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Biomedical subjects

F Biagi

Publications and source records attributed to F Biagi.

At least 37 records · Page 2Linked to original sources

A non-toxic analogue of a coeliac-activating gliadin peptide: a basis for immunomodulation?

BACKGROUND: A-gliadin residues 31-49 (peptide A) binds to HLA-DQ2 and is toxic to coeliac small bowel. Analogues of this peptide, which bind to DQ2 molecules but are non-toxic, may be a potential route to inducing tolerance to gliadin in patients with coeliac disease. METHODS: Toxicity was investigated with small bowel organ culture in six patients with untreated coeliac disease, four with treated coeliac disease and six controls. Analogue peptides comprised alanine substituted variants of peptide A at L31 (peptide D), P36 (E), P38 (F), P39 (G) and P42 (H). RESULTS: Peptides D and E were toxic in biopsies from some patients. Peptides F, G and H were not toxic. CONCLUSIONS: Peptide F, which binds to DQ2 more strongly than peptide A, is not toxic in patients with coeliac disease in-vitro; this could be an initial step towards investigation of the induction of tolerance to gliadin in patients affected by coeliac disease.

Adult↗

Transglutaminase and coeliac disease: endomysial reactivity and small bowel expression.

This study was aimed at verifying whether tissue transglutaminase (tTG) is the sole autoantigen eliciting anti-endomysial antibodies in coeliac disease (CoD) and investigating tTG expression in normal and coeliac mucosa. Twelve anti-endomysial-positive coeliac sera and 12 anti-endomysial-negative control sera (10 microl, diluted 1:5-1:400 in PBS pH 7.3) were preincubated with 10, 20 or 50 microg guinea pig liver tTG at 4 degrees C overnight. Monkey oesophagus tissue slides were then tested with tTG-preincubated and non-preincubated sera to search for IgA anti-endomysial reactivity by indirect immunofluorescence. Moreover, six sections of monkey oesophagus were incubated with an anti-tTG mouse MoAb, six sections with an anti-cytokeratin mouse MoAb and six sections with only 3% bovine serum albumin. Finally, endoscopic duodenal biopsy sections obtained from 12 patients affected by untreated CoD, six patients affected by treated CoD and 10 biopsied controls were immunohistochemically stained with a peroxidase-conjugated anti-tTG MoAb. Our results show that (i) preincubation with tTG abolished endomysial immunofluorescence in most, but not in all, coeliac sera; (ii) the incubation of anti-tTG MoAb with sections of monkey oesophagus resulted in an immunofluorescence staining pattern similar but not identical to that of anti-endomysial-positive coeliac sera; (iii) although tTG expression was present at muscularis mucosae and pericryptal fibroblast in both normal and coeliac mucosa, it was slightly more marked and evident in the latter. Although our absorption experiment was performed with guinea pig liver tTG, we confirm that tTG is the predominant antigen of endomysial antibodies, but we speculate that, at least in some patients, it is not the only one.

Animals↗

Is gliadin mispresented to the immune system in coeliac disease? A hypothesis.

The primary pathogenic trigger in coeliac disease (CD) is still unknown. We present the hypothesis that in CD the enterocytes could metabolize gliadin through an immunogenic pathway instead of a tolerogenic one. The result of this abnormal presentation of gliadin to the immune system would be the activation of lamina propria T cells, followed by the onset of enteropathy.

Antigen-Presenting Cells↗

Tissue transglutaminase antibodies in celiac disease.

