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N Bizzaro

Publications and source records attributed to N Bizzaro.

At least 37 records · Page 2Linked to original sources
PubMed1999

High anti-golgi autoantibody levels: an early sign of autoimmune disease?

IgG anti-Golgi complex antibodies were detected by means of indirect immunofluorescence in the sera of five patients during routine investigation for suspected systemic autoimmune disease. The typical picture of paranuclear fluorescence was observed on the HEp-2 cell line and in tissue sections; anti-Golgi specificity was confirmed on the HEp-2 cells using the immunoperoxidase method. The phenomenon was transient in three patients with a probable viral infection and whose sera had low titre antibodies; however, it was persistent and in high concentration in the other two who, five years later, developed an autoimmune disease. Only in the sera of these last two patients were specific bands of 123, 72, 46, 37 and 26 kilodaltons found by the immunoblotting technique on cytoplasmic extracts. Although the detection of anti-Golgi autoantibodies is rare, and may represent a transitory epiphenomenon in patients with a viral infection, their presence in high titre in the absence of a clear clinical picture may constitute an early sign of systemic autoimmune disease.

Adult↗
PubMed1999

Coexistence of erythrocyte agglutination and EDTA-dependent platelet clumping in a patient with thymoma and plasmocytoma.

For 8 years, EDTA-dependent pseudothrombocytopenia was observed in a 55-year-old woman with a history of rheumatoid arthritis who had undergone surgery for lymphoepithelial thymoma 11 years earlier. The clinical picture was characterized by the presence of platelet clumps and antiplatelet antibodies of the IgM class. With the recent appearance of a solitary extramedullary plasmocytoma in the right retrobulbar region and the detection of an IgGlambda monoclonal gammopathy, blood examination also revealed erythrocyte agglutinates alongside the platelet clumps and the presence of a cold IgG antibody with antiI specificity. Both phenomena were observed in vitro when the sample temperature declined to 20 degrees C to 25 degrees C, but not at 37 degrees C. While the EDTA-dependent antiplatelet antibodies did not appear to be chronologically correlated with the patient's diseases, the cold antierythrocyte autoantibodies were strictly related to the plasmocytoma and the IgGlambda monoclonal component in serum. To our knowledge, this is the first description of an association between EDTA-dependent platelet and erythrocyte agglutinates, with a clinical picture of pseudothrombocytopenia and pseudoerythrocytopenia due to cold agglutinins.

Blood Cell Count↗
PubMed1999

[Detection of anti-ENA autoantibodies in patients with systemic connective tissue diseases. Analytical variability and diagnostic sensitivity of 4 methods].

This study was designed to assess the analytical sensitivity and rate of agreement between commercial methods and reagents, among the most used in Italy for the detection of autoantibodies to extractable nuclear antigens (ENA). Sixty-eight serum samples from patients with clinically diagnosed systemic rheumatic diseases were aliquoted and distributed to 4 hospital laboratories; three ELISA (Elias, Shield, Inova) and 1 immunoblot method (Euroimmun) were used. Overall agreement between the test reagents, for each anti-ENA specificity, was 69.1% for Ro/SSA, 83.3% for La/SSB, 70.6% for RNP, 73.5% for Sm, 91.1% for Jo1, and 82.3% for Scl70. Lack of specificity (i.e., false positive reactions) was the most important cause of low concordance. When the data were analysed according to the clinical diagnosis, total agreement and specificity improved. However, a significant difference in terms of sensitivity was observed in the SLE group (30 sera) for RNP (positivity ranged from 20% to 43%) and for Sm (from 7% to 37%), and in the Sjögren's syndrome group (13 sera) for anti-La/SSB (from 8% to 38%). Comparable data were obtained for anti-Ro/SSA (from 70% to 77%) both in the SLE and the Sjögren's syndrome group. Sensitivity of all 4 reagents was good in detecting anti-Scl70 autoantibodies in the 8 patients with diffuse systemic sclerosis, as well as anti-Jo1 autoantibody in the 5 polymyositis patients, with a 100% and a 95% agreement, respectively. These data suggest the need of a better standardization of commercial reagents and analytical procedures, and the opportunity that every laboratory should perform anti-ENA determination by at least two different methods, since none of the methods tested was completely reliable in detecting all anti-ENA autoantibody specificities.

