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Biomedical subjects

R Troncone

Publications and source records attributed to R Troncone.

At least 55 records · Page 3Linked to original sources
PubMed1998

Celiac disease: a reappraisal.

During the last decade significant changes have occurred in our concepts of celiac disease. As a result of the implementation of sensitive and specific serologic tests, the epidemiology and clinical presentation of affected patients have been radically reconsidered. Extraintestinal manifestations of celiac disease have been radically reconsidered. Extraintestinal manifestations of celiac disease have been increasingly recognized, and the strict association with diseases recognized as autoimmune disorders is well established; celiac disease itself has many aspects of an autoimmune condition. Celiac disease is of interest to clinicians and scientists because it represents a valuable model for the comprehension of diseases in which environmental, genetic, and immunologic factors interplay.

Celiac Disease↗
PubMed1998

Majority of gliadin-specific T-cell clones from celiac small intestinal mucosa produce interferon-gamma and interleukin-4.

An abnormal mucosal cell-mediated immune response plays a fundamental role in the pathogenesis of celiac disease. To characterize locally infiltrating T cells, gliadin-specific T-cell clones were isolated from two treated celiac patients. Mucosal biopsies were cultured in vitro for 24 hr with a peptic-tryptic digest (PT) of gliadin. T-cell clones (TCC) were then isolated by limiting dilution. The production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was evaluated by ELISA in culture supernatants obtained after a short incubation with anti-CD3 and PMA, or with antigen. Twenty-two TCC were specific for gliadin and/or PT. All were CD3+, CD4+, CD8-, TCR alphabeta+. In one such clone the PT-specific response was inhibited by an anti-DQ, but not by an anti-DR antibody. Of the five gliadin-specific TCC examined, four produced IL-4 and high levels of IFN-gamma; the remaining one initially produced only IL-4, but subsequently also IFN-gamma. All clones obtained from the celiac mucosa, including the gliadin-specific ones, produced high levels of IFN-gamma, in most cases with IL-4. This cytokine profile could explain most of the immunological features of the celiac mucosa.

Adolescent↗
PubMed1998

Genome search in celiac disease.

Celiac disease (CD), a malabsorption disorder of the small intestine, results from ingestion of gluten. The HLA risk factors involved in CD are well known but do not explain the entire genetic susceptibility. To determine the localization of other genetic risk factors, a systematic screening of the genome has been undertaken. The typing information of 281 markers on 110 affected sib pairs and their parents was used to test linkage. Systematic linkage analysis was first performed on 39 pairs in which both sibs had a symptomatic form of CD. Replication of the regions of interest was then carried out on 71 pairs in which one sib had a symptomatic form and the other a silent form of CD. In addition to the HLA loci, our study suggests that a risk factor in 5qter is involved in both forms of CD (symptomatic and silent). Furthermore, a factor on 11qter possibly differentiates the two forms. In contrast, none of the regions recently published was confirmed by the present screening.

Celiac Disease↗
PubMed1998

Lack of correlation between genotype and phenotype in celiac disease.

BACKGROUND: Celiac disease has a wide range of clinical features. The goal of this study was to evaluate whether specific HLA genotypes are associated with particular clinical appearances. METHODS: One hundred forty-five patients with confirmed celiac disease were oligotyped for DR and DQ HLA genes. Clinical notes, physical examination, and a questionnaire provided their personal data. Patients were grouped into nine genotypic categories, according to the presence of the specific DQ heterodimer DQA1*0501-DQB1*0201 (hence termed alpha0beta0), in single or double dose, and the presence of the DRB4 antigen. RESULTS: Age at first symptoms and age at beginning of gluten-free diet were not significantly different in the nine groups. The initial symptoms of the disease had a similar distribution in all groups. In twenty-seven patients, disease was diagnosed by family screening: they shared a similar HLA genotype with those who had relevant symptoms. The actual growth status-evaluated by standardized height, percentage of median weight for age, and percentage of median weight for height--was not different in the nine groups. Presence of unusual health complaints was not associated with a specific genotype. CONCLUSIONS: There is no evidence that clinical features of celiac disease are associated with different HLA genotypes. Genes outside the HLA may play a relevant role.

Body Height↗
PubMed1998

Gliadin activates mucosal cell mediated immunity in cultured rectal mucosa from coeliac patients and a subset of their siblings.

BACKGROUND: CD3 and gamma delta cells in the rectal mucosa increase after local instillation of gluten in children with coeliac disease and in half of their siblings. Aim- To establish an in vitro system for assessing immunological changes induced by gluten in the rectum. PATIENTS AND METHODS: Rectal biopsy specimens obtained from 13 treated coeliac children, nine of their siblings, and nine controls were cultured in vitro with a peptic-tryptic digest of gliadin or ovalbumin. CD3 and CD25 cells were counted, and the expression of adhesion molecules evaluated. RESULTS: In the lamina propria of coeliac biopsy samples cultured with gliadin, but not in those from controls, the expression of vascular cell adhesion molecule 1 (VCAM-1) was enhanced, and the number of CD25 cells was significantly higher than in those cultured in medium alone; the density of intraepithelial CD3 cells was also significantly higher. No differences were noted in coeliac biopsy specimens cultured with ovalbumin. A discriminant analysis allowed correct classification of all controls and all coeliacs but one, but three of nine siblings were allocated to the coeliac group. CONCLUSIONS: Our data confirm that gliadin is able to activate cell mediated immunity in the rectal mucosa in coeliac patients and in a subset of their first degree relatives.

