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Biomedical subjects

S Bombardieri

Publications and source records attributed to S Bombardieri.

At least 55 records · Page 3Linked to original sources

Autoantibodies specific for alpha-enolase in systemic autoimmune disorders.

OBJECTIVE: To analyze the presence and specificity of anti-alpha-enolase antibodies in various systemic autoimmune diseases. METHODS: Sera from patients with systemic lupus erythematosus (SLE), mixed cryoglobulinemia (MC), systemic sclerosis (SSc), and rheumatoid arthritis (RA) were tested by immunoblot on partially purified a-enolase from human kidney and on beta- and gamma-enolase. The isotype of anti-enolase antibodies was determined by means of isotype-specific monoclonal antibodies. RESULTS: IgG anti-alpha-enolase antibodies were detected in 9/33 (27%) SLE sera (6/9 patients had active renal disease), in 6/19 sera from patients with MC and nephritis, in 0/15 sera from MC patients without renal involvement, in 6/20 (30%) SSc sera, in 2/35 (6%) disease controls with RA, and in 2/32 (6%) healthy controls. The antibodies were not species-specific, but in most cases were specific for the alpha isoform of enolase. The anti-enolase immune response was not isotypically restricted. In half of the patients with SLE the anti-alpha-enolase and anti-DNA antibodies constituted distinct antibody populations, while in the other half a partial overlap of the 2 antibody specificities was observed. CONCLUSION: Anti-alpha-enolase antibodies can frequently be detected in systemic autoimmune disorders. In SLE and MC they are associated with nephritis and in SSc they are associated with severe endothelial damage. Alpha-enolase is ubiquitous, but is highly expressed in the kidney and also on the membrane of several cell types including endothelial cells. Thus, anti-alpha-enolase antibodies could contribute to renal injury not only by the local formation of immune complexes, but also by direct damage to endothelial cells.

Adult↗

Polymyositis occurring during alpha-interferon treatment for malignant melanoma: a case report and review of the literature.

Polymyositis is a systemic autoimmune disorder characterised by proximal muscle weakness which most frequently involves the limbs, neck and trunk. Alpha interferon is an antiviral molecule with well-known immunomodulatory and antiproliferative effects, but its use is often associated with a variety of side effects, in particular autoimmune phenomena. We report the occurrence of polymyositis during treatment with alpha-interferon in a patient affected by malignant melanoma. Indirect evidence suggests that in this case the patient's myositis was not linked to her neoplasia, since the melanoma was confirmed to be in remission both at the time of the diagnosis of the muscle disease and again after more than one year of follow-up.

Female↗

Systemic lupus erythematosus: clinical features in patients with a disease duration of over 10 years, first evaluation.

OBJECTIVE: Most information available about the disease course of patients with systemic lupus erythematosus (SLE) is restricted to the first 5 yr after disease onset. Data about the disease course 10 yr after disease onset are rare. The aim of this multicentre study was to describe the outcome of SLE patients with a disease duration of >10 yr. METHODS: Outcome parameters were the SLE Disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measure (ECLAM), the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR), a global damage index (DI) and required treatment. In 10 different European rheumatology centres, all SLE patients who were evaluated in the last 3 months of 1994, and who had been diagnosed with SLE at least 10 yr ago, were included in the study. RESULTS: It should be stressed that our results are confined to a patient cohort, defined by a disease duration of at least 10 yr, and who are still under clinical care at the different centres in Europe. These SLE patients still showed some disease activity, related to symptoms of the skin and musculoskeletal systems, next to the presence of renal involvement. A total of 72% of the patients needed treatment with prednisolone (</=7.5 mg). The cumulative damage was overall related to clinical features of the central nervous system (14%) and renal involvement (14%), next to deforming arthritis (14%), osteoporosis (15%) and hypertension (40%). The prevalences of obesity, Cushing appearance and diabetes are highly suggestive that the ongoing treatment and that in the past might have had an impact on the total sum of end-organ damage. CONCLUSIONS: After 10 yr, a high proportion of patients in our cohort continued to show evidence of active disease, defined by the SLEDAI as well as ECLAM. The DI was related to the involvement of the central nervous system, renal involvement and the presence of hypertension.

