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G Balestrieri

Publications and source records attributed to G Balestrieri.

101 records · Page 6Linked to original sources
PubMedDate not supplied

Relationship between anti-phospholipid and anti-endothelial cell antibodies III: beta 2 glycoprotein I mediates the antibody binding to endothelial membranes and induces the expression of adhesion molecules.

OBJECTIVE: To investigate the role of antibodies reacting with beta 2 glycoprotein I (beta 2GPI) in the antiendothelial cell binding activity present in sera from patients with the anti-phospholipid syndrome. METHODS: Sera positive for anti-phospholipid, anti-endothelial and anti-beta 2 GPI antibodies were studied for their binding activity on endothelial monolayers cultured in the presence or absence of media containing bovine serum as a source of beta 2GPI. Anti-endothelial activity was also evaluated on endothelial cells cultured without serum and supplemented with exogenous human purified beta 2GPI. Affinity purified anti-beta 2 GPI antibodies were investigated under the same experimental conditions. Finally, the effect of the incubation of these affinity purified fractions on the expression of adhesion molecules (ELAM-1) was studied. RESULTS: The reactivity of the sera decreased on endothelial cells incubated in serum-free medium, while endothelial cell binding was restored in a dose dependent manner after the addition of exogenous purified human beta 2 GPI. Affinity purified anti-beta 2 GPI antibodies obtained from the same sera retained their endothelial cell binding and were able to activate endothelial cells by inducing the ex novo surface expression of adhesion molecules (ELAM-1). CONCLUSIONS: These findings indicate that the close association between anti-endothelial and anti-phospholipid antibodies is sustained by antibodies which recognize beta 2 GPI adhering to the endothelial cells, and can promote their activation.

Antibodies, Antiphospholipid↗
PubMedDate not supplied

Induction of experimental SLE in naive mice by immunization with human polyclonal anti-DNA antibody carrying the 16/6 idiotype.

Recently, the induction of SLE in naive mice employing monoclonal anti-DNA antibodies (anti-DNA Ab) carrying the pathogenic idiotype 16/6 (16/6 Id) has been reported. In the current study we report on the induction of experimental SLE by polyclonal IgG anti-DNA Ab derived from a patient with active SLE and carrying the 16/6 Id. Two different experiments were conducted in which BALB/c mice were immunized in the footpads with 1 microgram/ml or 5 micrograms/ml of anti-DNA Ab. The first experiment showed the appearance in the immunized mice of high titre anti-DNA Ab together with antinuclear antibodies, alopecia and proteinuria. In the second experiment we compared, as immunizing agents, 16/6 positive anti-DNA Ab and 16/6 negative anti-tetanus toxoid antibodies (anti-TT Ab) obtained from the serum of the same patients. Our results show that only mice immunized with 16/6 positive antibodies produced anti-DNA Ab, while mice immunized with anti-TT Ab did not show any DNA-binding activity but, surprisingly, developed high titre anti-cardiolipin antibodies.

Alopecia↗
PubMedDate not supplied

What is the pathogenetic role of antiphospholipid antibodies?

The association between antiphospholipid antibodies (aPL) and arterial or venous thrombosis, fetal loss and thrombocytopenia defines the so-called "antiphospholipid syndrome" (APS). Despite serial studies in recent years, a clear pathogenetic mechanism(s) has not yet been demonstrated. Several authors have investigated the interaction between aPL and the membranes of blood cells (endothelial cells and platelets) involved in coagulation. aPL is also thought to affect the balance between the procoagulant and anticoagulant states by interacting with plasma or tissue cofactors. Finally, the strong association between aPL and experimental animal models of fetal loss supports a direct pathogenetic role for aPL in inducing a poor pregnancy outcome in APS women.

Abortion, Spontaneous↗
PubMedDate not supplied

International survey on the management of patients with SLE. I. General data on the participating centers and the results of a questionnaire regarding mucocutaneous involvement.