Antibodies, Antinuclear↗
PubMed1998

Variability between methods to determine ANA, anti-dsDNA and anti-ENA autoantibodies: a collaborative study with the biomedical industry.

This study was performed by the Italian Society of Laboratory Medicine (SIMeL) in order to establish the variability between the different analytical systems currently used in clinical laboratories for the detection of autoantibodies diagnostic of systemic autoimmune disease. Sixteen industrial, and two university laboratories participated in this study which entailed the determination of anti-nuclear (ANA), anti-dsDNA and anti-ENA antibodies in 11 sera from patients with clinically diagnosed systemic rheumatic disease, using reagents produced by these companies and different methodologies (indirect immunofluorescence, immunoenzymatic assay, counterimmunolectrophoresis, immuno and western blotting). We found 93.5% agreement between the methods used for the detection of ANA, 85.2% for anti-dsDNA antibodies, and 86.9% for anti-ENA antibodies. Among the anti-ENA antibodies, regardless of the method used, detection percentages were excellent for anti-RNP and anti-SSB/La (100%), good for anti-SSA/Ro (93%), but unacceptable for the anti-Jo-1 (67%), anti-Scl70 and anti-Sm (47%) antibodies. This further stresses the need for rigorous standardisation of commercial reagents and analytical procedures, as well as the introduction of external quality assessment (EQA) programs, and a complete definition of operative protocols adjusted to the sensitivity and specificity of the various methods.

Antibodies, Antinuclear↗
PubMed1998

Two novel mutations (Pro864His, Val867Glu) causing type 2A von Willebrand disease and affecting a single restriction site in exon 28.

We detected two transversions in two unrelated Italian patients with type 2A von Willebrand disease (VWD): a C to A at nucleotide 8821 and a T to A at nucleotide 8830, resulting in the missense mutations Pro864His and Val867Glu respectively. Both mutations were in the heterozygous form and abolished the BstXI restriction site in exon 28 of the VWF gene. In both mutations plasma VWF multimer pattern improved by antiproteases. Moreover, DDAVP normalized plasma VWF multimers in the Pro864His patient, especially when protease inhibitors were present. These new mutations appear to be of the 2A VWD subtype due to the increased susceptibility to proteases.

Adult↗
PubMed1998

IgG platelet antibodies in EDTA-dependent pseudothrombocytopenia bind to platelet membrane glycoprotein IIb.

EDTA-dependent pseudothrombocytopenia (PTCP) consists of an inappropriate low platelet count caused by autoantibodies present in the serum samples reacting with platelets only in EDTA-anticoagulated blood. By using immunoprecipitation and Western blot techniques, we studied the immunochemical specificity of platelet agglutinating autoantibodies in the serum samples of 10 patients with PTCP. Furthermore, to evaluate a possible role of PTCP-associated IgG autoantibodies in increased platelet turnover, we assayed the plasma glycocalicin (GC) level and calculated the GC index for every patient. Our results provide direct evidence that an epitope located on platelet membrane glycoprotein IIb is recognized by PTCP-associated IgG antibodies; moreover GC levels in patients with EDTA-dependent PTCP were similar to control levels, thus excluding an increased platelet turnover. We conclude that antiplatelet antibodies directed against platelet cryptantigens are unlikely to have a major role in the increased removal of cells from circulation.

Antibodies, Monoclonal↗
PubMed1995

EDTA-dependent pseudothrombocytopenia: a clinical and epidemiological study of 112 cases, with 10-year follow-up.

