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Biomedical subjects

M Bonamico

Publications and source records attributed to M Bonamico.

At least 19 recordsLinked to original sources
PubMed2006

Evidence of a selective epitope loss of anti-transglutaminase immunoreactivity in gluten-free diet celiac sera: a new tool to distinguish disease-specific immunoreactivities.

The aim of the present study was to evaluate the epitope specific humoral human tissue transglutaminase (tTG) immunoreactivity against 3 different human recombinant tTG constructs [(full-length tTG (a.a. 1-687), tTG (a.a. 227-687); tTG (a.a. 473-687)] before and after the introduction of a gluten-free diet (GFD). To this end, sera from 64 celiac disease (CD) subjects on a gluten-containing diet (44 f, 20 m) and after 0.6 +/- 0.3 years and 2.1 +/- 1.3 years of GFD were studied using a quantitative radioimmunoprecipitation assay. All 64 CD patients at diagnosis were full-length anti-tTG (a.a. 1-687)Ab positive. These Abs significantly decreased in frequency and titer after 6 months and 2 years of GFD. However, at low titers, 64.1% (41/64) of CD patients were still fl-tTG (a.a. 1-687)Ab positive after 2 years of GFD. At disease diagnosis, 70.3% (45/64) of the CD patients had Abs directed against fragments (227-687) and/or (473-687) of the tTG protein. This percentage, after 2 years of GFD, significantly decreased to 18.7%, whereas almost 50% of GFD patients had no tTG (227-687) and tTG (473-687) fragment reactivity, but only persistent, low-titer full-length tTG (1-687)Abs. We suggest that the selective loss of immunoreactivity against tTG (227-687) and tTG (473-687) fragments in CD patients with a GFD, could be due to quantitative decrease of autoreactivity driven by tTG-gliadin interaction underlying celiac disease pathogenesis.

Adolescent↗
PubMed2003

Body composition in coeliac disease adolescents on a gluten-free diet: a longitudinal study.

Our aim was to evaluate body composition in a group of coeliac disease adolescents on a gluten-free diet and to re-examine them at the end of the adolescence spurt. We studied 48 patients (group 1A), 30 age-matched healthy controls (group 2A), 11 group 1A patients after 4 years (group 1B) and 11 adolescents who were age- and sex-matched with group 1B (group 2B). Weight, height, bone mineral content, fat mass, fat-free mass (FFM) and bone mineral density were evaluated using dual-energy X-ray absorptiometry. All parameters were lower in group 1A than in group 2A subjects ( p<0.001). After 4 years, the body compartments of group 1B coeliac disease patients normalised, except for weight and FFM which remained lower than in group 2B subjects ( p<0.005). In conclusion, our study demonstrates that adolescence is a period where some parameters of body composition can still be recovered.

Absorptiometry, Photon↗
PubMed2003

Celiac disease-associated transglutaminase autoantibody target domains at diagnosis are age and sex dependent.

The contribution of age and/or sex to the transglutaminase (tTG) autoantibody response in celiac disease (CD) is not known. To gain insights into transglutaminase humoral autoimmunity at CD diagnosis, our aim was to characterize the autoimmune response against three tTG constructs [(full-length tTG(a.a.1-687), tTG(a.a.227-687), and tTG(a.a.473-687)] and to investigate into its relationship with CD patients' age and sex. One hundred seventy-five newly diagnosed CD patients (115 females and 60 males), subdivided into different groups according to age and sex, were studied using a serum 35S-radioimmunoassay. We found that among full-length tTG autoantibody-positive CD subjects (175/175), 50.9% (89/175) and 83.4% (146/175) had autoantibodies against tTG(227-687) and tTG(473-687) domains, respectively. Female patients of less than 4 years expressed tTG(227-687)Abs in significantly higher percentage and mean autoantibody titers vs. all other groups investigated, and tTG(473-687)Abs in significantly higher titers with respect to adult female patients. Our data identify a subset of CD patients showing a strong humoral tTG immunoreactivity at diagnosis, thus suggesting that age and sex influence the anti-tTG autoantibody response.

Adolescent↗
PubMed2001

Prevalence and clinical picture of celiac disease in italian down syndrome patients: a multicenter study.