Adolescent↗
PubMed1997

Identical T-cell receptor beta chain rearrangements are present in T cells infiltrating the jejunal mucosa of untreated celiac patients.

The intestinal mucosal lesion in celiac disease is characterized by a predominant T-cell infiltration of both epithelium and lamina propria. However, a restricted use of T-cell receptors (TCR) in T lymphocytes infiltrating the jejunal mucosa of celiac patients has not been reported. Based on an immunohistochemical survey of jejunal biopsies from a cohort of untreated celiac patients, we demonstrated a small but significant increase of V beta 8.1/2+ T cells in the lamina propria, but not in the epithelium nor in the peripheral blood. Sequence analysis indicated the existence of a variable degree of clonality of V beta 8+ T cells in the celiac mucosa. More importantly, the recurrence of identical CDR3 regions in some patients was also observed. The altered distribution of V beta 8+ T cells and the presence of identical CDR3 regions in celiac patients, but not in controls was independently confirmed by CDR3 size analysis in a further cohort of patients. These findings suggest that disease-specific variations of the TCRBV8 repertoire are present in the small intestinal mucosa of untreated celiac patients.

Amino Acid Sequence↗
PubMed1997

Gut lavage IgG and interleukin 1 receptor antagonist:interleukin 1 beta ratio as markers of intestinal inflammation in children with inflammatory bowel disease.

BACKGROUND: Whole gut lavage is currently used as preparation before radiological or endoscopic examination of the large bowel. AIM: To validate the gut lavage technique for the assessment of mucosal inflammation, by measuring intestinal IgG and interleukin 1 beta (IL-1 beta) in the fluid obtained. PATIENTS: Sixteen children with Crohn's disease (CD), 14 with ulcerative colitis (UC), and 22 age matched controls. METHODS: Isotonic, non-absorbable polyethylene glycol based lavage solution was given orally or by nasogastric tube. Clear fluid was collected, filtered, and treated with protease inhibitors. IgG, IL-1 beta and IL-1-receptor antagonist (IL-1-ra) were measured by sandwich enzyme linked immunosorbent assay (ELISA). RESULTS: In patients with UC and CD, IgG and IL-1 beta levels were significantly (p < 0.001) higher than in controls. A positive correlation (p < 0.05) was found with disease activity scores. IL-1-ra levels were not significantly different in UC and CD, when compared with controls, but the IL-1-ra:IL-1 beta ratio was significantly (p < 0.01) lower in patients with UC and CD, and negatively (p < 0.001) correlated with IgG levels in lavage fluid. CONCLUSIONS: Gut lavage fluid IgG and IL-1 beta levels and IL-1-ra:IL-1 beta ratio may provide objective discrimination between active and inactive disease in children with inflammatory bowel disease.

Adolescent↗
PubMed1997

Compliance to a gluten-free diet in adolescents, or "what do 300 coeliac adolescents eat every day?".

BACKGROUND/AIMS: Compliance to a gluten-free diet is currently an important issue in the care of both adolescent and adult coeliac patients. The aim of this study was evaluate the compliance to a gluten-free diet and the dietary habits in general of coeliac teenagers and young adults. PATIENTS AND METHODS: A total of 306 adolescents and young adults were followed in a coeliac clinic. They were grouped on the basis of: strict compliance to a gluten-free dietary regimen (n = 223, 73%); dietary transgressions 2-3 times/month (n = 46, 15%); and frequent transgressions or a full gluten-containing diet (n = 37, 12%). RESULTS: The physical growth status was optimal in the male patients, and less so in the females, but was not related to compliance. Symptoms were very rare in all groups. Compliance to the diet was related to sex (females better than males), age (younger better than older), good school grades, and good self-esteem. CONCLUSIONS: The teen-agers studied consumed an average of about 11.32 kg/month of gluten-free products provided by the Italian Health System. Gluten-free pasta and bread were the daily choices. The mean cost for each patient was estimated to be Italian Lire 242,640 (ECU 124) per month or ECU 1,490/year.

Adolescent↗
PubMed1996

Gluten-sensitive enteropathy.