In the past 10 years, we have observed 112 cases of EDTA-dependent pseudothrombocytopenia (PTCP) due to in vitro platelet clumping at room temperature. 93 patients had antiplatelet antibodies (48 IgM, 30 IgG, 3 IgA, and 12 had two different isotypes concomitantly). In 20% of patients, the presence of IgM antibodies characteristically accompanied platelet agglutination also at 37 degrees C, and in citrated blood. The phenomenon was not age or sex related, nor was it associated with any particular pathology or use of specific drugs, and was present in both healthy subjects and patients with various diseases. Flow cytofluorimetric analysis of CD5-positive B cells, which are responsible for autoantibody production, did not demonstrate any changes in the percentage and absolute number of this lymphocyte subset. Average follow-up was 5 years (6 months-10 years); however, previous clinical records disclosed that PTCP was present for more than 15 years in four cases, and more than 20 years in three others, with no clinical manifestation of disease. This study confirms that EDTA-dependent PTCP is a phenomenon related to the presence of natural autoantibodies with antiplatelet activity, devoid of pathological significance. Its clinical interest resides in the need for its prompt and certain recognition in order to avoid unnecessary examinations and therapeutic interventions. The best and most rapid technique for obtaining accurate platelet counts in PTCP subjects is to collect and examine EDTA blood at 37 degrees C; however, clumping will still be present in about 20% of these cases, and even in citrated blood. To obviate this phenomenon, blood should be collected in ammonium oxalate, and platelets counted in a Burker chamber.

Adolescent↗
PubMed1995

EDTA-dependent pseudothrombocytopenia. Association with antiplatelet and antiphospholipid antibodies.

In a study of 88 patients with EDTA-dependent pseudothrombocytopenia (PTCP), EDTA-dependent antiplatelet antibodies were seen in the sera of 72 (81.8%) patients (44 IgM, 25 IgG, and 3 IgA). The same sera also were tested for anticardiolipin antibodies (aCL), and 56 (63.6%) patients had sera that also were reactive for aCL (33 IgM, 21 IgG, and 2 IgA). The 16 patients who were negative for antiplatelet antibodies also were negative for aCL antibody. Overall concordance between antiplatelet and aCL antibodies was 82.9%; the correlation between antiplatelet and aCL antibody isotype distribution was 82.1%. Following cardiolipin absorption, most of the PTCP-sera were negative for antiplatelet activity, and no longer reproduced platelet clumping when incubated with normal blood. This finding showed that the antiplatelet antibodies cross-reacted with negatively charged phospholipids. However, after absorption on normal platelets, complete inhibition of aCL activity was observed in 34 (60.7%), and partial inhibition in 14 of the 56 patients who were aCL positive. These findings support the hypothesis that antibody subpopulations (naturally occurring autoantibodies) directed against negatively charged phospholipids can bind to antigens modified by EDTA on the platelet membrane, and may be responsible for PTCP genesis.

Absorption↗
PubMed1995

Platelet satellitism is Fc gamma RIII (CD16) receptor-mediated.

Platelet satellitism (PS), the phenomenon of platelet rosetting around polymorphonuclear neutrophils (PMN), which is observed in ethylenediamineetetraacetic acid (EDTA)-anticoagulated blood at room temperature, is caused by the presence of IgG autoantibodies in the serum. Fourteen patients with PS were studied, and the presence of both EDTA-dependent antiplatelet and EDTA-dependent antineutrophil IgG (auto)antibodies were found in their sera. Anti-neutrophil activity was completely abolished when the sera were absorbed on normal platelets, which suggests that a single antibody is involved. Inhibition studies with monoclonal antibodies indicated that this IgG autoantibody is directed against the glycoprotein IIb/IIIa complex of the platelet membrane, as well as the neutrophil Fc gamma receptor III (Fc gamma RIII). In addition, the antibody did not react with platelets from a patient with type I Glanzmann's disease, nor with neutrophils from a patient with congenital Fc gamma RIII absence (NAnull phenotype), thus confirming both specificities. As in other literature cases, a clear correlation between the presence of this IgG and a specific clinical situation, disease, or use of drugs could not be shown. Therefore, these antibodies, which are present in some normal individuals, might occur naturally. Because of the exposure of particular cryptoantigenic structures present on EDTA-modified platelet and PMNs, they may manifest themselves by triggering the PS phenomenon.