BACKGROUND: A multicenter research study of Down syndrome patients was carried out to estimate the prevalence of celiac disease in patients with Down syndrome and to show clinical characteristics and laboratory data of Down syndrome patients. METHODS: The authors studied 1,202 Down syndrome patients. Fifty-five celiac disease patients (group 1) were compared with 55 immunoglobulin A antigliadin-positive antiendomysium antibodies-negative patients (group 2) and with 57 immunoglobulin A antigliadin-negative antiendomysium antibodies-negative patients (group 3). RESULTS: Celiac disease was diagnosed in 55 of 1,202 Down syndrome patients (4.6%). In group 1, weight and height percentiles were shifted to the left, whereas these parameters were normally distributed in groups 2 and 3. In celiac patients, diarrhea, vomiting, failure to thrive, anorexia, constipation, and abdominal distension were higher than in the other two groups. Low levels of hemoglobinemia, serum iron, and calcium were observed more frequently in group 1. The diagnosis of celiac disease was made after a mean period of 3.8 years from the initiation of symptoms. Sixty-nine percent of patients showed a classic presentation, 11% had atypical symptoms, and 20% had silent celiac disease. Autoimmune disorders were more frequent (30.9%) in group 1 than in the other two groups examined (15%; P < 0.05). CONCLUSIONS: This study reconfirms a high prevalence of celiac disease in Down syndrome. However, the diagnostic delay, the detection of atypical symptoms or silent form in one third of the cases, and the increased incidence of autoimmune disorders suggest the need for the screening of celiac disease in all Down syndrome patients.

Adolescent↗
PubMed2001

Radioimmunoassay to detect antitransglutaminase autoantibodies is the most sensitive and specific screening method for celiac disease.

OBJECTIVE: The aim of this study was to establish the most sensitive and specific screening method for celiac disease. We tested three methods based on different principles, which all detect autoantibodies against the same antigen (tissue transglutaminase). METHODS: Sixty-two celiac children at the first biopsy (group 1), 78 celiac children on a gluten-free diet (group 2), 14 celiac children on a gluten-challenge (group 3), and 56 controls with a normal duodenal mucosa (group 4) were studied. The methods used were: 1) radioimmunoprecipitation assay using recombinant tissue transglutaminase (RIA); 2) commercial enzyme immunoassay using guinea pig tissue transglutaminase (ELISA); and 3) indirect immunofluorescence method for detection of antiendomysium antibodies (IF-EMA). RESULTS: RIA antitransglutaminase autoantibodies were detected in 100% of group 1, 43.6% of group 2, 100% of group 3, and none of the control subjects. ELISA antitransglutaminase autoantibodies were detected in 90.3% of group 1, 9% of group 2, 78.6% of group 3, and in none of the control subjects. IF-EMA were detected in 95.2% of group 1, 11.5% of group 2, 92.3% of group 3, and 1.8% of the controls. CONCLUSIONS: Our results demonstrate a very high sensitivity and specificity of the RIA method to detect antitransglutaminase autoantibodies in comparison to ELISA and IF-EMA assays. We can explain this finding with the use of human recombinant antigen and the increased capacity of the RIA method to detect low titers of autoantibodies. If our data are confirmed by studies on larger series, tissue transglutaminase RIA could be proposed as the best screening method for celiac patients.

Adolescent↗
PubMed2001

Usefulness of endoscopic small intestinal biopsies in children with coeliac disease.

Small intestinal biopsy is the most important diagnostic method in the routine evaluation of children with chronic diarrhoea and malabsorption. At present morphological alterations are considered essential in the diagnosis of coeliac disease (CD) and the presence of a normal small bowel biopsy specimen, observed in patients eating a diet containing gluten, rules out the diagnosis of CD. The small intestinal biopsy can be carried out either by blind suction capsule or by endoscopic forceps. In everyday clinical practice endoscopic duodenal biopsies, if taken and handled suitably, are accepted as equivalent to capsule biopsies from the proximal jejunum. In the study we reported some patients in whom has been possible to demonstrate the presence of total villous atrophy in one biopsy, while other duodenal samples taken in different duodenal portions were normal or showed mild lymphocytes and plasmacells infiltrations of the lamina propria. In patients with this type of biopsy pathology, wherein flat mucosa has been found even close to normal mucosa, the possible explanation is mucosal patchiness. The occurrence of patchly distributed intestinal atrophy in children suffering of CD raises the question of the validity of using the peroral capsule, widely believed to be the best standard for the diagnosis of CD. In our opinion, small intestinal biopsies obtained via endoscopy are more reliable than the peroral capsule biopsies in order to identify patchy mucosal atrophy and could be very useful for a correct diagnosis in CD patients.