OBJECTIVE: Tissue transglutaminase is the antigen for antiendomysial antibodies, whose power in screening for celiac disease is well known. Our aim was to assess the efficacy of an ELISA assay for tissue transglutaminase antibodies. METHODS: Tissue transglutaminase antibodies were analyzed in serum from 39 untreated celiac disease patients and 61 controls. Tissue transglutaminase was used as antigen, and test sera analyzed by ELISA. Results higher than 0.6 optical density were considered positive, lower than 0.4 negative, and between 0.4 and 0.6 borderline. RESULTS: Optical density of the serum from the patients with untreated celiac disease (median: 1.41; range: 0.33-1.47) were significantly higher than the controls (median: 0.32; range: 0.17-0.68; p < 0.0001; 95% confidence interval 0.87-1.08). Thirty-three patients with untreated celiac disease were positive, 4 borderline, and 2 negative. Fifty-five controls were negative, 4 borderline, and 2 positive. If we consider borderline results to be positive, sensitivity is 94.8% and specificity 90.1%. None of the controls gave results higher than 0.7 optical density. Apart from the 2 negative patients with untreated celiac disease, the two groups overlapped only between 0.4 and 0.7 optical density. CONCLUSIONS: Because of the high sensitivity (approximately 95%) and technical simplicity, tissue transglutaminase antibodies may prove useful for the screening of celiac disease in population at low or medium risk of celiac disease. To avoid duodenal biopsies in patients without celiac disease, the specificity of the screening procedure may be increased by confirming with antiendomysial antibodies by immunofluorescence on human umbilical cord in individuals with results between 0.4 and 0.7 optical density.

Adolescent↗

Proliferating cell nuclear antigen expression is increased in small bowel epithelium in the elderly.

Although previous studies suggest that in aging animals the small intestine is in a hyperproliferative state, no information is currently available on the influence of age on the proliferation pattern of human small bowel enterocytes. The immunohistochemical expression of the proliferating cell nuclear antigen (PCNA), the villous height to total mucosal thickness ratio and the enterocyte height were evaluated in a panel of duodenal biopsy specimens obtained from 18 subjects aged less and 14 subjects aged more than 65 years. There was a significant positive correlation (P < 0.001) between age in years and percent of positive PCNA enterocytes both at the level of crypts (rs = 0.50) and villi (rs = 0.77). Moreover, the percentage of PCNA+ enterocytes was significantly higher in elderly versus adult subjects, both at the level of villi (6.5 vs 0%; P < 0.001) and of crypts (40.0 vs 23.7%; P < 0.01). No correlation was found between the percentage of PCNA + enterocytes and enterocyte height or villous height to total mucosal thickness ratio. Our results show that PCNA reactivity increases with advancing age both in crypts and villi. This abnormality of the proliferation pattern may explain the coexistence of normal morphology and impaired absorptive function in the elderly.

Adult↗

Splenic function in old age.

Hyposplenism has been reported in elderly people. However, from previous studies, it was not clear whether the observed alterations in splenic function were a physiologic effect of advanced age itself or a consequence of age-related diseases. As hyposplenism is believed to predispose to infections, autoimmune phenomena and thrombosis, this question is of great clinical concern. In the present study splenic function was assessed by counting the pitted red cells in 65 healthy subjects aged 50-108 years. At variance from previous studies, our study population consisted of free-living individuals carefully selected in order to exclude any underlying disease. The percentage of pitted red cells in 37 subjects over 70 years was significantly higher than in 28 younger subjects, although only 1 subject had a pitted red cell count indicating splenic hypofunction. A positive, but weak, correlation between the percentage of pitted red cells and age was also found when considering the whole population (rs = 0.273, p = 0.029). In conclusion, although slightly reduced with advancing age, splenic function seems basically to be maintained in elderly people.

Aged↗

Autoimmune enteropathy and villous atrophy in adults.

BACKGROUND: Autoimmune enteropathy is a condition described in children and characterised by villous atrophy, which is unresponsive to any dietary restrictions, and by the presence of enterocyte autoantibodies. We report two adult patients who fulfilled all the criteria for the diagnosis of this disorder. METHODS: Over the past 5 years we have seen four adult patients (all women, median age 51.5 [range 38-64] years) with subtotal villous atrophy, which was unresponsive to a gluten-free diet. The patients were HLA-DQ2 positive. IgA antigliadin and antiendomysial antibodies were not found in any of the patients. We did an indirect immunofluorescence search for enterocyte autoantibodies on monkey jejunum and for other autoantibodies for all four patients. FINDINGS: Of the four patients, two were positive for enterocyte autoantibodies and one of these two patients was positive for antiactin, antiparietal cell, and antithyroid microsomal autoantibodies. INTERPRETATION: To the best of our knowledge the two patients affected by severe enteropathy, who had never responded to any exclusion diet, and who were positive for enterocyte autoantibodies are the first cases of autoimmune enteropathy described in adults. We propose that adult patients whose disorders are unresponsive to a gluten-free diet should be tested for enterocyte autoantibodies.

