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F Biagi

Publications and source records attributed to F Biagi.

At least 19 recordsLinked to original sources
PubMed2006

Transglutaminase 2 in the enterocytes is coeliac specific and gluten dependent.

BACKGROUND: Tissue transglutaminase, the coeliac autoantigen, was shown to localise in the enterocytes of coeliac patients and controls. It was speculated that surface tissue transglutaminase has a role in the pathogenesis of coeliac disease. AIMS: To study localisation of tissue transglutaminase in different stages of coeliac disease and other enteropathies with and without villous flattening. METHODS: Immunofluorescent and immunoblotting assays were used. Duodenal cryostat sections from 23 coeliac patients (10 untreated, 8 treated, 5 potential) and 18 controls (2 autoimmune enteropathy and 16 normal duodenal mucosa) were incubated with an anti-tissue transglutaminase monoclonal antibody. Slides were blindly examined. RESULTS: The immunofluorescent assay showed that monoclonal antibody localised in the subepithelial layer, in the lamina propria, and in the pericryptal connective tissue of all samples. It also bound to surface enterocytes in 8/10 untreated, 1/8 treated, and 3/5 potential coeliac patients. None of the controls showed an epithelial distribution of tissue transglutaminase. Immunoblotting experiments performed in enterocytes freshly isolated from duodenal biopsy confirmed these findings. CONCLUSION: Epithelial distribution of tissue transglutaminase is specific for coeliac disease rather than due to a non-specific mucosal inflammation. Analysis of different stages of coeliac disease suggests that the epithelial distribution of tissue transglutaminase is gluten dependent.

Adult↗
PubMed2005

Structural and functional abnormality of systemic microvessels in cardiac syndrome X.

BACKGROUND AND AIM: Microvascular damage of coronary bed has been considered the main pathogenetic factor of cardiac syndrome X (chest pain, exercise-induced ischemic ST-segment changes and angiographically normal coronary arteries). Previous studies have demonstrated that vascular abnormalities are not confined to the heart, suggesting a peripheral vascular dysfunction. On the hypothesis of a generalized microvascular disturbance in cardiac syndrome X, we performed a morphologic and functional study of systemic microcirculation in patients with syndrome X compared to normal subjects. METHODS AND RESULTS: Microvessels were evaluated with intravital videocapillaroscopy (VCP) executed in peripheral and conjunctival observation sites which explore micro and paramicrocirculation; biohumoral study included markers of inflammation and of endothelial function, coagulative-fibrinolytic system and lipid metabolism. Videocapillaroscopy showed several morphologic changes (present in high percent of patients with syndrome X and not in controls) and significant quantitative alterations (capillary density, granular flow score, alterations of vessel profile, length of capillary loop branches and of arteriole/venule diameter) which indicated a severe alteration of whole vessel structure and an important rearrangement of microvascular disposition. In a similar way, the humoral study showed some significant changes of endothelial (vWF, ICAM-1, E-sel, PAI-1), inflammatory (C-reactive protein (CRP), fibrinogen) and metabolic factors (HDL-chol) which are commonly associated with inflammatory response. CONCLUSIONS: We conclude that patients with cardiac syndrome X exhibited some structural and functional alterations of systemic microvasculature; the pattern is similar to that detected in systemic inflammatory diseases and suggests a vascular lesion of inflammatory type. The same changes could be operating also in coronary microvessels of patients with syndrome X.

Angina Pectoris↗
PubMed2004

Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease?

BACKGROUND: The counting of intraepithelial lymphocytes (IELs) in the villous tips of architecturally normal small bowel biopsy specimens was proposed as a method to measure mucosal infiltration in gluten sensitive patients. AIMS: To apply this straightforward method in duodenal biopsy specimens from patients affected by potential coeliac disease (PCD) to verify whether it can discriminate these patients from controls. METHODS: Paraffin wax embedded duodenal sections from 11 patients affected by PCD were stained with an antihuman CD3 antibody. Sections from 19 patients affected by treated coeliac disease (TCD) and 17 patients in whom coeliac disease was excluded were stained with the same antibody to serve as controls. The slides were examined blindly. IELs/20 enterocytes in five randomly chosen villous tips were counted. Patients affected by PCD were all on a gluten containing diet. They had an architecturally normal duodenal mucosa and were positive for endomysial antibody. Both TCD and non-coeliac controls were negative for endomysial antibody. RESULTS: The mean villous tip IEL scores were 4.6 (SD, 1.5; range, 1.4-7.8) in non-coeliac controls, 7.9 (SD, 4.0; range, 2.0-18.6) in TCD, and 9.2 (SD, 4.7; range, 5.8-21.8) in patients with PCD. The difference between PCD and non-coeliac controls was significant. CONCLUSIONS: This is a very simple and sufficiently reliable method to count IELs. In patients with an architecturally normal duodenal mucosa, the IEL count in villous tips helps to distinguish between patients with PCD and non-coeliac controls.