Adolescent↗
PubMed2000

Importance of gluten in the induction of endocrine autoantibodies and organ dysfunction in adolescent celiac patients.

OBJECTIVE: It is well known that a high number of celiac patients may develop autoantibodies against endocrine glands, but it has not yet been clarified if this increased autoimmune response and the impaired organ function that can develop may be related to the presence or absence of gluten in the diet. The aim of the present study was to evaluate the effect of gluten on the autoimmunity and function of the endocrine glands in adolescent celiac patients. METHODS: To clarify this aspect we investigated 44 patients (28 females), aged 11-20 yr (15.21+/-2.7 yr): 25 (mean age, 15.1+/-2.2 yr) on a gluten-free diet (treated patients) and 19 (mean age 15.4+/-2.9 yr) with a diet containing gluten (untreated patients). Forty adolescent subjects, aged 14-19 yr (mean age, 14.9+/-2.7 yr), of whom 20 were females, were studied as controls. Antibodies against the thyroid, adrenal, and pancreas were evaluated. Thyroid-stimulating hormone FT3, FT4, T3, T4, dehydroepiandrosterone sulphate, 17-OH progesterone, and cortisol, analyzed basally and 60 min after intravenous ACTH stimulation, were assayed to evaluate thyroid and adrenal function. The fasting glycemia level was used to evaluate the endocrine pancreas function. An ultrasonogram of the thyroid gland was performed on all patients. HLA class II typing for DR3 and DQB1 was performed in 32 of 44 patients. RESULTS: Seven of 44 (15.9%) patients were positive for antibodies against peroxidase. Six of 44 (13.6%) were positive for antibodies against thyreoglobulin and four of them also showed positive antibodies against peroxidase. Therefore, in nine of 44 at least one antibody directed against thyroid tissue was positive. Seven of 44 (15.9%) were positive for antibodies against islet cell, one of 44 (2.3%) positive for antibodies against glutamic acid decarboxilase, one of 44 (2.3%) positive for antibodies against insulin, and none for antibodies against islet cell- 512bdc. In 15 of 44 (34%) at least one antibody against an endocrine tissue was positive. The genotype DR3 was found in 21 of 32 (65.6%) celiac patients (10 in the untreated and 11 in the treated group, respectively) and the genotype DQB1*02 (DQ2) was found in 30 of 32 (93.8%) patients (16 in the treated and 14 in the untreated group, respectively). DHA-S values were significantly lower in the untreated (30.5+/-28.5 microg/dl) than in the treated group (61.3+/-59.4 microg/dl, p < 0.05), and both showing significantly (p < 0.01) lower levels with respect to the controls (161+/-52 microg/dl). One patient showed diabetes, another one clinical hypothyroidism (thyroid-stimulating hormone > 6), and two patients showed preclinical hypothyroidism. Interestingly, at least one antibody was positive in 10 of 19 untreated patients (52.6%) but only in five of 25 treated patients (20%), with a significantly different distribution (p < 0.001) between the two groups and without differences in the HLA genotype. The ultrasonographic evaluation of the thyroid resulted in a pathological score in six patients of the 44 examined (13.6%), suggesting the presence of thyropathy. CONCLUSIONS: The main results of this study are the high incidence of thyroid and pancreatic antibodies, and the possible role of gluten in the induction of the antibodies as well as, in few cases, the consequent organ dysfunction.

Adolescent↗
PubMed1999

Assessment of body composition by bioelectrical impedance in adolescent patients with celiac disease.