OBJECTIVE: The diagnosis and treatment of the mucocutaneous (MC), neuropsychiatric (NP), and renal (RN) manifestations of systemic lupus erythematosus (SLE) remain unsolved issues. To shed light on these issues, a questionnaire was prepared and sent to 153 lupus centres around the world, in order to determine the level of agreement between experts in their approach to these complex aspects of the disease. METHODS: The first section of the questionnaire was designed to collect information on the characteristics of the responding lupus centres. The second section was dedicated to MC manifestations, with questions focusing on: (i) the frequency of MC manifestations as a whole and of the single clinical MC entities; (ii) clinical features, outcome and therapy of subacute cutaneous lupus erythematosus (SCLE); (iii) the utility of the lupus band test (LBT); and (iv) the use of various therapeutic protocols to treat MC manifestations. RESULTS: Sixty-one questionnaires from 19 countries were analysed. Out of these, 37 were completed by Departments of Rheumatology, 21 by Departments of Internal Medicine or Clinical Immunology, and 3 by Departments of Nephrology. About 66% of these centres stated that they were currently following more than 100 lupus cases, 95% had an in-patient ward and 82% had their own laboratory. The American College of Rheumatology classification criteria and various scales for disease activity assessment were regularly used by 87% and 57% of centres respectively. The overall prevalence of MC manifestations was judged to be over 30% by 82% of the respondents (Rs), and over 60% by 36% of the Rs. Among the different MC manifestations, malar rash was reported to be the most frequent (40%), followed by alopecia (24.1%) and oral ulcers (18.6%). In reporting the prevalence of each MC manifestation, the Rs showed a low level of agreement, the coefficient of variation (CV) being > 0.75 for all of the manifestations listed with the exception of malar rash (CV = 0.54). Poor agreement among centers was also found for the reported association of various MC manifestations with SCLE (15 different answers), and on the prognostic factors for SCLE (17 different answers). There was agreement on the best procedure (up to 70% of the Rs preferred a non-UV exposed skin area) and on the utility of the LBT (83% using it only for diagnostic purpose). Hydroxychloroquine was the most popular therapeutic protocol, being used by 85% of the Rs for a wide variety of MC manifestations. Among other therapies, azathioprine was used by 59%, dapsone by 41%, and thalidomide by 35% of the Rs, all to treat a wide spectrum of MC manifestations. Pulse steroid, cyclosporin A and pulse cyclophosphamide were less commonly employed (by 27%, 22% and 13% of the Rs, respectively), and were reserved for the most severe MC manifestations, particularly vasculitis. CONCLUSION: The present survey indicates that, although most of the participating centres had extensive experience in the management of SLE, their approach to the MC manifestations was not homogeneous, and collaborative studies are clearly needed, particularly to optimise the therapeutic protocols.

Alopecia↗
PubMedDate not supplied

International survey on the management of patients with SLE. II. The results of a questionnaire regarding neuropsychiatric manifestations.

OBJECTIVE: To determine the diagnostic and therapeutic approach used in clinical practice for the management of systemic lupus erythematosus (SLE) patients with primary SLE-mediated neuropsychiatric (NP) manifestations. METHODS: A questionnaire was drawn up to assess how clinicians manage various clinical manifestations of SLE. A portion of this questionnaire was designed to assess how clinicians diagnose and treat primary NP-SLE. Most of the questions in the NP-SLE section consisted of lists of different clinical manifestations and laboratory or radiological studies that participants were asked to rate on a scale of importance [from 1 (extremely important) to 5 (not important)] to the diagnosis of primary NP-SLE. The questionnaire also assessed how different NP manifestations are treated in clinical practice. The relative importance of each clinical manifestation was determined through its mean score, and the agreement among participants on each issue was determined using the coefficient of variation (CV). Fifty-nine lupus centers participated in the NP-SLE portion of the survey. RESULTS: The clinical manifestations which were considered to be of extreme or major importance for the diagnosis of primary NP-SLE were seizures, psychosis, transverse myelitis, stroke, transient ischemic attack (TIA) and aseptic meningitis. Among the radiological and laboratory studies, only brain magnetic resonance imaging (MRI) and antiphospholipid antibodies (aPL) achieved "extremely important" mean scores (between 1 and 2). aPL testing was used routinely in the majority of patients (mean 96.8%; CV = 0.1), while brain MRI was used less frequently (mean 56.5%; CV = 0.61). Only brain MRI and cerebral angiography were considered to be helpful in differentiating cerebral vasculopathy from multi-infarct (mean score = 1.6 and 1.9, respectively), whereas a prompt response to treatment with increased doses of steroids was considered helpful in differentiating SLE-related psychosis from steroid-induced psychosis (mean score = 1.58). The results of aPL testing, coagulation tests for the lupus anticoagulant, an brain MRI were considered to be of extreme or major importance in decisions involving treatment with anticoagulant or anti-platelet therapy. Symptomatic therapies, such as heparin, or anti-convulsant, anti-platelet, oral anticoagulant, and antipsychotic therapy were the most widely used. Corticosteroids were the most frequently used immunosuppressive therapy. The administration of other immunosuppressive agents as specific treatment for NP-SLE was uncommon. CONCLUSIONS: Our survey found that in clinical practice, the NP manifestations currently considered to be diagnostic of primary SLE-mediated CNS involvement are not limited to those included in the American Rheumatism Association (ARA) criteria, e.g. seizures and psychosis. Antiphospholipid antibodies appeared to be the laboratory parameter most frequently relied upon in the diagnosis of NP-SLE, and in decisions regarding treatment. Apart from that, only brain MRI and, in selected cases, cerebral angiography seemed to be of real help in diagnosis. The lack of consensus regarding the treatment of primary NP-SLE manifestations most probably reflects both the complex nature of neurological illness in SLE patients and the lack of clear diagnostic criteria.

