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Biomedical subjects

R Coppo

Publications and source records attributed to R Coppo.

At least 73 records · Page 4Linked to original sources
PubMed1991

The fate of aggregated immunoglobulin A injected in IgA nephropathy patients and healthy controls.

Organ uptake of IgA-containing immunologically active material was studied in humans by intravenous (IV) injection of 131I-labeled heat-aggregated human secretory IgA (HAS-IgA) in nine patients affected by primary IgA nephropathy and 10 normal volunteers. Aggregated secretory IgA was found to be removed almost exclusively by the liver. The peak activity in liver was reached at 21.1 minutes (range, 18 to 26 minutes) in patients and 19 minutes (range, 14 to 22 minutes) in controls. The rate of increase of liver radioactivity was found to be significantly slower in patients (with a mean slope of 5.0; range, 3.4 to 7.1 v 7.6, 5.6 to 11.4; P less than 0.02). The mean liver to precordium ratio at the peak time was significantly lower in patients (mean value, 2.3; range, 1.9 to 3.1) compared with controls (mean value, 3.3; range, 2.4 to 4.0) (P less than 0.02). These data confirm the pivotal role of the liver in the removal of aggregated IgA in humans and the defective clearance capacity of this test probe in IgA nephropathy patients.

Adult↗
PubMed1991

IgA antibodies to dietary antigens and lectin-binding IgA in sera from Italian, Australian, and Japanese IgA nephropathy patients.

We studied serum IgA as antibodies to dietary antigens (Ag), as lectin-binding molecules, and as conglutinin-binding immune complexes (IgAIC) in people from geographical areas in which IgA nephropathy (IgAGN) is particularly frequent. Sera from 63 Italian, 21 Australian, and 25 Japanese patients affected by IgAGN and 24 Italian, 20 Australian, and 40 Japanese healthy controls were studied. Increased values of IgAIC were detected in 42.8% of Italian patients, while only in 23.8% and 8% of Australian and Japanese patients, respectively. Mean values were significantly increased only in Italian patients (P less than 0.0001). Positive values of IgA antibodies against dietary Ag had variable prevalences, but again Italian patients showed the highest frequency, from 19% to 28.5% versus 0 to 38% in Australians and 0 to 16% in Japanese. Mean values of these antibodies were not significantly increased in any patient groups in comparison to the corresponding healthy populations. However, patients with elevated values of IgAIC had significantly higher serum concentrations of antibodies to alimentary components and a linear correlation was found between IgAIC and some IgA antibodies to food components. The relationship between these two series of data was particularly evident for Italian and Australian IgAGN patients. Moreover, the patients with positive data tended to have a cluster of increased levels of IgA antibodies against several alimentary Ag at the same time. A linear correlation was evident between values of IgA antibodies to gluten fractions and to heterologous albumins. None of these correlations was evident among healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Classic and perinuclear anti-neutrophil cytoplasm antibodies and antimyeloperoxidase antibodies in rapidly progressive glomerulonephritis.

Classic anti-neutrophil cytoplasm antibodies (cANCA), perinuclear ANCA (pANCA) and antibodies directed against myeloperoxidase (MPO-Ab) were evaluated in 25 patients with either idiopathic or secondary rapidly progressive glomerulonephritis (RPGN). While cANCA were found almost exclusively in Wegener's granulomatosis, pANCA were detectable in several disorders, including microscopic polyarteritis (mPA), but also idiopathic RPGN. MPO-Ab were frequently found in sera from patients with all types of idiopathic but not of secondary RPGN. These results support the hypothesis that some cases of RPGN are early or limited forms of systematic vasculitis. We then looked for the presence of IgA-ANCA in Henoch-Schoenlein purpura (HSP): we found IgA-ANCA with immunoenzymatic assay but not with immunofluorescence in HSP, in primary IgA-GN and in membranous GN as well, thus suggesting the poor specificity of this type of ANCA. The possible pathologic implications of ANCA were examined in vitro. Serum samples from several patients with ANCA were assessed for their capacity to enhance chemiluminescence generation from resting or PMA-stimulated macrophages. Sera from RPGN and mPA patients displaying anti-MPO activity induced granulocytes to enhance the production of oxygen free radicals, thus suggesting a phlogistic effect of MPO-Ab positive sera.

Adult↗
PubMed1991

Immune material processing by phagocyte cell system in cryoglobulinemia.