OBJECTIVE: Assessment of body composition is of primary importance in the management of celiac adolescents. We aimed to evaluate body composition by dual-energy x-ray absorptiometry and bioelectrical impedance in celiac adolescents on a gluten-free diet to investigate whether impedance may provide an alternative method to assess nutritional status in these patients. METHODS: We studied body composition in 43 adolescents affected by celiac disease on a gluten-free diet for > or = 1 yr and 30 healthy subjects. Fat, fat-free, and bone masses were assessed by dual-energy x-ray absorptiometry. Fat and fat-free masses were also assessed by bioelectrical impedance. All anthropometric measurements were performed according to standard procedures. RESULTS: All patients had a significantly lower body weight, height, fat-free mass, bone mineral density (p < 0.001), and body mass index (p < 0.01) compared with controls. In contrast, parameters predicting fat compartment (sum of skinfolds and fat mass) did not differ from those of controls. No significant difference was found between patients strictly adherent to a gluten-free diet and patients partially compliant. Compared with dual-energy x-ray absorptiometry measurements, bioelectrical impedance showed a high accuracy to estimate fat-free mass (R2 = 0.97) and limited accuracy for fat mass (R2 = 0.75). Furthermore, impedance was more reliable for estimating hydration of soft tissue underlying the fat-free mass changes. CONCLUSIONS: In adolescents with celiac disease, after a mean of 1 yr of gluten-free diet all the parameters assessing body compartments, except fat mass, were affected, compared with healthy controls. Bioelectrical impedance holds promise for routine assessment of body composition changes in celiac adolescents on a gluten-free diet.

Absorptiometry, Photon↗
PubMed1998

Celiac disease and Turner syndrome.

BACKGROUND: Short stature is one of the features of Turner syndrome and a form of presentation of monosymptomatic celiac disease. METHODS: The recognition of celiac disease in two antiendomysium antibody-positive Turner syndrome girls who did not respond to growth hormone treatment led us to perform as a screening for celiac disease IgA and IgG antigliadin antibodies and antiendomysium antibodies determination in other 35 Turner syndrome patients. Intestinal biopsy was proposed to the antiendomysium antibodies-positive girls; in the former, subtotal villous atrophy was found; in the latter, one parent's consent for intestinal biopsy was not obtained. RESULTS: The prevalence of celiac disease in Turner syndrome patients observed in the present study (8.1 if we consider 3 villous atrophy, 10.8 if we consider 4 antiendomysium antibody-positive) is quite high and seems to indicate that the association of these two disorders could not be coincidental. As to the clinical picture, celiac disease appeared atypical in one case, typical in another one and as a silent form in the third case. Of the 3 cases with villous atrophy on gluten-free diet growth hormone therapy was not effective in two girls, who were older than 16 years, while in the younger patient, detected by the screening, a significant increment of height velocity and height Standard Deviation Score for Chronological Age according to Turner references was observed. CONCLUSIONS: This study suggests that celiac disease can be associated with Turner syndrome and even responsible for a failure of growth hormone therapy. Therefore we propose to perform in Turner syndrome patients antiendomysium antibody determination as a screening followed by intestinal biopsy in positive cases. This would be advisable at least before starting growth hormone treatment.

Adolescent↗
PubMed1998

The gluten-free diet: a nutritional risk factor for adolescents with celiac disease?

BACKGROUND: The gluten-free diet is the standard therapy for patients affected by celiac disease, although compliance with the diet is not optimal in adolescents or adults. Moreover, the gluten-free diet may induce nutritional imbalances. METHODS: Alimentary habits and diet composition were examined in 47 adolescents with celiac disease and 47 healthy aged-matched control subjects. All subjects compiled a 3-day alimentary record that allowed determination of their energy intakes: the macronutrient composition of their diets; and their iron, calcium, and fiber intakes. To evaluate compliance with the gluten-free diet, immunoglobulin A antigliadin and antiendomysium antibodies were assessed in all with celiac disease. RESULTS: The analysis of the records and the results of antibody levels showed that 25 subjects strictly followed dietetic prescriptions (group 1A), whereas 22 patients consumed gluten-containing food (group 1B). Those with celiac disease and control subjects (group 2) consumed a normocaloric diet. Lipid and protein consumption was high, however, and the consumption of carbohydrates low. Moreover, dietary levels of calcium, fiber, and especially in girls, iron, were low. These nutritional imbalances were significantly more evident in group 1A than in group 1B, as a consequence of poor alimentary choices. Moreover, in group 1A overweight and obesity were more frequent (72%) than in group 1B (51%) and in the control subjects (47%). CONCLUSIONS: In people with celiac disease, adherence to a strict gluten-free diet worsens the already nutritionally unbalanced diet of adolescents, increasing elevated protein and lipid consumption. In the follow-up of patients with celiac disease, considerable effort has yet to be made to improve compliance with a gluten-free diet, and especially to control the nutritional balance of the diet in compliant patients.

