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A case of prurigo nodularis (Hyde's prurigo) preceding by 15 years the diagnosis of celiac disease is presented. In particular, the association between the clinical course of prurigo nodularis and the compliance with gluten-free diet is reported and discussed.
To know the prevalence of celiac disease (CD) in a group of children and adolescents with type I diabetes mellitus. A cross sectional study was conducted at the Instituto Materno Infantil de Pernambuco (IMIP) in March 2000. The sample consisted of 19 children and adolescents with type I diabetes mellitus that had the human anti-tissue transglutaminase antibodies assessed using kits from the Eurospital Laboratory. In case of positive results it was realized small intestine biopsy to confirm the diagnosis. For the calculation of the prevalence of CD it was considered the number of patients with serum positive histological alterations of the mucous membrane of the small intestine compatible with CD. Four patients presented serum positivity for human anti-tissue transglutaminase antibodies with a serum prevalence of 21% (4/19). Out of these four subjects, three who accomplished small intestine biopsy presented histological alterations compatible with CD. The prevalence of CD in this group was 15.8% (3/19). The prevalence of CD in this study group was high, suggesting that those with type I diabetes mellitus should be led as a group of high risk to develop this disease.
This study will discuss our current understanding of celiac disease (CD), thyroid disorders, and atlanto-axial instability, three important areas of medical management in individuals with Down syndrome (DS). In this study, we highlight our current knowledge, as well as what we need to study in order to gather the necessary data to refine the empirically based screening protocols which are now in place.
After 5 years of treatment, 22 patients with celiac disease, diagnosed by means of serologic mass screening (mean age, 17.9 years), showed a lower compliance with a gluten-free diet and frequent positivity of serum anti-endomysium antibodies (32%) in comparison with a group of 22 age-matched patients diagnosed because of "typical" symptoms during childhood.
A patient with celiac disease and relapsing-progressive symptoms suggesting brainstem and cerebellar involvement underwent serial MRIs. The first examination revealed multiple enhancing and nonenhancing lesions. Thereafter, a large enhancing cerebellar lesion appeared, followed by severe cerebellar atrophy. The presence of structural neuronal damage was confirmed by proton MR spectroscopy and magnetization transfer imaging. MRI results and CSF findings suggested that neurologic complications were more likely due to an inflammatory process.
Histological confirmation of infiltrative lesions via small bowel biopsy is the gold standard for diagnosing celiac disease. Four serum antibody assays may serve as a first-step diagnostic tool to identify biopsy candidates: immunoglobulin A tissue transglutaminase (IgA tTG), IgA endomysial antibody (IgA EMA), IgA antigliadin antibody (IgA AGA), and IgG antigliadin antibody (IgG AGA). IgA tTG and IgA EMA offer the best diagnostic accuracy. Patients with selective IgA deficiency may have falsely negative IgA assays (strength of recommendation [SOR]: B, based on a systematic review, multiple small cross-sectional studies, and expert opinion).
HLA phenotypes of 64 Italian pediatric patients with celiac disease (CD) were compared with those of a group of healthy controls. DR3 and DR7 are significantly increased as reported in other populations. In addition an increase of heterozygotes DR5/DR7 was observed in our patients. The Hardy-Weinberg distribution in the patients group shows a disequilibrium due to the genotype DR5/DR7. Our data confirm that more than one HLA gene product is associated with CD: one with DR3 and the other with DR7.
Our aim was to evaluate whether increased enterocyte apoptosis was responsible for mucosal flattening in celiac disease (CD), and, since the mechanisms responsible for tissue injury in this condition are unknown, we studied the possibility that the Fas-Fas ligand (FasL) system may be involved. Endoscopic duodenal biopsy specimens from 12 patients with untreated and 12 with treated CD and 12 control subjects were evaluated for enterocyte apoptosis by the terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick-end labeling assay and for Fas and FasL expression by immunohistochemistry. A coculture of isolated enterocytes (targets) and purified lamina propria mononuclear cells (LPMCs) (effectors) was performed in the absence or presence of an antagonistic ZB4 anti-Fas antibody. We found a significant correlation between the degree of villous atrophy, morphometrically evaluated, and the level of enterocyte apoptosis, suggesting that mucosal flattening is a consequence of exaggerated epithelial cell death. Most celiac enterocytes express Fas, and LPMCs express FasL. The abolishment of enterocyte apoptosis observed in the presence of ZB4 antibody suggests that enterocytes are potential targets of lymphocyte infiltrate. These results directly demonstrate that FasL-mediated apoptosis is a major mechanism responsible for enterocyte death in CD.