Gluten-sensitive enteropathy is induced by dietary wheat gliadin and related proteins in genetically susceptible individuals. Most evidence suggests that the mucosal lesion represents an immunologically mediated injury triggered by gluten in the context of a particular assortment of major histocompatibility complex genes. The amino acid residues of gliadin and related proteins responsible for toxicity have not been identified; in vitro systems are available, but definitive conclusions must rely on in vivo jejunal challenges. At a conservative estimate, symptomatic gluten-sensitive enteropathy affects approximately 1 in 1000 individuals in Europe; however, it is now becoming clear that a greater proportion of individuals has clinically silent disease, and probably many others have a minor form of the the enteropathy. In most countries, the clinical presentation has changed over the past few years coming closer to the adult type of the disease, and the age of onset of symptoms is shifting upward. Liver, joint, hematologic, dental, and neurologic symptoms are increasingly being recognized. Several diseases are associated the gluten-sensitive enteropathy, such as IgA deficiency, insulin-dependent diabetes mellitus, and a range of other autoimmune diseases. Tests based on the measurement of antigliadin and antiendomysium antibodies have gained success as noninvasive screening tests; however, the ultimate diagnosis still is based on the finding of a severe histologic lesion of the jejunum while the patient is on a gluten-containing diet and on its disappearance once the gluten is excluded from the diet. A lifelong, strict GFD is mandatory for celiac children. Among other long-term problems, an increased risk of intestinal lymphoma has been reported in patients on a normal gluten-containing diet.

Adult↗
PubMed1996

In siblings of celiac children, rectal gluten challenge reveals gluten sensitization not restricted to celiac HLA.

BACKGROUND & AIMS: Inflammatory changes in the rectum of patients with celiac disease after local instillation of gluten have been reported. The aim of this study was to examine rectal mucosa after local gluten challenge in children with celiac disease and their siblings. METHODS: Rectal biopsy specimens were obtained before and 6 hours after rectal challenge with a peptictryptic digest of gliadin in 33 children with treated celiac disease, 12 controls, and 19 siblings of children with celiac disease. Epithelium and lamina propria volumes were determined, and CD3+ and gamma delta + lymphocytes were counted. RESULTS: After local instillation of gliadin, a significant increment in the absolute number of intraepithelial lymphocytes was noted in patients with celiac disease but not in controls. Immunohistochemical analysis showed a significant increase in CD3+ and gamma delta + cells, with the gamma delta/CD3 ratio remaining unchanged after challenge. A discriminant analysis allowed correct classification of 100% of patients with celiac disease and controls. The same analysis was used to classify 6 of 13 siblings as having celiac disease. The positivity was not associated with the presence of the heterodimer encoded by the DQA*0501 DQB1*0201 alleles in any of the siblings. CONCLUSIONS: All patients with celiac disease were identified by rectal gluten challenge. Approximately half of the siblings reacted to rectal instillation of gluten. The genetic background of such sensitization to gluten remains to be elucidated.

Adolescent↗
PubMed1996

Latent and potential coeliac disease.

Under the umbrella of coeliac disease (CD), or gluten-sensitive enteropathy, the concepts of silent, latent and potential CD have recently been introduced. While silent CD is marked by severe damage to the jejunal mucosa in the absence of clinical symptoms, both latent and potential CD are characterized by jejunal mucosa that would be reported as normal by most clinical pathologists in an individual on a gluten-containing diet. As opposed to potential coeliac patients, latent subjects sometimes in their life have had a flat jejunal biopsy which recovered on a gluten-free diet. Latent coeliac patients are often symptomatic; neither high titres of gliadin antibodies nor mucosal changes (including raised intraepithelial lymphocyte counts) are obligate features of latent CD, although the presence of elevated endomysial antibodies is probably the best predictor of progression towards villous atrophy. The term potential CD has been proposed for those subjects who do not have, and have never had, a jejunal biopsy consistent with overt CD, and yet have immunological abnormalities similar to those found in coeliac patients. Good markers of potential CD include the presence of serum endomysial antibodies, a high count of intraepithelial lymphocytes and subtle pathological alteration such as increased density of intraepithelial lymphocytes expressing gamma delta T cell receptor, signs of activated mucosal cell-mediated immunity, coeliac-like intestinal antibody pattern, and positive rectal gluten challenge.

Antibodies↗
PubMed1996

Defective 'gut processing' of gliadin in mice with graft-versus-host enteropathy.

The gut mucosa plays an important role in the induction of oral tolerance. Extending previous observations, we have here shown that serum containing gut-absorbed gliadin induces suppression of the specific systemic immune response in recipient mice parenterally immunized with gliadin. Graft-versus-host reaction (GvHR) has profound effects on the gut mucosa, representing a model of immune-mediated enteropathy. The aim of our work was to investigate the gut handling and processing of gliadin in mice with GvHR. Binding to enterocytes, passage through the epithelium, and ability of the epithelium to convert this antigen into a tolerogenic form were assessed in BDF1 mice weaned on gluten-free diet, 2 weeks after the induction of a semiallogeneic GvHR. Binding of gliadin peptide B3144 to enterocytes was similar in controls and GvHR mice. After feed, serum levels of gliadin were comparable in the two groups of mice, but when serum collected from GvHR mice and containing gut-absorbed gliadin was transferred intraperitoneally into naive recipient mice, this did not induce suppression of the specific immune response. These experiments indicate that during GvHR enteropathy the ability of the intestine to convert gliadin into a tolerogenic form is lost. Defective antigen gut processing may contribute to the observed failure in oral tolerance induction.

Animals↗