Adolescent↗
PubMed1997

Screening for coeliac disease: the meaning of low titers of anti-gliadin antibodies (AGA) in non-coeliac children.

Coeliac disease is diagnosed by means of jejunal biopsy, an invasive procedure. Anti-gliadin antibodies (AGA) have therefore been used in the first screening of the disease. On the other hand, low titers of AGA are widely detected also in normal subjects. In order to investigate if low levels of AGA could be correlated with laboratory and clinical data, we performed a study on 167 subjects with various illnesses, such as recurrent abdominal pain, failure to thrive, short stature, diarrhoea or constipation, cow-milk protein intolerance and/or food allergy, recurrent vomiting or previous gastroenteritis, all non coeliac conditions which have been associated with AGA presence. Seventy coeliac children, all biopsied, were selected as a control group. Among the 167 cases we found 60 subjects positive for AGA (35.9%), a high proportion as compared with the general population. Only 33/167 patients, all IgG and IgA AGA positive, fulfil our laboratory and clinical criteria to perform a 'confirming' biopsy. For the 134 residual cases (14 IgA, 13 only IgG AGA positive, 107 AGA negative) a diagnosis of coeliac disease has been excluded by clinical criteria (scoring). As a whole, the patients with coeliac disease had significantly higher levels of AGA of both IgG and IgA classes (p < 0.01). On the other hand, no significant difference emerged for all the anamnestic and laboratory parameters considered between AGA+ and AGA- non-coeliac subjects. However, laboratory parameters of IgG-AGA and/or IgA-AGA positive patients were similar to those of coeliac children for ion, Xylose, total IgA count. As no biopsied case showed mucosal atrophy, it is suggested that the presence of even low AGA levels in non-coeliac children may represent a highly sensitive index of intestinal alteration causing an increased permeability to macromolecules, but it is very unlikely that one could detect coeliac children by means of Ig-AGA among such illnesses and normal subjects. Strong clinical diagnosis and laboratory parameters are required to justify intestinal biopsies. In fact, the production of AGA seems to be a merely immunological phenomenon linked to an increased and probably transient permeability to macromolecules of the intestinal mucosa.

Adolescent↗
PubMed1997

Genetic contribution of the HLA region to the familial clustering of coeliac disease.

In order to assess the effect of the HLA region on familiality of coeliac disease (CD), we carried out a study on 121 CD index cases and 325 first degree relatives. The transmission disequilibrium test confirmed the importance of the HLA-DR3 haplotype in CD susceptibility. However, the different distortion found in affected children inheriting maternal or paternal DR3 alleles suggested that the sex of the parent might influence the risk conferred by this haplotype. The increase in risk to siblings of affected individuals relative to the risk in the general population (lambda s) and the contribution of the HLA genes to this clustering (lambda sHLA) have also been estimated. Non-overlapping data from the literature have been collected and combined with our sample to extend such analysis. Then, the percentage contribution of the HLA region to the development of CD among siblings was 36.2%. This result confirms that the HLA genotypes are an important genetic background to CD development but shows that additional susceptibility factors remain to be identified.

Celiac Disease↗
PubMed1997

Helicobacter pylori duodenal colonization in children.

To investigate the prevalence and the significance of Helicobacter pylori duodenal colonization, endoscopic duodenal biopsies were performed in 168 children with chronic abdominal pain, gastroesophageal reflux, gastrointestinal bleeding, and malabsorption syndrome. Helicobacter pylori infection was detected in 68 children (40.4%): in 31 of them H. pylori was present in the gastric antrum, and in 37 in the duodenum also. Duodenitis was observed in 25 children with duodenal H. pylori; gastric metaplasia in 3. Scanning electron microscopy revealed the presence of the micro-organism in 3/13 cases; the bacteria were located in the intercellular spaces and alterations of the epithelial surface were found. In conclusion, H. pylori gastritis in children is often associated with duodenal colonization which can cause duodenitis, and also without gastric metaplasia, which indicates a possible role of the micro-organism in the pathogenesis of the lesions.