Adult↗

A case of SLE with acute, subacute and chronic cutaneous lesions successfully treated with Dapsone.

We describe a patient with systemic lupus erythematosus (SLE) who exhibited severe cutaneous involvement characterized by the simultaneous presence of acute, subacute and discoid lesions in association with anti-S1 antibodies. After she failed to respond to chloroquine, medium to low dose steroids, steroid pulses, retinoids and cyclophosphamide, the patient was treated with Dapsone and a dramatic improvement in the cutaneous lesions was seen after only one month.

Acute Disease↗

Development of a clinical chart to compute different disease activity indices for systemic lupus erythematosus.

Between 1990 and 1995 a European Consensus Group carried out a multicenter study to reach agreement of the definition of disease activity in systemic lupus erythematosus (SLE). A new index, the European Consensus Lupus Activity Measurement (ECLAM) index, was developed. In a second phase of the study, a prospective survey aimed at validating ECLAM and 4 other scales as steady-state and transition indices for disease activity in SLE was completed. We present the results of this survey. A standardized clinical chart was developed, together with a computer program that could automatically calculate the ECLAM score, as well as the scores for some of the disease activity scales most widely used at present, i.e., the British Isles Lupus Assessment Group, Systemic Lupus Activity Measure, SLE Disease Activity Index, and the SLE Index Score (SIS). With the participation of 28 centers in 15 different European countries, data from 121 prospectively selected new lupus patients were collected. The validity of the 5 activity scales was assessed by comparing the computed scores for each patient to a gold standard, i.e., the physician's subjective judgment on disease activity measured using a semiquantitative scale. All the indices were found to be valid instruments for measuring disease activity in SLE in both the steady-state and transition phases. The results for the various indices closely correlated with one another. Thus, the computerized chart developed by the European Consensus Group offers a simple and reliable instrument to assess disease activity and could be used to monitor lupus patients both in clinical practice and in clinical trials.

Computer Simulation↗

Immune response to an epitope of the NS4 protein of hepatitis C virus in HCV-related disorders.

NS4, a nonstructural protein of HCV, is a frequent target of antibodies in infected subjects. According to recent data, the antibodies frequently recognize the sequence 1921-40 of the NS4 protein. The aim of this work was to analyze antibody reactivity with the sequence 1921-40 in different HCV-related disorders. Although this sequence is located in a relatively invariant region of viral genome, two strain-specific sequences are described. Thus, three NS4 1921-1940 peptides were synthesized: the BK shared by most viral strains, the J6 (strain 2a), and the J8 (strain 2b). The peptides were used as antigens in the solid phase for measuring serum IgG antibodies in an ELISA assay. Antibodies reactive with the 1921-40 BK peptide were detected in 64% of sera from patients with autoimmune hepatitis (AIH), 51% from chronic hepatitis C (CHC), and 22% from mixed cryoglobulinemia (MC). The frequency of positive sera in MC was significatively lower than in AIH (P < 0.0001) or CHC (P < 0.0021). Similar results were obtained with the J6 and J8 peptides. All sera that did not react with the BK peptide were negative on J6 and J8 and conversely most sera reacting with the BK peptide also bound the J6 and the J8 peptides. No correlation was found between the genotype of the infecting virus and the presence of antibodies to any of the NS4 peptides. These results indicate that many HCV-infected subjects produce antibodies to the NS4 sequence 1921-40. The immune response to this sequence is not strain specific and varies with the different disorders associated with HCV infection.

Amino Acid Sequence↗

Behçet's disease with gastrointestinal involvement associated with myelodysplasia in a patient with congenital panhypopituitarism.

Myelodysplastic syndromes (MDS) are hematologic disorders characterised by peripheral cytopenias and the hystologic features of hematologic dysplasia. Their association with autoimmune manifestations have been suggested by several authors: recently, the appearance of Behçet's disease during MDS has been reported. We describe the occurrence of MDS in a patient affected by Behçet's syndrome with gastrointestinal involvement and congenital panhypopituitarism.

Behcet Syndrome↗

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↗

Anti-ribosomal antibodies bind the Sm proteins D and B/B'.

