) in systemic lupus erythematosus (SLE) but some concerns have been raised because of its kidney damaging effects. We here report the results of a retrospective follow-up study designed to assess the safety profile and causes of discontinuation due to adverse events in SLE patients treated with CsA. We treated 56 SLE patients with oral CsA at doses of 3-5 mg/kg for an average of 26 months. Adverse events not leading to the discontinuation of therapy were observed in 62.5% of the patients, the most frequent being hypertrichosis. CsA was stopped because of the occurrence of side effects in 9/56 (16%) of the patients. The most common were nephrotoxicity (3/9) and the occurrence of tremors (3/9). These effects were always reversible within three months of CsA withdrawal. The patients who were older than 40 y had a significant slightly increased risk of stopping CsA therapy for any adverse events (RR 1.08; CI 95% 1.03-1.14). In comparison with previous studies, this study involved a larger cohort of SLE patients who were evaluated for a longer period of follow-up, and confirmed the good tolerability of CsA in these subjects.

Adolescent↗
PubMed2000

Treatment of thrombosis associated with immunological risk factors.

The clinical management of the antiphospholipid syndrome is aimed at assessing the thrombotic risk of an individual in order to undertake primary prevention for the asymptomatic subject positive for antiphospholipid antibodies or prophylaxis of major ischaemic events for the patient who has already experienced thrombosis. Lack of immunological parameters with a clear predictive value and the current concept that thrombosis is a multifactorial disease suggest that all the known acquired and genetic thrombotic risk factors should be taken into account in antiphospholipid syndrome. Low-dose aspirin and hydroxychloroquine have been proven useful in primary prevention. While convincing evidence has been provided that aspirin and hydroxychloroquine do not prevent secondary thrombosis, much debate has recently developed on the level of oral anticoagulation needed to guarantee this prevention. Main concerns are also related to duration of anticoagulation therapy, risk of bleeding, and the increased risk of thrombosis as a result of withdrawal of the anticoagulant. Low-molecular-weight heparin has recently emerged as a valid and safe alternative for those conditions that require transient interruption or withdrawal of anticoagulation. Although treatment of the catastrophic antiphospholipid syndrome is largely empirical, the therapeutic approach based on plasmapheresis associated with immunosupression or intravenous immunoglobulin seems to be the most promising. Most attention has recently been paid to the role of oxidative stress in the pathogenesis of antiphospholipid syndrome, as a correlation between lipid peroxidation and antiphospholipid antibodies has been demonstrated. Our studies showed that lipid peroxidation may contribute to the activation of the clotting system observed in antiphospholipid syndrome and that markers of both procoagulant state and increased lipid peroxidation can be modified by experimental antioxidant treatment.

Animals↗
PubMed1999

Ongoing prothrombotic state in patients with antiphospholipid antibodies: a role for increased lipid peroxidation.

We measured the urinary excretion of Isoprostane F2alpha-III and Isoprostane-F2alpha-VI, two markers of in vivo lipid peroxidation, and the circulating levels of the prothrombin fragment F1+2, a marker of thrombin generation, in 18 antiphospholipid antibodies-positive patients, in 18 antiphospholipid antibodies-negative patients with systemic lupus erythematosus, and in 20 healthy subjects. Furthermore, 12 patients positive for antiphospholipid antibodies were treated with (n = 7) or without (n = 5) antioxidant vitamins (vitamin E at 900 IU/d and vitamin C at 2, 000 mg/d) for 4 weeks. Compared with antiphospholipid antibodies-negative patients, antiphospholipid antibodies-positive patients had higher urinary values of Isoprostane-F2alpha-III (P =. 0001), Isoprostane-F2alpha-VI (P =.006), and plasma levels of the prothrombin fragment F1+2 (P =.0001). In antiphospholipid-positive patients, F1+2 significantly correlated with Isoprostane-F2alpha-III (Rho =.56, P =.017) and Isoprostane-F2alpha-VI (Rho =.61, P =.008). After 4 weeks of supplementation with antioxidant vitamins, we found a significant decrease in F1+2 levels (P <.005) concomitantly with a significant reduction of both Isoprostane-F2alpha-III (P =.007) and Isoprostane-F2alpha-VI (P <.005). No change of these variables was observed in patients not receiving antioxidant treatment. This study suggests that lipid peroxidation might contribute to the activation of clotting system in patients positive for antiphospholipid antibodies.