An impaired function of splenic macrophages, measured as the clearance rate of erythrocytes coated with IgG (E-IgG), was observed in 7 out of 8 cryoglobulinemic patients with severe urinary abnormalities and systemic symptoms, and in 0 out of 6 patients without urinary symptoms and only mild systemic signs of disease. The E-IgG clearance rate was not related to HLA or Rh phenotype, patients' age or disease duration. Moreover, longitudinal studies showed this parameter to be strictly related to disease activity. To investigate the nature of the defect, five series of analyses were planned using peripheral blood phagocytes (PBP) from 8 patients: a) detection of cell-bound immune material by using the antibody CE59 directed to the Fc fragment of IgG modified by the antibody-antigen reaction; b) cytofluorometric and/or radiometric analyses of the cell surface expression of HLA II, CR1 and FcR structures by means of specific monoclonal antibodies (MoAbs); c) electron microscopy (EM) examination of diverse combinations of cryoglobulins incubated with PBP from patients and normals; d) analysis of cryoglobulin-induced inhibition of E-IgG phagocytosis; e) measurement of the generation of chemiluminescence (CL) in response to Zymosan, Phorbol Myristate Acetate and n-Formyl-Methyonine-Leucine-Phenilalanine (n-FMLP). Patients' PBP were found to have a higher amount of cell-bound immune material as compared to normals (p less than 0.01). CR1 and FcR expression was not different from controls, whereas a slight increase in percentage of monocytes bearing HLA II structures was found in patients (p less than 0.05). Upon EM examination no obvious differences were found in the internalization capacity of cryoglobulins between patients and controls. The CL production was lower than normal (p less than 0.02), whatever stimulus used, with a maximal impairment for n-FLMP (p less than 0.005), the most specific test probe for cytoskeleton integrity. Finally, a remarkable cryoglobulin-induced inhibition of E-IgG phagocytosis was shown. A combination of saturation mechanisms and intracellular abnormalities could underlie the apparent discrepancy between E-IgG clearance defect and preserved potential of cryoglobulin internalization in cryoglobulinemia.

Adult↗
PubMed1990

Monoclonal gammopathy and glomerulonephritis with organized microtubular deposits.

We report a case with IgG-kappa monoclonal gammopathy of unidentified significance (MGUS) and glomerulonephritis (GN) with organized microtubular deposits on electron microscopy (EM). Light microscopy (LM) examination showed exudative features and moderate extracapillary proliferation. An acute nephritic syndrome with a rapidly progressive renal failure was clinically manifest at the onset and during each relapse. The patient was treated with methylprednisolone pulses followed by oral prednisone, cyclophosphamide, plasmapheresis, and maintenance courses of chemotherapy. The response to treatment was good, with a temporary improvement of renal function and control of the downhill course over a 3-year follow-up.

Adult↗
PubMed1990

Erythrocyte Na,Li countertransport and arterial pressure in diabetic adolescents.

The aim of this study was to analyze Na,Li countertransport in erythrocytes from adolescents with insulin dependent diabetes mellitus (IDDM) and to see if those with elevated values present distinct clinical features, in particular as regards arterial pressure and urinary albumin excretion (UAE). Twenty-nine adolescents with IDDM (17 males, 12 females, mean age 15 +/- 0.6 years, mean diabetes duration 11.4 +/- 0.7 years) and fifteen healthy age-matched control subjects (8 males, 7 females, age 14.5 +/- 1 years) were investigated. Diabetic adolescents had a RBC Na,Li countertransport activity higher than age matched normal controls; geometric mean 283 (95% limits 259-340) vs. 193 (169-252) mumol/l RBC/h; p less than 0.01. Seven out of 29 subjects had values higher than the 95th percentile of normal subjects (Counter +). Both systolic and diastolic arterial pressures were significantly higher in Counter + than in Counter - patients. No significant differences were found as regards age, body mass index, diabetes duration, HbA1c, fructosamine, serum potassium, triglycerides, creatinine clearance and UAE. The logarithm of systolic pressure was independently positively correlated with ln Na,Li countertransport (r = 0.38; p less than 0.05), ln [Nai] (r = 0.38; p less than 0.05), and ln body mass index (r = 0.5; p less than 0.01) in diabetic patients. The main finding of this study is that diabetic adolescents with a high erythrocyte Na,Li countertransport rate have an arterial pressure significantly higher than patients with normal Na,Li countertransport fluxes.

Adolescent↗
PubMed1990

Wheat protein antigens and effector cells of aspecific immunity.