Adolescent↗
PubMed1996

Detection of a vacuolating cytotoxin in stools from children with diarrhea.

A cytotoxin inducing vacuolation in HEp-2 cells was detected in 19 (3.1%) of 618 stool specimens from children with diarrhea but in none of 135 from control children. Common enteric pathogens were found in only two (10.5%) of the 19 cytotoxin-positive stool specimens. The vacuoles induced by stool filtrates resembled those induced by the vacuolating toxin (VacA) of Helicobacter pylori. The vacuolating toxin was heat-labile and protease-sensitive, and it had an apparent molecular weight of > 100,000 but was not neutralized by an antiserum to H. pylori VacA. Although proper prospective case-control studies are needed to definitely assess the etiologic association between the new vacuolating cytotoxin and diarrhea, the present study suggests that microorganisms of the gastrointestinal tract produce a Helicobacter-like vacuolating toxin and may be responsible for cases of childhood diarrhea whose etiology is currently considered unknown.

Bacterial Proteins↗
PubMed1996

Frequency and clinical pattern of celiac disease among siblings of celiac children.

To investigate the prevalence and clinical and genetic patterns of celiac disease (CD) among siblings of CD patients, 103 siblings and one twin of 80 celiac children were evaluated by means of their clinical history, physical examination, blood indices of nutritional status, and antigliadin antibodies (AGA). Antiendomysium antibody (AEA) levels were determined in 70 patients and 85 subjects were human leucocyte antigen (HLA) typed. On the basis of clinical or laboratory data or both, 21 siblings (20.2%) were submitted to intestinal biopsy, whereas intestinal biopsy in six siblings with positive serologic screening (AGA IgA or AEA or both) was not performed because of parental refusal. In a high percentage of cases (18%), all on a gluten-containing diet, the intestinal mucosa was atrophic, and CD was subsequently diagnosed. Because we could not submit all the siblings to intestinal biopsy, this figure could underestimate the real prevalence of the disease in our series; consequently, it was not possible to calculate accurately the sensitivity and specificity of AGA and AEA. Nevertheless, AEA (positive in all the nine siblings with mucosal atrophy), followed by AGA IgA, proved to be the best screening for CD. Eighteen of 19 CD siblings showed HLA-predisposing antigens. Among the 19 CD siblings, one showed a typical form with gastrointestinal symptoms, two had short stature, one suffered from recurrent vomiting, and in 15, the disease was clinically silent. On the contrary, among siblings who were first diagnosed (index cases), the majority (73.7%) had a typical form of CD, and no clinically silent cases were observed. We did not find any difference between index cases and CD siblings in food habits and distribution of HLA antigens. In 15 of 18 cases, the sibling diagnosed subsequently was the older one. Finally, the typical form of CD was significantly more frequent among the younger brother than the older. In conclusion, the high prevalence of the silent form of CD in our cases indicates that siblings of CD subjects should always be screened for CD. The combination of AGA IgA and AEA represent a good screening method to use in selecting children for the intestinal biopsy.

Celiac Disease↗
PubMed1996

Down syndrome and coeliac disease: usefulness of antigliadin and antiendomysium antibodies.

The usefulness of antigliadin (AGA) and antiendomysium antibodies (EMA) as a screening test for coeliac disease (CD) in 113 Down syndrome (DS) patients (61 children) was evaluated. AGA IgA were present in 22.1%, AGA IgG in 48.6%, EMA in 6.2%. Four symptomatic patients, AGA- and EMA-positive, were affected by CD (3.5%). In three AGA-positive and EMA-positive subjects, permission for intestinal biopsy was refused, while in two AGA-positive and EMA-negative children, the intestinal mucosa was normal. Our study confirms the association of CD and DS, and suggests the usefulness of EMA determination as a test for selecting DS patients for intestinal biopsy.

Adolescent↗