Actins↗

The smaller size of the 'coeliac iceberg' in adults.

BACKGROUND: Since it has been ascertained that the prevalence of coeliac disease in the general paediatric population is 3.3 per 1000, we decided to evaluate this prevalence in the general adult population. METHODS: Two thousand two hundred and thirty-seven adult subjects aged 20-87 years, representative of a population with sociodemographic characteristics typical of Western European countries with regard to sex and age, were studied. In all serum IgA antiendomysial antibodies (EMA) were searched for, and all patients who turned out to be positive underwent intestinal biopsy. RESULTS: Four symptomless subjects aged between 20 and 39 years proved positive at the IgA EMA screening. This intestinal biopsy confirmed coeliac disease in all of them. The prevalence in our study group was, therefore, 1.8 per 1000. CONCLUSIONS: This study shows that the size of the submerged part of the 'coeliac iceberg' is perhaps smaller in the adult population and suggests a linear trend towards a lower coeliac disease prevalence as age increases.

Adult↗

[Electrogastrography. Evolution and clinical applications].

Electrogastrography (EGG) is a non invasive technique of recording gastric myoelectrical activity by cutaneous electrodes. Although first reported about 70 years ago, the development of this methodology has been very slow, mainly because of several shortcomings in data acquisition, interpretation of EGG data and poor correlation with the antral contractile activity. Recently, EGG has received increasing interest and technical improvements. The better quality of the signal obtained and the applications with automated signal processing, have improved the interpretation of the EGG. For this reasons, the number of EGG applications, both experimental and clinical, has rapidly increased. However, the lack of invasivity of this methodology has suggested some clinical applications which probably exceeded the specific possibility of the EGG. We aimed in this study at analysing several parameters, whose clinical relevance is not clearly understood, obtained by the automatic analysis, to identify patients with gastric electrical abnormalities between 10 patients with abnormal gastric emptying and 10 healthy controls. The best separation between these two groups was obtained by combining both mean dominant frequency and power.

English Abstract↗

Splenic function and alcohol addiction.

Severe hyposplenism has been recently documented in alcoholic liver disease, and it has been suggested that alcohol itself is important in the derangement of splenic function, despite a lack of evidence of a direct toxic effect of alcohol on the spleen. The aim of the present study was to assess splenic function in alcoholic patients without severe liver disease and to correlate these data with the degree and duration of alcohol intake. Fifty-two alcoholics, 31 subjects with current alcohol abuse (group A)-13 abstinent from alcohol for 1 to 6 months (group B) and B abstinent from alcohol for 6 months to several years (group C)- and 26 healthy social drinkers were studied. Splenic function was assessed by counting the percentage of pitted red cells. An in vitro experiment was performed to verify whether the presence of pitted red cells could be due to an effect of alcohol on red cell morphology. The percentage of pitted red cells in subjects from group A was significantly higher than in subjects from group B (p < 0.01), from group C (p < 0.005), and from controls (p < 0.001). There was no significant difference between group B, group C, and controls. Ten subjects from group A and 1 from group B and no subject from group C had evidence of splenic hypofunction. There was no significant correlation between the percentage of pitted red cells and daily alcohol intake or years of alcohol addiction. In conclusion, our study shows that, in patients with alcoholism but without any severe liver damage, a significant but slight increase in pitted red cells is present. Further studies are needed to clarify whether this is due to a mild form of splenic hypofunction or merely indicates erythrocyte membrane alterations.

Adult↗