BACKGROUND: Recent evidence suggest that the innate immune system is implicated in the early events of celiac disease (CD) pathogenesis. In this work for the first time we have assessed the relevance of different proinflammatory mediators typically related to innate immunity in CD predisposition. METHODS: We performed a familial study in which 105 celiac families characterized by the presence of an affected child with CD were genotyped for functional polymorphisms located at regulatory regions of IL-1alpha, IL-1beta, IL-1RN, IL-18, RANTES and MCP-1 genes. Familial data was analysed with a transmission disequilibrium test (TDT) that revealed no statistically significant differences in the transmission pattern of the different genetic markers considered. RESULTS: The TDT analysis for IL-1alpha, IL-1beta, IL-1RN, IL-18, and MCP-1 genes genetic variants did not reveal biased transmission to the affected offspring. Only a borderline association of RANTES promoter genetic variants with CD predisposition was observed. CONCLUSION: Our results suggest that the analysed polymorphisms of IL-1alpha, IL-1beta, IL-1RN, IL-18, RANTES and MCP-1 genes do not seem to play a major role in CD genetic predisposition in our population.
OBJECTIVE: Patients with autoimmune Addison's disease (AAD) are prone to develop other autoimmune manifestations. An increased prevalence of celiac disease (CD) has recently been demonstrated in Northern European patients with AAD. IgA deficiency is the most frequent type of immunodeficiency among humans and is present in about one in every 600 individuals in the population. IgA deficiency is frequent in patients with other autoimmune diseases, but data concerning AAD are still unavailable. DESIGN: The aim was to define the prevalence of CD and of IgA deficiency in a group of Italian patients with AAD. METHODS: One hundred and nine patients with AAD were enrolled and examined for tissue transglutaminase autoantibodies of the IgA class, circulating levels of IgA and adrenal cortex antibodies. RESULTS: Two (1.8%) of the patients were affected by already diagnosed CD and were already on a gluten-free diet. Out of the remaining 107 patients, four (3.7%) were found to be positive for IgA antibodies to human tissue transglutaminase. Three of the four patients who were positive for tissue transglutaminase autoantibodies agreed to undergo endoscopy and duodenal biopsies and, in one, a latent form of CD was identified. The clinical, silent or latent form of CD was present in six out of 109 (5.4%). This prevalence was significantly higher (P = 0.0001) than that reported for the Northern Italian population which was equal to 0.063%. Specifically, CD was present in 12.5% of the autoimmune polyglandular syndrome (APS) type 1 cases, in four out of 60 (6.7%) of the APS type 2 cases and in one out of 40 (2.5%) of the isolated AAD cases. IgA deficiency was present in two out of 109 patients (1.8%), all of whom had normal IgG anti-gliadin. Autoantibodies to the adrenal cortex were detected in 81 out of 109 patients (74.3%). CONCLUSIONS: In patients with AAD there is a high prevalence of both CD and IgA deficiency. Consequently, it is important to screen for CD with tissue transglutaminase autoantibodies of the IgA class and for IgA levels.
This paper underlines the need of developing animal models to study the diverse complications of celiac disease (CD). CD is a multifactorial condition requiring both an exogenous element (gluten) and complex genetic factors; moreover, CD is associated to several endocrine, immune and reproductive diseases, whose onset may be influenced by other environmental factors as well. In particular, the intestinal absorption of exogenous factors may be important for the outcome of CD as well as of the associated diabetes and/or thyroiditis. Presently, there are no adequate animal models for the systemic complications of CD; in particular, there are no gene knock-out models. However, models are available as regards either gluten enteropathy, such as Irish Setter and Balb/c e BDF1 mouse strains, and endocrine-immune diseases associated with CD, such as BB rats and NOD mice. A deeper exploitation of the available models could provide important information on the factors modulating intestinal permeability, the pathogenesis of extraintestinal alterations and the interactions between gluten and other metabolic, nutritional and environmental factors. The elaboration of in vivo models requires a sound basis of knowledge at molecular level, as well as the modulation of the metabolic alteration through relevant exogenous factors, first of all the dietary assumption of gluten. Therefore, the availability of experimental models may provide significant advances on the prevention and treatment, allowing a complete analysis of affected organisms as well as the use of pharmacological and/or immune stimuli; more information may be also derived on the possible long-term effects of gluten traces in CD-affected subjects, thus reducing the need for lengthy clinical studies.
This report shows the absolute genetic linkage of celiac disease (CD) to the HLA-DQ region, and supports the fact that dermatitis herpetiformis (DH) follows the same pattern of HLA-mediated susceptibility in extensive series of Caucasian Spanish patients. Ninety-five percent of CD (201 of 212) and 100% of DH (55) patients could produce DQ alpha 1*0501-DQ beta 1*02 heterodimers. Negative CD patients for this combination were mostly DR4-DQ8 (DQA1*03-DQB1*0302) (9 OF 11), along with a restricted number of complementary chromosomes. Comparison of observed and expected DQA1-DQB1 genotype distributions (Hardy-Weinberg equilibrium) showed that the excess of patients with DQB1*02 in double doses would be the consequence for which this allele should be complemented by DQA1*0501. Homozygosity for DQA1*0501 would restrain susceptibility to CD and DH.