Adolescent↗
PubMed2003

In patients with dermatitis herpetiformis distribution of transglutaminase in cutaneous tissue does not differ from controls.

BACKGROUND: Dermatitis herpetiformis may be regarded as the cutaneous counterpart of coeliac disease. These conditions are related to the ingestion of gluten and both are characterised by circulating antibodies against tissue transglutaminase. AIMS: To study the distribution of tissue transglutaminase in the skin of dermatitis herpetiformis patients and controls, and to investigate whether the dermal IgA deposits, diagnostic for dermatitis herpetiformis, are related to tissue transglutaminase expression in the skin. METHODS: A series of 11 patients with dermatitis herpetiformis had a 4 mm punch biopsy taken from the uninvolved perilesional skin. A group of 16 controls, undergoing surgical removal of benign nevi, gave perilesional skin. Biopsies were covered with OCT and frozen at -80 degrees C. After washing, skin biopsy sections were incubated with an IgG anti-tissue transglutaminase mouse monoclonal antibody. After washing, sections were incubated with anti-mouse IgG. RESULTS: The anti-tissue transglutaminase monoclonal antibody specifically recognised the basal epidermal cells. This staining was no different between patients and controls. CONCLUSION: Our results suggest that tissue transglutaminase can be recognised in the basal epidermal layer both of patients with dermatitis herpetiformis and controls. Since this distribution does not correspond to the distribution of dermal IgA deposits, it is concluded that dermatitis herpetiformis dermal IgA deposits are not due to antibodies directed against cutaneous tissue transglutaminase.

Adult↗
PubMed2003

Gliadin and tissue transglutaminase complexes in normal and coeliac duodenal mucosa.

Tissue transglutaminase (tTG) seems to be the target self-antigen for endomysial antibodies in coeliac disease (CD) and to catalyse the critical deamidation of gliadin which strengthens its recognition by HLA-restricted gut-derived T cells. To date, it has not been demonstrated whether gliadin is cross-linked to tTG within the gut wall, a phenomenon known to occur in vitro. We therefore investigated the putative presence of tTG and gliadin complexes directly in duodenal mucosa. The immunoprecipitation and Western blotting experiments were performed on mucosal biopsies obtained from untreated, treated CD patients and biopsied controls, by using either anti-tTG or anti-gliadin antibodies, in both denaturating/reducing or nondenaturating/nonreducing conditions. A subset of experiments was performed by using anti-tTG antibodies purified by affinity chromatography from sera of untreated coeliac patients. The localization of tTG and gliadin was studied by immunofluorescence at confocal laser microscopy on seriate sections of diseased and normal duodenal mucosa by using the same antibodies of the coimmunoprecipitation section. The amounts of tTG and gliadin coimmunoprecipitated with anti-tTG monoclonal antibody in untreated CD mucosa were significantly increased compared to those of the other two groups. When performing the experiments in nondenaturating/nonreducing conditions, a high molecular weight band formed by both molecules, was evidenciated. Also the anti-tTG antibodies purified from patients' sera turned out to be able to coimmunoprecipitate the two molecules. The analysis by confocal microscopy showed that tTG colocalizes with gliadin at the epithelial and subepithelial levels in active CD, and only in the lamina propria of the villi in normal mucosa. Our findings firstly demonstrated that gliadin was directly bound to tTG in duodenal mucosa of coeliacs and controls, and the ability of circulating tTG-autoantibodies to recognize and immunoprecipitate the tTG-gliadin complexes.

Adult↗
PubMed2003

Microvascular assessment in Behçet disease: videocapillaroscopic study.