Antibodies, Monoclonal↗
PubMed1993

Alcohol induced burr cell (echinocytic) haemolytic anaemia and haemochromatosis.

A 51-year-old man with chronic alcoholic liver disease developed a severe haemolytic anaemia characterized by the presence of circulating burr-shaped cells (echinocytes). Several transfusions of packed red cells were ineffective in raising the haemoglobin concentration, showing that the abnormality was acquired by the transfused cells. Liver biopsies revealed haemochromatosis. Haematological parameters normalized four months after the patient stopped drinking alcohol, but burr cells were still present and erythrocyte life-span was still markedly shortened at one year follow-up. Since serum cholesterol, HDL-cholesterol, and Apo-AI and Apo-B lipoproteins were considerably decreased, the lipid composition of the red cell membrane was studied. Findings showed that echinocytosis occurred with no change in membrane cholesterol content, nor in cholesterol:phospholipid ratio, but with an alteration in the phosphatidylserine and phosphatidylinositol concentrations. While haemochromatosis was most likely the cause of the erythrocyte anomaly, alcohol intake was probably responsible for the acute onset of haemolytic anaemia with effects directly on the erythrocyte membrane as well as mediated by the progressive hepatic injury, with alterations in the plasma and successively in the intramembrane lipid composition.

Anemia, Hemolytic↗
PubMed1993

Myelosarcoma preceding acute leukemia diagnosed by fine needle lymph node aspiration: report of two cases.

Myelosarcoma (granulocytic sarcoma) is a rare tumor seen in patients with known hematologic malignancies such as leukemia, myelodysplastic syndromes and myeloproliferative disorders, as well as in non-leukemic patients. A correct diagnosis in these cases is often difficult, and these are more commonly misdiagnosed as large cell lymphoma. We describe two women, 40 and 89 years of age respectively, in whom a myelosarcoma involving the neck lymph nodes was diagnosed by cytological examination of a fine needle aspiration biopsy, one and 10 weeks before the onset of acute myelogenous leukemia. The fine needle aspiration technique allowed a quick and unexpected diagnosis to be made demonstrating granulocytic differentiation and the presence of myelo-monocytic cells within lymphatic tissue. The simplicity of the procedure, coupled with its reliability and rapidity suggest that fine needle aspiration biopsies should be used more widely as a first choice method in the diagnostic evaluation of palpable lymph nodes.

Adult↗
PubMed1993

Humoral response to subcutaneous, oral, and nasal immunotherapy for allergic rhinitis due to Dermatophagoides pteronyssinus.

We investigated variations in total IgE, and specific IgE, IgG, and IgG4 for Dermatophagoides pteronyssinus in 57 patients with perennial rhinitis due to house dust mite allergy in an open controlled study: 43 subjects received immunotherapy (17 subcutaneous, 14 sublingual, and 12 local immunotherapy) and 14 were controls. The results were compared with the clinical course to determine possible associations between serum and clinical changes. Subcutaneous, but not sublingual and nasal, immunotherapy induced a significant clinical benefit (P < .001). Specific antibody behavior in patients receiving subcutaneous immunotherapy was similar to literature reports. Specific IgE levels fell starting from the 6th month of therapy, and specific IgG and IgG4 levels rose significantly, but there was no correlation with the clinical course. The other two forms of immunotherapy did not induce significant specific antibody modifications. We conclude that the specific IgG4 rise induced by subcutaneous immunotherapy was the most important variation observed. This change, however, was not correlated with the clinical outcome.

Administration, Intranasal↗