In order to analyse the specificity of human anti-ribosomal P protein antibodies, anti-ribosomal P protein antibodies were affinity-purified from the sera of lupus patients. Their binding capacity towards recombinant SmD protein and recombinant SmB/B' protein was evaluated by immunoblot and ELISA. Epitope mapping of SmD was performed by means of synthetic peptides. Anti-ribosomal P protein antibodies bound recombinant SmD (5/10) and SmB/B' (4/10) on immunoblot; 6/10 showed binding capacity to SmD on ELISA. Inhibition experiments using ELISA confirmed the specificity of this binding. Our data indicate the cross-reactivity of spontaneously developed anti-ribosomal P protein antibodies with the B/B' and D constituents of the Sm complex. The coexistence of anti-Sm and anti-ribosomal antibodies in lupus sera may therefore be due, at least in part, to the reactivity of a single autoantibody population.

Antibody Specificity↗

Undifferentiated connective tissue diseases: the clinical and serological profiles of 91 patients followed for at least 1 year.

The objective of this work was to evaluate the clinical and serological profiles of patients with undifferentiated connective tissue diseases (UCTD) who had been followed for at least 1 year. The retrospective analysis (197495) was based on UCTD patients diagnosed on the basis of clinical manifestations suggestive of a connective tissue disease, and the presence of at least one non-organ-specific autoantibody. A total of 91 patients were evaluated. The condition of 79 remained stable during the follow up, while in 12 the UCTD evolved to systemic lupus erythematosus (SLE) within a mean period of 3 years (min. 1 year, max. 8 years, median 2 years) after the onset of the disease. At baseline none of the variables, considered alone, showed an association with the future development of SLE. Multiple regression analysis, however, suggested that the association of sicca symptoms, Raynaud's phenomenon and/or photosensitivity was inversely correlated with the development of SLE (P = 0.0012, Fisher's exact test). The most common clinical manifestations of UCTD included arthritis, arthralgias, Raynaud's phenomenon, xerostomia, xerophthalmia and leukopenia. The stable UCTD patients showed a simple autoantibody profile characterized by a single autoantibody specificity in 82% of the cases 30% with anti-Ro/SSA alone and 28% with anti-RNP alone. This profile remained stable during the follow up. Anti-RNP antibodies alone correlated with the presence of Raynaud's phenomenon and arthritis (P < 0.001 and P < 0.01, respectively), while anti-Ro/SSA antibodies alone correlated with xerostomia and xerophthalmia (P < 0.01). In conclusion, the UCTDs in most of our patients seem to represent distinct clinical entities with a limited autoimmune repertoire rather than the early phases of definite connective tissue diseases. They could therefore provide an ideal model for the study of the clinico-serological correlations in autoimmune diseases.

Adolescent↗

The diagnosis of Sjögren's syndrome: definition and validation of classification criteria for this disorder.

Classification criteria currently exist for most of the rheumatic diseases. Different criteria sets have also been proposed in the past for Sjögren's syndrome (SS), but none of these has been validated and no single one is in general use by the entire scientific community. Between 1988 and 1996 the European Study Group for the Classification Criteria for SS performed a multicenter study in which a new classification criteria set for this disease was defined and then validated. This European set of classification criteria for SS is rapidly becoming the most widely accepted procedure to classify patients with the primary and secondary variants of the syndrome.

Diagnosis, Differential↗

Predictors of renal outcome in diffuse proliferative glomerulonephritis in systemic lupus erythematosus.

The occurrence of nephritis is considered to be the most important factor influencing the prognosis in systemic lupus erythematosus (SLE). Despite the apparent histological similarity of the lesions, however, patients with diffuse proliferative glomerulonephritis (DPGN) may exhibit different outcomes. A retrospective study was carried out on 81 SLE patients with DPGN to evaluate the prognostic significance of different clinical, serological and histological variables; in particular, 95 renal biopsies were re-evaluated and the activity and chronicity indices for the patients were determined. A positive correlation was observed between the presence of chronic lesions on renal biopsy and a poor renal outcome (< 0.001). Moreover, in the repeat biopsies the patients with a poor outcome showed a higher degree of chronic lesions. Active lesions and other clinical and serological parameters did not correlate with the outcome.

Adolescent↗

Hepatitis C virus genotype analysis in patients with type II mixed cryoglobulinemia.