Adolescent↗
PubMed1999

Frontiers of SLE: review of the 5th International Congress of Systemic Lupus Erythematosus, Cancun, Mexico, April 20-25, 1998.

OBJECTIVE: To review the recent advances in clinical and experimental research in systemic lupus erythematosus (SLE). METHODS: Review of the 5th International Congress of SLE that took place in Cancun, Mexico, on April 20-25, 1998. RESULTS: The main topics presented at the conference are summarized. These include new findings about the genetics of SLE due to fine mapping of the patients' genes and lupus mouse models, the nucleosome as a major autoantigen in SLE, serving as an immunogen for pathogenic T helper and B cells and contributing to the development of lupus nephritis, abnormalities of apoptosis as a cause of SLE, and apoptotic mechanisms as a cause of autoimmunization. Other topics included the pathophysiologic role of anti-endothelial cell antibodies in lupus with central nervous system involvement, vasculitis, the thrombotic diathesis associated with the antiphospholipid syndrome, induction of endothelial cell apoptosis and its regulation by the idiotypic network, the penetration of antinuclear antibodies to the cytoplasm and nucleus and the subsequent interaction with cellular organelles, and new aspects in the antiphospholipid syndrome, including animal models of the disease and the importance of antibodies to beta-2-glycoprotein-I and prothrombin. Advances in the clinical aspects of SLE included clinical manifestations, diagnosis, pregnancy and neonatal SLE, infections, hormones, and treatment. Additionally, four "Lectures of A Lifetime," entitled (1) What causes lupus? (2) From natural autoimmunity to autoimmune disease; (3) The idiotypic network and SLE; and (4) Late-stage morbidity and mortality in SLE-the role of accelerated atherosclerosis were presented. CONCLUSIONS: Recent advances provide new insights into the pathogenesis of SLE, as well as hope for novel therapeutic modalities and diagnostic measures. These offer the possibility of improving life quality and decreasing mortality from the disease and its complications.

Animals↗
PubMed1999

Beta2-glycoprotein I (beta2-GPI) mRNA is expressed by several cell types involved in anti-phospholipid syndrome-related tissue damage.

We report here the expression of beta2-GPI mRNA by cell types involved in the pathophysiology of the anti-phospholipid syndrome (APS), i.e. endothelial cells as a target of autoantibodies in the APS, astrocytes and neurones involved in APS of the central nervous system (CNS). Lymphocytes were also included in the study, as it has been demonstrated that patients with systemic lupus erythematosus-associated CNS diseases have serum anti-lymphocyte antibodies cross-reacting with brain antigens, and intrathecally synthesized anti-neurone antibodies. Reverse transcriptase-polymerase chain reaction followed by restriction enzyme digestion of the product obtained demonstrated the presence of beta2-GPI mRNA in all cell types here tested, cultured both in presence and absence of fetal calf serum. In both culture conditions, the same cell types were immunoreactive to an anti-beta2-GPI MoAb, as determined by indirect immunofluorescence technique. Taken together, these results indicate a direct cell synthesis of beta2-GPI, suggesting an antigenic function of beta2-GPI in the APS, including the CNS disease that occurs in this syndrome.

Actins↗
PubMed1999

Idiopathic chronic fatigue and chronic fatigue syndrome: a comparison of two case-definitions.

The aim of the study was to compare the signs and symptoms of individuals meeting two different definitions of chronic fatigue syndrome (CFS). Ninety-four patients fitting the eligibility criteria for idiopathic fatigue were enrolled into the study. Of the 94 patients, 48 met the 1988 definition of CFS, 20 the 1994 (but not the 1988) definition of CFS, and 26 met neither definition. The 1994 defined cases were more likely than 1988 defined cases, and non-syndromal individuals to be male, married, and high school educated. The 1994 cases were less likely than 1988 cases to present acute onset, self reported sore throat, mild fever lymphadenopathy, pharyngitis. In conclusion, the 1994 criteria increased the number of patients classified as CFS; however, those who fit only the 1994 criteria were less likely to have an acute symptomatic onset and signs and symptoms suggestive of an infectious process.

Adolescent↗
PubMed1998

Anti-beta 2-glycoprotein I antibodies bind to central nervous system.