The effects of gliadin and glyc-gli on leukocyte chemiluminescence response, cytotoxic activity and locomotion were assessed in vitro. A dose-dependent increase in chemiluminescence response of neutrophils stimulated by Zymosan was observed by using gliadin at concentrations ranging between 1 and 20 micrograms. By increasing glyc-gli concentrations, a bimodal response was observed with an enhancement up to 50 micrograms/ml, followed by dose-dependent suppressive effects. The cytotoxic activity of a suspension of peripheral blood mononuclear cells on the human myeloid line K562 was assessed in a Chromium release assay. By pretreating effector cells with optimal doses of gliadin (5 micrograms/ml) or glyc-gli (50 micrograms/ml), an enhancement of cytotoxic activity, similar to that of the gamma-Interferon, could be achieved. Finally glyc-gli was found to elicit neutrophil chemokinesis. The possible implications of these findings in diseases characterized by gluten intolerance are discussed.

Adult↗
PubMed1990

Effects of a gluten-free diet in primary IgA nephropathy.

In an uncontrolled study a gluten-free diet was given to 29 patients affected by primary IgA nephropathy (IgAGN). All of them followed the diet for 6 months, 23 patients for 1 year and 9 for 2 to 4 years. Mean levels of IgA containing circulating immune complexes (IgAIC), detected by a specific conglutinin assay and by measuring IgA content in 2.5% polyethylene glycol precipitates, on an unrestricted diet, significantly decreased after 6 months of gluten-free diet (p less than 0.01) and remained reduced during the follow-up. A decrease in IgAIC levels was evident in 85.7% of the cases with basal positive data, with complete normalization in 64.3% of them. IgA to gluten antigens (ethanol- or saline-soluble gliadin, glutenin and the lectin fraction termed glyc-gli) as well as to heterologous bovine and egg albumins were found to be significantly increased on an unrestricted diet in the group of 14 IgAGN patients with basal positive IgAIC. The mean levels of IgA to most dietary antigens significantly decreased after 6 months to 1 year of a gluten-free diet. A decrease in IgA to ethanol-soluble gliadin was evident in 81.8% of the cases with basal positive data, with complete normalization in 63.6%. A subgroup of 27.5% of IgAGN patients showed positive IgAIC values associated with increased IgA values to a variety of dietary antigens. A gluten-free diet induced in 75% of the cases a parallel improvement in these abnormal immunological data. Mean proteinuria values were found to be significantly decreased after 6 months of the diet and a reduction was also observed in microscopic hematuria. However, mean blood creatinine levels showed a significant increase after the gluten-free diet. The data of this study indicate that a gluten-free diet can modify some immunological abnormalities in a group of IgAGN patients, reducing levels of IgAIC and IgA to dietary antigens. The clinical course does not seem to be favorably influenced, since a relentless progression towards renal failure was observed.

Adult↗
PubMed1989

Clearance of polymeric IgA aggregates in humans.

Clearance of aggregated human secretory immunoglobulin A (AHS-IgA) was studied in nine patients affected by primary IgA nephropathy (IgAGN) and six normal volunteers from the medical staff. Samples of whole blood, erythrocytes, and serum were taken from 3 to 120 minutes after injection of 0.5 mg of 131iodine-labeled AHS-IgA. No significant radioactivity was recorded on erythrocytes. The clearance curve of AHS-IgA from the circulation, calculated by measuring trichloroacetic acid precipitable radioactivity in serum, was found to be biexponential with an initial fast component significantly prolonged in patients (mean half-time, 19.4 minutes, range, 14 to 26 minutes) compared with controls (mean, 12.2 minutes, range, 7.6 to 16.8 minutes; P less than 0.01). These data indicate that clearance of aggregated polymeric IgA does not involve the erythrocyte transport system and seems to be defective in IgAGN patients.

Adult↗
PubMed1989

Functional changes of monocytes due to dialysis membranes.

The functional effects directly induced by dialysis membranes on peripheral monocytes were analyzed in a plasma-free model of simulated dialysis using Cuprophan, cuprammonium rayon, polyacrylonitrile, polymethylmetacrilate and polysulphone membranes. A severe reduction of monocyte phagocytosis of IgG-coated erythrocytes was found by using Cuprophan and cuproammonium rayon. The cytofluorimetric analysis of several cell surface receptors, involved in the immune phagocytosis and recognizable by five quoted monoclonal antibodies, did not reveal any significant change. The defective phagocytosis of the IgG-coated erythrocytes by monocytes, due to the exposure to cellulose-derived membranes, was paralleled by an impaired interiorization of heat-aggregated human immunoglobulins, as analyzed by electron microscopy. The cell membrane binding of aggregated immunoglobulins was found to be unaffected. The defect was associated to a remarkably depressed generation of reactive oxygen species after Zymosan stimulation. Therefore, the defective immune phagocytosis induced by exposure of monocytes to cellulosic membranes was not due to a receptor rearrangement or an impaired binding of ingestible particles, but to a reduced internalization capacity probably related to an energy source exhaustion (as shown by the lack of response to stimuli able to induce oxidizing species production). These features are similar to those described in monocytes from acute systemic lupus erythematosus patients.