OBJECTIVE: To investigate the possible role of HCV variants in the pathogenesis of mixed cryoglobulinemia. SETTING: Medical service (rheumatology and hepatology units) of urban, university-affiliated teaching hospitals. DESIGN: Analysis of viral genotypes in a cohort of patients with hepatitis C virus (HCV) infection and mixed cryoglobulinemia. PATIENTS: 90 unselected HCV-positive (anti-HCV antibody-positive and HCV RNA-positive) patients consecutively recruited at routine ambulatory visits: 29 with and 61 without (control group) mixed cryoglobulinemia. MEASUREMENTS: Clinical and histologic data; HCV RNA detection in serum and peripheral blood mononuclear cells by polymerase chain reaction (PCR); HCV genotype determination by two methods based on genotype-specific primer PCR and genotype-specific probe hybridization, respectively. RESULTS: Persistent aminotransferase increases were found in 55% of patients with mixed cryoglobulinemia. Peripheral blood mononuclear cells were infected in 80% of cases. In serum samples, HCV genotype 2a/III was detected with a higher prevalence in patients with mixed cryoglobulinemia than in controls (41% compared with 15%). The overall prevalence of genotype 2a/III in mixed cryoglobulinemia increased to 52% when findings in peripheral blood mononuclear cells were also considered. Among patients with mixed cryoglobulinemia, this genotype was more frequent in those without clinical and biochemical signs of liver disease (85%) or with serum autoantibodies (75%). CONCLUSIONS: Mixed cryoglobulinemia may be related, at least in part, to the HCV genotype infecting the host.

Aged↗

The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus.

OBJECTIVE: To develop and perform an initial validation of a damage index for systemic lupus erythematosus (SLE). METHODS: A list of items considered to reflect damage in SLE was generated through a nominal group process. A consensus as to which items to be included in an index was reached, together with rules for ascertainment. Each center submitted 2 assessments, 5 years apart, on 2 patients with active and 2 with inactive disease, of whom 1 had increased damage and the other had stable disease. Analysis of variance was used to test the factors physician, time, amount of damage, and activity status. RESULTS: Nineteen physicians completed the damage index on 42 case scenarios. The analysis revealed that the damage index could identify changes in damage seen in patients with both active and inactive disease. Patients who had active disease at both time points had a higher increase in damage. There was good agreement among the physicians on the assessment of damage in these patients. CONCLUSION: This damage index for SLE records damage occurring in patients with SLE regardless of its cause. The index was demonstrated to have content, face, criterion, and discriminant validity.

Health Status Indicators↗

CD26 surface molecule involvement in T cell activation and lymphokine synthesis in rheumatoid and other inflammatory synovitis.

T cell surface expression and the functional role of CD26 antigen (Ag), a surface ectoenzyme involved in T cell activation and migration across the extracellular matrix, were analyzed in the peripheral blood (PB) and synovial fluid (SF) from patients with inflammatory arthritides. CD26 membrane expression on T cells was detected by cytofluorometry using two different monoclonal antibodies, anti-Ta1 and anti-1F7, while cell proliferation and both IL-2 and IFN-gamma production were evaluated in anti-CD3- or anti-CD2-stimulated cell cultures after Ag surface modulation with anti-1F7. The results showed that Ta1 and 1F7 Ag expression were increased on T cells from PB of patients with active, but not inactive, rheumatoid arthritis (RA). Most SF T cells from RA or other inflammatory arthritides displayed the memory marker CD45R0 and the Ta1 Ag, but lacked the 1F7 molecule. In addition, in vitro 1F7 modulation, which enhanced RA PB T cell proliferation and both IL-2 and IFN-gamma synthesis, did not synergize with anti-CD3 or anti-CD2 in inducing IL-2-dependent activation of SF T cells, but reduced IFN-gamma production. A spontaneous reappearance of 1F7 Ag on the SF T cell surface was seen after 2-5 days in culture. Phorbol myristate acetate, able to accelerate its reexpression, also restored a normal response of SF T cells to anti-1F7 comitogenic effects. These data confirm a role of the CD26 surface molecule in regulating T cell activation and lymphokine synthesis. This observation may have important implications in the regulation of T cell activity at the joint level during chronic inflammatory processes.

Adult↗