Adrenal Cortex Hormones↗
PubMedDate not supplied

International survey on the management of patients with SLE. III. The results of a questionnaire regarding renal involvement.

OBJECTIVE: To assess the practice patterns in the management of lupus nephritis (LN) of physicians dealing with systemic lupus erythematosus. METHODS: A multiple choice questionnaire was sent to 135 lupus centers, mainly in Europe. It was divided into 4 sections, one of which regarded LN. Sixty-one centers (40%) sent the questionnaire back before the meeting; however two of them did not fill out the LN section. Therefore, 59 valid LN questionnaires were collected and analyzed. Statistical evaluation was performed using frequency analysis and the chi-square test. RESULTS: In 50 centers (85%), renal biopsy is performed in all patients with clinically evident renal involvement, and in most of them it is repeated in cases of relapse and/or ineffectiveness of treatment. Oral steroid alone is the therapy preferred by 67% of responding physicians in patients with WHO class II LN. Multi-drug therapy is favoured by 57% in patients with class III LN, by 79% for mild-to-moderate forms of class IV LN (IVm), by 84% for moderate-to-severe forms of class IV LN (IVs), by 47% for mild-to-moderate forms of class V LN (Vm), and by 65% for moderate-to-severe forms of class V LN (Vs). Steroids plus cyclophosphamide (CYPH) is the association most commonly used for class III, IVm and IVs LN, having been indicated by 70%, 80% and 88% of the centers, respectively. Furthermore, pulse CYPH is largely preferred to oral CYPH by the majority of centers. It is worth noting that 41 centers (70%, p < 0.01) utilise the same drugs in the treatment of both WHO class IVm and IVs LN. No clear trends in the use of multi-drug associations were identifiable in the treatment of class V LN. Moreover, most of the centers (64%) said that they rely on histologic parameters in order to define renal prognosis and that they consider the chronicity index to be the best predictor of poor renal outcome (74% of the centers). CONCLUSIONS: It was possible to identify some clear trends in the behaviour of physicians who are "expert" in lupus patients: (i) they perform a renal biopsy in order to charaterize the LN and repeat it when they are faced with relapse or ineffective therapy; (ii) they treat WHO class II LN with oral steroids alone and class III and IV LN with steroids associated with CYPH (CYPH, generally in a pulse regimen); and (iii) they define renal prognosis by means of histologic predictors, especially the chronicity index. However, no trend seemed to exist for the treatment of class V LN, particularly Vm.

Biopsy↗
PubMedDate not supplied

Anticardiolipin and anti-beta 2glycoprotein I immunoassays in the diagnosis of antiphospholipid syndrome.

Autoantibodies directed to phospholipids or to phospholipid binding proteins are now studied using a growing number of laboratory tests. However, the history of the interest in this area goes back to the identification of the so-called false positive reactions in the non-treponemal serological test for syphilis (STS) and to the subsequent description of an in vitro coagulation defect called lupus anticoagulant (LAC). In the 1980s the introduction of the anticardiolipin antibody (aCL) immunoassay was a determining factor in the definition of the antiphospholipid syndrome (APS). In addition, lupus prone mice spontaneously producing aCL antibodies and normal mice passively infused with these antibodies provided useful models for the study of the pathogenic role of aPL. When in 1990 a phospholipid binding protein (beta 2glycoprotein I, beta 2GPI) was identified as the cofactor required for aCL antibody binding, the true antigenic target of the antibodies was first discussed. Soon afterwards an anti-beta 2GPI ELISA was developed that has proved to be of great clinical significance. We will discuss here the similarities and differences between these various assays (LAC, aCL, and anti-beta 2GPI), focusing on their specificity, sensitivity and practical applications.

Animals↗