The aim of this study was to evaluate microvascular assessment in patients with Behcet disease (BD) by means of an intravital videocapillaroscopic study. Sixteen BD patients were compared with an equivalent group of healthy subjects matched for age and sex. Videocapillaroscopy (VCP) was performed in peripheral areas and in conjunctiva, and morphological and quantitative parameters were assessed. In both areas VCP showed several morphological alterations (microaneurysms, megacapillaries, desertification areas) detectable in a high percentage of patients; quantitatively we found significant changes of incisuring and sludging score, of capillary loop intermediate branch length (in peripheral areas) and of arteriole/venule diameter (in conjunctiva). Therefore, vessel involvement included both the number and the whole vessel structure and was seen both in peripheral and conjunctival areas when the two different vascular beds of micro- and paramicrocirculation were examined. We conclude that an important rearrangement of microcirculation is detectable in BD and that VCP may have diagnostic and prognostic value, providing qualitative and quantitative information able to define the systemic extension of vascular damage and the degree of vessel wall alteration.

Adult↗
PubMed2002

Coeliac disease.

In the last few decades, the comprehension of epidemiological, pathogenic and clinical aspects of coeliac disease has increasingly improved. Serological screening studies on the general population have shown that the true coeliac disease prevalence in Europe is higher than previously reported. It has become clear that tissue transglutaminase has a crucial role in the pathogenesis of coeliac disease pathogenesis, and there is evidence that substitution of deamidated amino acidic residues at a critical position along the gliadin sequence dramatically increases immunological activation. The toxicity of many gluten epitopes has been investigated, so far, but recent studies have indicated the region 57-75 of alpha gliadin as a possible candidate epitope in the pathogenesis of coeliac disease. However, the wide heterogeneity of gliadin and glutenin molecules complicate any attempts to identify the toxic epitope, and the fascinating idea to produce detoxified grains will represent a great challenge in the near future. From a clinical point of view, there is now evidence of a broad spectrum of gluten conditions. Extra-intestinal signs, i.e., alopecia, unexplained neurological disorders, cryptic hypertransaminasaemia, increased red cell width, frequently constitute the only clinical manifestation at the diagnosis.

Celiac Disease↗
PubMed2002

Clinical features of coeliac disease.

Aim of this review is to describe the extremely variable clinical presentation of coeliac disease. Moreover due to these varying manifestations, "coeliac literature" is characterised by a very rich terminology, which has not been unified, so far To help readers, not familiar with that terminology, we have given an explanation for the most common coeliac terms.

Celiac Disease↗
PubMed2001

Intestinal permeability in Crohn's disease patients and their first degree relatives.

BACKGROUND: Family studies suggested that an altered intestinal permeability plays a role in the genesis of Crohn's disease. AIM: Aim of the present study was to investigate a possible genetic alteration of the mucosal barrier in Crohn's disease. SUBJECTS: 16 Crohn's disease patients and 26 of their cohabiting first degree relatives were studied. METHODS: To investigate intestinal permeability, Cellobiose/Mannitol test was administered to both groups. RESULTS: In the two groups, we found that the median intestinal permeability values were higher and statistically different from those obtained in 32 healthy control subjects as well as in five healthy control families. Six (37.5%) Crohn's disease patients and three (11.5%) of their first degree relatives showed increased individual intestinal permeability values. Intestinal permeability alteration in Crohn's disease patients was unrelated to sex, age, disease activity, localisation, duration, treatment schedule, as well as to serum anti-Saccharomyces cervisiae antibody positivity in a pilot study conducted in 7 Crohn's disease patients; anti-Saccharomyces cervisiae antibody values were negative in all 10 first degree relatives investigated. CONCLUSIONS: These findings demonstrate the increase in IP in 37% of the patients and in 11% of their relatives. More extensive investigation of the correlation between ASCA alterations and IP will be needed in both patients with Crohn's disease and their relatives.

Adult↗
PubMed2001

Endomysial and tissue transglutaminase antibodies in coeliac sera: a comparison not influenced by previous serological testing.

BACKGROUND: Since transglutaminase was shown to be the antigen of endomysial antibodies (EMA), it has become possible to screen for coeliac disease (CD) with an enzyme-linked immunosorbent assay (ELISA) for transglutaminase antibodies (TTA). However, it is possible that sera used to show that TTA are found in CD were obtained from patients diagnosed because they were positive for EMA. So, a comparison between EMA and TTA has not been possible so far. METHODS: EMA and TTA were tested in sera from 52 controls and 56 untreated CD patients, who had not undergone serological testing. Samples were tested for TTA with an ELISA kit. Based on the ROC analysis of a pilot study, results were considered as either positive, borderline, or negative. EMA were analysed by indirect immunofluorescence on monkey oesophagus. RESULTS: Forty-nine CD patients were positive for TTA, six borderline, one negative. Forty-four controls were negative, seven borderline, one positive. If we consider borderline results to be positive, sensitivity is 98.2% and specificity 84.6%. EMA were positive in 53 CD patients; the controls were all negative. Performing TTA in all cases and EMA only in the few TTA borderline cases (12.0%) would have a sensitivity of 94.6% and a specificity of 98.1%. CONCLUSIONS: This study is the first to compare TTA with EMA. Due to 100% specificity and high sensitivity, EMA seems to be the most accurate coeliac antibody. Conversely, TTA offer advantages in terms of sensitivity and simplicity. A satisfactory strategy is to use TTA first and then EMA to confirm the borderline results.