Cell Survival↗
PubMed1989

Complement receptor (CR1) and IgG or IgA on erythrocytes and in circulating immune complexes in patients with glomerulonephritis.

This study reports the quantitative analysis of complement receptor (CR1) molecules on erythrocyte surface, the amount of immunoglobulin-containing material (IgG-IC and IgA1-IM) on the erythrocyte surface, and the concentrations of circulating immune complexes (IgG-CIC and IgA-CIC); also reported are the HLA phenotypes of 44 patients affected by various forms of glomerulonephritis (including 20 primary IgA nephropathy, 11 membranous glomerulonephritis, 9 lupus nephritis and 4 renal vasculitis). Erythrocyte CR1 molecules were found to be decreased (P less than 0.02) and erythrocyte IgG-IC were less than in controls (P less than 0.025) in lupus nephritis patients, whereas IgG-CIC were significantly greater (P less than 0.02). In patients affected by primary IgA nephropathy, mean erythrocyte CR1 concentrations were significantly decreased (P less than 0.02). Patients with impaired renal function had mean erythrocyte CR1 values significantly greater than those with normal renal function (P less than 0.002). Immunoglobulin-containing material on the erythrocyte surface was not significantly increased, whereas the serum concentrations of both IgA-CIC and IgG-CIC were significantly increased (P less than 0.02). In membranous nephropathy erythrocyte CR1 molecules were quantitatively similar to control data and no increase in CIC was observed. Conversely, erythrocyte IgG-IC were significantly increased (P less than 0.01). No significant relationship among erythrocyte CR1 molecules, erythrocyte surface-associated immunoglobulins, CIC, and HLA phenotype was observed in any patient group.

Adult↗
PubMed1989

Phenotypic and functional analysis of circulating phagocytic cells in IgA nephropathy patients.

We analysed the possible mechanisms responsible for the functional abnormalities reported on phagocyte cell function in IgA nephropathy patients. The oxidative metabolism by the superoxide anion ferricytochrome C reduction test on monocytes and the chemiluminescence response on neutrophils was examined in 32 patients. Moreover the expression of cell membrane structures involved in immune response and phagocytosis (i.e. Fc receptors and HLA class II antigens) was evaluated cytofluorimetrically using specific monoclonal antibodies. Our own results did not show striking differences in oxidative potential and phenotype of patients' phagocyte cells as compared with healthy controls. However a HLA class II-associated structure was found to be quantitatively more expressed in patients' monocytes than in normal controls (P less than 0.005). These findings suggest that the defective phagocyte system function reported in IgA nephropathy patients is not simply due to a loss of cell surface receptors, nor to abnormalities in intracellular metabolic pathways implying oxygen consumption. The increase in expression of some HLA class II structures, often associated with the presence of circulating IgA immune complexes, probably reflects a protracted immunological stimulation.

Adolescent↗
PubMed1989

Gluten-induced experimental IgA glomerulopathy.