Anti-beta 2-GPI antibodies (a beta 2-GPI) were found in serum from patients with anti-phospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE). Since a beta 2-GPI are often found in patients with anti-cardiolipin antibodies (aCL), their role in thrombosis as well as other central nervous system (CNS) manifestations in APS is unclear. We, therefore, investigated whether affinity-purified a beta 2-GPI bind the CNS. Astrocyte and neuron cell lines and histological sections were used as CNS substrates. Indirect immunofluorescence and/or streptavidin-biotin-peroxidase techniques revealed that astrocytes, neurons and vascular endothelium were bound by purified a beta 2-GPI (mouse monoclonal, rabbit polyclonal, human serum Ig a beta 2-GPI). This suggests a potential role for a beta 2-GPI in the CNS damage, as a beta 2-GPI might contribute to CNS pathology by either a direct interaction with astrocytes and neurons or an interaction with cerebral vascular endothelial cells. CNS immunoreaction was also demonstrated using six a beta 2-GPI-positive sera from patients (four with neurological manifestations). No binding to CNS was seen using a beta 2-GPI-negative sera, i.e. five from SLE patients (two with CNS involvement) and six healthy donors, or a monoclonal aCL without a beta 2-GPI immunoreactivity. Thus, the CNS reactivity by the a beta 2-GPI-positive sera appears specifically due to a beta 2-GPI and independent from aCL. Because of the presence of aCL in all patient sera, and the CNS involvement in three control patients, it is not possible to attribute a direct role for a beta 2-GPI in neurological diseases in this study.

Animals↗
PubMed1998

Serum anti-beta2-glycoprotein I antibodies from patients with antiphospholipid antibody syndrome bind central nervous system cells.

Sera from 20 patients with antiphospholipid syndrome (APS), primary or secondary to systemic lupus erythematosus (SLE), or with SLE, were assayed by immunoblot analysis for anti-beta2-glycoprotein I antibodies (abeta2-GPI), and by indirect immunofluorescence (IIF) technique for reactivity with astrocyte and neuron cell lines and with histological sections of human brain biopsies and monkey cerebellum. Six sera from healthy donors were studied as a control. Eleven out of the 20 patient sera contained abeta2-GPI and were immunoreactive with astrocytes and neurons, both in culture and in the histological sections, and with the endotheliocytes of the microvessels present in the histological sections. Cell localization and the pattern of immune reaction were similar to those obtained with a monoclonal antibody abeta2-GPI. Eight of the remaining patient sera, found abeta2-GPI-, did not react with the nervous substrates (and the control sera), while one exhibited immunoreactivity analogous to the abeta2-GPI+ sera. The interference of anticardiolipin antibodies (aCL) in the immunoreactivity with the nervous substrates was excluded since aCL were present in all patient sera and no immune reaction was observed in the histological sections incubated with a monoclonal aCL. Therefore, the binding of abeta2-GPI from patients to cells of the central nervous system (CNS) occurs independently from aCL. This issue may be relevant to further evaluate the potential pathogenetic role of abeta2-GPI in the CNS damage of APS-like conditions.

Animals↗
PubMed1998

Determination of antibodies to extractable nuclear antigens by commercial kits: a multicenter study.

Several enzyme immunoassays for serum antibodies to extractable nuclear antigen have recently become available. The aim of this study was to evaluate the results obtained with: (1) the same kit under different conditions; (2) different enzyme immunoassays; (3) Western blot and enzyme immunoassays. Twenty-five sera from patients with autoimmune disorders were tested in five different laboratories by one Western blot and four enzyme immunoassay commercial kits. The different methods produced comparable qualitative results. However, semiquantitative evaluation, based on a cut-off value (index), yielded different results due both to laboratory conditions and to the kits employed. Standardization of commercial products and methods should be improved so that the results of different laboratories can be compared and large-scale and follow-up studies conducted. Western blot analysis could also be useful to analyze complex reactivities, although greater experience is necessary to interpret these results correctly.

Antibodies, Antinuclear↗
PubMed1997

Enhanced lipid peroxidation in patients positive for antiphospholipid antibodies.