Adult↗
PubMed2001

Defining gluten refractory enteropathy.

OBJECTIVE: The diagnosis of coeliac disease (CD) is based on the responsiveness of the enteropathy to a gluten-free diet (GFD). This implies that terms such as 'non-responsive CD' and 'refractory CD' are almost paradoxical. In spite of this, these terms are commonly used in the literature, often with different and confusing meanings. METHODS: On the basis of both a review of the literature and our clinical experience, we propose the following classification. A condition characterized by a refractory enteropathy, not due to lymphoma, ulcerative jejunoileitis or collagenous sprue, but in which gluten sensitivity has been shown previously or could be shown while the patients were on an immunosuppressive therapy should be indicated as refractory CD. Those patients in whom gluten sensitivity can be excluded should be considered to be affected by non-coeliac refractory sprue. Finally, patients in whom the presence of CD cannot be either confirmed or excluded should be considered to be affected by undefined sprue. RESULTS: Twenty-four certain refractory patients are described in the literature. The data suggest a diagnosis of refractory CD in 13 patients, non-coeliac refractory sprue in three patients, and undefined sprue in eight patients. CONCLUSIONS: We define refractory CD as a form of CD that no longer responds to a GFD. Non-coeliac refractory sprue is a condition unrelated to CD. It could be either an independent condition or a common end point of different enteropathies.

Adult↗
PubMed2000

Coeliac disease and Down syndrome: associations not due to genetic linkage on chromosome 21.

BACKGROUND: Individuals with Down syndrome have an increased prevalence of coeliac disease (CD). The HLA region accounts for only 30% of the heritability of CD, and segregation analyses have suggested the involvement of at least one other non-HLA gene. Distribution of known HLA susceptibility types in Down syndrome and normal populations are similar and do not explain the difference in disease frequency. This study tests the hypothesis that the association between these disorders is due to a susceptibility gene for coeliac disease being present on chromosome 21. METHODS: We studied 21 families multiply affected with CD, none of whom had Down syndrome. The typing information of six microsatellite markers across chromosome 21 was used to test linkage. RESULTS: Negative results from lod score and model-free linkage analysis were obtained, providing no support for genetic linkage of coeliac disease to chromosome 21 in this population. CONCLUSIONS: The high prevalence of coeliac disease in Down syndrome is not due to an increased copy number of a polymorphic susceptibility gene on chromosome 21.

Celiac Disease↗
PubMed2000

Endomysial antibody production is not related to histological damage after in vitro gluten challenge.

OBJECTIVE: To determine whether in vitro induction of endomysial antibodies is an in vitro marker of coeliac toxicity. DESIGN: To determine whether in vitro endomysial antibodies induced by gliadin incubation correlate with histological damage induced by in vitro gliadin challenge. METHODS: Small-bowel organ cultures from seven patients with treated coeliac disease were incubated in an organ culture system with gliadin; histological damage was morphometrically evaluated and endomysial antibodies were measured in the organ culture supernatant by indirect immunofluorescence. RESULTS: Although incubation with gliadin caused histological damage, there was no detectable production of endomysial antibody. CONCLUSIONS: In vitro, endomysial antibody induction cannot be used as a marker of coeliac toxicity. Endomysial antibodies are not necessary for generating the histological lesion of coeliac disease.

Adult↗
PubMed2000

Eosinophilic pleural effusion due to mesalamine. Report of a rare occurrence.

Mesalamine-induced lung toxicity has often been described. We report on a case of a patient who underwent mesalamine treatment, though in the absence of established criteria required for diagnosing Crohn's disease (CD) or ulcerative colitis (UC). He developed an adverse respiratory reaction to the drug, thus definitely proving its lung damaging capacity. The clinical presentation included eosinophilic pleural effusion, a feature never previously described in association with mesalamine intake.

Adult↗