Bone turnover impairement and low bone density in 25-year-old man with active celiac disease was presented. The patient refused gluten-free diet compliance and clinically showed doughy abdomen, hyperpigmentation, finger clubbing and koilonychia. In serum, we obtained about 2-fold of formation markers (osteocalcin, bone alkaline phosphatase) and and 5-fold higher levels of resorption marker (collagen type I crosslinked C-telopeptide). The concentration of osteoprotegerin was slightly above normal range. We observed the trace amounts of 25-(OH)D in serum whereas the level of parathormone was 2-fold higher than in controls. Serum calcium and phosphorus were often below normal range. In dual X-ray absorptiometry (DXA) whole-body bone density was remarkably reduced. Our results suggest, that on gluten-containing diet the patient will develop lower bone mineral density and higher risk of fractures and skeletal deformities.
Anti-endomysium antibodies (AEM) fail to identify all untreated celiac disease (CD) patients. This study aims to determine if additional serology, in particular, IgA anti-tissue transglutaminase (tTG) antibodies, increases detection. Fifty-three biopsy-proven untreated CD patients (39 women, 14 men; median age 51 years) and 65 control patients with normal duodenal histology (46 women, 19 men; age range 17-90 years, median 45 years) were prospectively studied. Serum total IgA, IgA anti-tTG, IgA AEM, IgA anti-gliadin (AGA) and IgG AGA antibodies were measured. Thirteen (25%) CD patients were AEM negative. None were IgA deficient. Three AEM-negative CD patients had a raised IgA anti-tTG and IgA AGA. IgG AGA was raised in 10 AEM-negative CD patients, but also in 14/65 (22%) of controls. In conclusion, AEM-negative CD is common and detection is only modestly enhanced by testing for IgA anti-tTG antibodies. Duodenal biopsy is still recommended for the accurate diagnosis of CD.
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.
The HLA-associated susceptibility to develop celiac disease (CD) seems mainly to be conferred by a particular HLA-DQ heterodimer encoded by the DQA1*0501 and DQB1*0201 genes either in cis or in trans position. To study the possible influence of DRB1 or other DQA1 and DQB1 alleles on the CD susceptibility conferred by these DQ genes, we performed genomic HLA typing of 94 CD patients, selected those who carried at least one copy of the DRB1*0301-DQA1*0501-DQB1*0201 haplotype (N = 89) and compared them to 47 random, healthy Norwegians matched with the patients to carry at least one copy of the above haplotype. We found an excess of DQB1*0201 homozygosity in the patients. This was due to an increased frequency of the DRB1*0301-DQA1*0501-DQB1*0201 and DRB1*0701-DQA1*0201-DQB1*0201 haplotypes present on the other chromosome. We propose that, in individuals carrying the DQA1*0501 and DQB1*0201 alleles, the presence of a second copy of the DQB1*0201 allele increases susceptibility to CD.
Serum IgA-antigliadin antibodies (SAGA) were measured by ELISA in 46 children with proven celiac disease (CD), in 52 children with probable CD, and in 85 control subjects. Small intestinal biopsy was done within 3 months of the SAGA determination in all children. In the proven and probable CD groups, SAGA values were greater than 70 mu/ml in 76 of 82 biopsies that showed severe mucosal damage, but in only 4 of 31 with normal mucosa; thus specificity was 87.1% and sensitivity 92.7%. In the control group, only 12 of 85 children with normal biopsies had a similarly raised SAGA value. SAGA levels decreased significantly when a gluten-free diet was instituted, and rose to abnormal levels in most children on gluten challenge. IgA-SAGA can be used for monitoring dietary compliance during different phases of CD. Although it may help in selecting some children who are evaluated for the possibility of CD, for small intestinal biopsy, children with active CD may show negative SAGA values. The test should therefore not be used as the sole or final determining factor for the performance of small intestinal biopsy. In the proper clinical setting, a biopsy should be done, regardless of the SAGA results.
Researched from immunologic and genetic point of view, 40 patients with Celiac Diseases confirmed and under-treatment. The results were compared with a group of 257 healthy people. The immunologic studies: leucocytes and lymphocytes in blood, the subpopulation of lymphocytes T and B, The immune-reaction studies of immunoglobulin Ig G, Ig M, Ig A and component C III complement didn't show difference between the comparative groups justified perhaps because the group of patients were under-treatment. In the antigen erythrocyte A B O and RHO (A), we can only in those assert that there is an increase of A and B group between the patients than who have O, and they were less exposed to get the disease. Between the histocompatibility antigen, the low presence of A9 B5 B7 BW16 antigen in Celiac patients could be a sign of protection against the disease, contrarily the presence of A1 B8 Dr3 Dr7 could indicate the high risk to get the disease. These finding confirm that the antigen group connected with the major System of histocompatibility, showed the susceptibility to suffer the disease.