The mechanism leading to the formation of antiphospholipid antibodies (aPL) is still unknown. Because an in vitro study suggested that aPL may derive from pro-oxidant conditions, we sought a relationship between aPL and isoprostanes, indices of lipid peroxidation in vivo. Thirty patients with systemic lupus erythematosus have been studied. Seventeen (56.6%) were positive for aPL because they had lupus anticoagulant and/or high titer of anticardiolipin antibodies (aCL). Plasma levels of tumor necrosis factor (TNF ) and urinary excretion of two isoprostanes, 8-epi-PGF2alpha and IPF2alpha -I, free radical catalyzed oxidation products of arachidonic acid, were measured. Patients with systemic lupus erythematosus had higher urinary excretion of 8-epi-PGF2alpha and IPF2alpha -I than controls; urinary excretion of the two isoprostanes was highly correlated (Rho = 0.74, P < .0001). Urinary 8-epi-PGF2alpha was highly correlated with both aCL titer (Rho = 0. 70, P < .0001) and TNF (Rho = 0.84, P < .0001), a measure of disease severity. Excretion of this isoprostane was also higher in those patients who exhibited aPL (P < .0001). Comparable correlations were observed with the isoprostane IPF2alpha -I. No difference of 8-epi-PGF2alpha was observed between patients with and without previous history of thrombosis. This study, showing the existence of a close association between aPL and increased in vivo lipid peroxidation, supports the hypothesis that these antibodies may result from pro-oxidative conditions and suggests that inflammation may play an important role.

Adolescent↗
PubMed1997

Coexistence of anti-phospholipid antibodies and endothelial perturbation in systemic lupus erythematosus patients with ongoing prothrombotic state.

BACKGROUND: Anti-phospholipid antibodies (aPLs) were associated with an ongoing prothrombotic state in patients with systemic lupus erythematosus (SLE). Because aPLs are able to shift endothelial function toward procoagulant activity in vitro, we investigated the relationship among aPLs, ongoing prothrombotic state, and endothelial perturbation in SLE patients. METHODS AND RESULTS: We measured aPLs, anti-EC antibodies, circulating levels of prothrombin fragment F1 + 2 (F1 + 2), tumor necrosis factor-alpha (TNF-alpha), tissue-type plasminogen activator (TPA), and von Willebrand factor (vWF) in 43 SLE patients and 25 healthy subjects. Patients positive for aPLs (n = 23) had a higher prevalence of anti-EC antibodies (P = .02) and higher levels of F1 + 2 (P = .003) than aPL(-) patients. Endothelial perturbation, defined by elevated plasma levels of both TPA and vWF, was significantly associated with aPL positivity (P = .001). F1 + 2 > 1 nmol/L (mean +/- 2 SD of controls) was detected in all but one patient in whom aPL positivity and endothelial perturbation coexisted and in no aPL(+) patient without endothelial perturbation (P = .0039). F1 + 2 was significantly correlated with vWF (rho = .6, P = .004) and TPA (114 = .70, P = .0006) only in aPL(+) patients. Endothelial perturbation was closely associated with high values of TNF-alpha (P = .0001), anti-phospholipid (P = .001), and anti-EC antibodies (P = .012). In 31 patients without a clinical history of thrombosis followed up for 3 years, aPL(+) patients with endothelial perturbation showed higher F1 + 2 and TNF-alpha values than aPL(+) patients without endothelial dysfunction. CONCLUSIONS: This study shows that in SLE patients, aPL positivity is associated with an ongoing prothrombotic state only in the presence of endothelial perturbation. Our findings also suggest that aPLs and TNF-alpha might cooperate in inducing endothelial perturbation.

Adult↗
PubMed1997

No increase of serum autoantibodies during therapy with recombinant human interferon-beta1a in relapsing-remitting multiple sclerosis.

OBJECTIVES: The present investigation was aimed at establishing whether interferon (IFN)-beta would induce the synthesis of autoantibodies in patients affected by multiple sclerosis (MS). MATERIALS AND METHODS: The titres of different autoantibodies were measured in a group of 68 relapsing-remitting MS patients before and during treatment with human recombinant IFN-beta1a (3 MIU or 9 MIU subcutaneously 3x a week). ANA, anti-thyroid, anticardiolipin serum autoantibodies were assayed in all cases: when patients were found positive to ANA > 1 : 40, they were also tested for anti-DNA and anti-ENA antibodies. RESULTS: No increase was found in autoantibodies synthesis during 6 months of r-hIFNbeta1a therapy, either at low or high dosages. The percentage of patients positive to different types of autoantibodies varied between 0 and 29%, which are values similar to those already reported in untreated MS patients. CONCLUSION: Our data indicate that the short-term use of IFN-beta1a in MS is safe in terms of the induction of humoral autoimmune responses: however, further follow-up is needed to confirm these findings during long-term treatments.

Adjuvants, Immunologic↗