The effect of alimentary gluten and of its lectin-like fraction gliadin in inducing IgA mesangial deposits in BALB/c mice was investigated. In the pilot study G1 (4 mice), G2 (4 mice) and G3 (6 mice) received ovalbumin, human gamma-globulins, and crude gluten, respectively. The antigens, 1 mg/ml, were given in drinking water for 14 weeks. G4 (20 mice) were fed with standard mouse fodder. Gluten, as well as other alimentary antigens, induced IgA mesangial deposits with intense IgA staining in each animal, however a positive IgA staining was also observed in 10 of 20 adult controls. Antigliadin IgA antibodies were detected in renal tissue eluates from gluten-immunized mice but were found in eluates from control animals too. IgA deposits and antigliadin IgA in renal tissue were also observed in 3 of 7 adult mice (G7) fed for 30 weeks with standard fodder, then for 1 month with a protein-free diet supplemented with 20% amino acids. Conversely, there were no IgA mesangial deposits or IgA anti-gliadin antibodies in renal eluates of 1- or 2-week-old mice (G5 and G6). For the definitive protocol, 4-week-old BALB/c mice were selected and fed with basal glutenfree diet. G8 (14 mice) did not receive any alimentary immunogen in the drinking water, whereas G9 (15 mice) and G10 (15 mice) received ovalbumin and gliadin, respectively. G11 (15 mice) had standard gluten-containing diet. IgA deposits semiquantified by immunofluorescence scores were found to be significantly greater in G9 and G10 than in G8 (Student' t-test p1 less than 0.003, Mann-Whitney test p2 less than 0.001 and p1 less than 0.01, p2 less than 0.007, respectively), and in G11 than in G8 (p1 and p2 less than 0.05). The presence of positive IgA staining (greater than or equal to 2/6 scores) was significantly less frequent in G8 in comparison to G9 (chi-square test p3 less than 0.002), G10 (p3 less than 0.02) and G11 (p3 less than 0.04). Total serum IgA were significantly higher in orally immunized G9 and G10 than in G8 control mice (p1 less than 0.005, p2 less than 0.002). Anti-gliadin IgA in circulation as well as in renal deposit eluates were significantly increased in gluten-eating mice (G10 and G11) as compared with the gluten-free control group G8. These observations indicate that gliadin does induce IgA immune deposits in BALB/c mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Single kidney function: effect of acute protein and water loading on microalbuminuria.

The hyperfiltration induced by an acute response to an oral protein and water load was investigated to ascertain whether it can modify the urinary albumin excretion (UAE) in the microalbuminuric range by further increasing the glomerular filter permeability. To this end, six patients with a single kidney selected as having microalbuminuria on a regular diet without the clinical or laboratory data of overt renal disease and eight healthy subjects received a short-term protein and water load (150 g of meat-derived protein and 1 liter of water). In patients with one kidney, mean basal UAE values were significantly higher than in control subjects (p less than 0.006), whereas endogenous creatinine clearance values were only slightly lower (p greater than 0.05). One hour after the protein and water load, an abrupt increase in microalbuminuria levels was found in patients with one kidney and mean UAE values were significantly higher than in control subjects (p less than 0.002), whereas mean creatinine clearance values were significantly lower in patients than in control subjects (p less than 0.01). High UAE (p less than 0.002) and low creatinine clearance (p less than 0.002) values were maintained over the following four hours in patients with one kidney. These data suggest that in the single kidney with reduced renal functional reserve, an oral protein and water load magnifies the pre-existing loss of glomerular permselective properties due to chronic hyperfiltration as manifested by a further increase in microalbuminuria.

Adult↗
PubMed1988

The pathogenetic potential of environmental antigens in IgA nephropathy.

Patients with IgA nephropathy (IgAN) can be considered high responders for IgA production; data which indicate a generalized hyperreactivity of the immune system include autoantibody production, increased response to viral vaccination, and high titers of antibodies to various common respiratory and gastrointestinal microbes. From clinical and experimental observations, two types of antigen seem to be most involved in the pathogenesis of IgAN, ie, environmental respiratory or gastrointestinal infectious agents and dietary antigens. A role played by microbes has been suggested because macroscopic hematuria shortly follows a pharyngitis or a gastrointestinal disturbance. Antibodies to a wide spectrum of viral and bacterial infectious agents have been detected in sera from patients with IgAN. The possible role of dietary antigens has been demonstrated experimentally in animal models. In human IgAN, antibodies to various dietary antigens have been detected in sera; antibodies have also been found in IgA immune complexes and renal eluates. In human IgAN, a significant decrease in serum levels of IgA-containing circulating immune complexes after a gluten-free diet has been observed. The present experience accounts for 27 IgAN patients followed for 6 months to 3 years on a gluten-free diet. A decrease in serum levels of IgA-containing circulating immune complexes was observed in 64% of the patients whose initial levels were high during a period of unrestricted diet. Patients with basal high levels also had significantly high levels of IgA antibodies to dietary antigens, including bovine serum albumin, ovalbumin, and various gluten fractions. After 1 year of gluten-free diet the levels significantly decreased. A disappearance of antigliadin IgA, observed in 80% of the cases, was paralleled by a decrease in titers of the other antibodies to dietary components. These data support the hypothesis that in patients with IgAN, gluten may act as a toxic lectin, increasing the permeability of the intestinal mucosa to various dietary antigens.

Animals↗