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PubMed2004

The interferon gamma gene in celiac disease: augmented expression correlates with tissue damage but no evidence for genetic susceptibility.

Celiac disease (CD) is a complex genetic disorder characterized by gluten intolerance. The Th1 immune response, with a key position for interferon gamma (IFN-gamma), is an important determinant of intestinal remodeling in CD. We aimed at further ascertaining the role of IFN-gamma, either as a genetic factor in the etiology, or as a facilitator of disease initiation/progression. Duodenal biopsies were sampled across distinct histopathological stages of the disease, including refractory CD (RCD), and used to determine IFN-gamma gene (IFNG) expression by real-time RT-PCR. INFG expression correlated with the extent of tissue restructuring, reaching a 240-fold higher expression in total villous atrophy compared to healthy tissue. CD and RCD patients with similar lesions had comparable expression levels. Interestingly, patients in complete remission still had 7.6-fold residual over-expression. An INFG marker was tested in three cohorts of Dutch patients for both genetic linkage and association. Linkage analysis yielded no significant scores for IFNG or its flanking markers. In addition, IFNG allele frequencies were not differently distributed between cases and controls. Likewise, all alleles were randomly transmitted to affected children in parents-case trios. There is no evidence for IFNG as a predisposing gene in CD, despite its enhanced expression in patients in complete remission.

Adult↗
PubMed2006

Association analysis of MYO9B gene polymorphisms with celiac disease in a Swedish/Norwegian cohort.

Association between myosin IXB (MYO9B) gene variants and celiac disease (CD) has been reported in a study of a Dutch cohort. Six single nucleotide polymorphisms (SNPs) within the 3' part of the MYO9B gene showed significant genetic association and formed an associated haplotype. The current study aimed to replicate these findings in a Swedish/Norwegian cohort. Genotyping of the three SNPs which tagged the associated haplotype was performed in a CD family dataset (n = 326) and in an additional set of healthy controls (n = 562). Although our material provided reasonable power to detect the previously observed association, we were unable to replicate association with these SNPs. Lack of reproducibility could be explained by no or negligible contribution of MYO9B to the genetic predisposition to CD in the Swedish/Norwegian population. Alternatively, it might be due to variable linkage disequilibria in distinct populations in the tested SNPs and a causative mutation yet to be identified or to false positive findings (type I error) in the Dutch study.

Celiac Disease↗
PubMed2000

Can zinc deficiency be used as a marker for the diagnosis of celiac disease in Turkish children with short stature?

BACKGROUND: It is generally accepted that celiac disease (CD) must always be considered when dealing with growth failure in children. Therefore, it is important to develop screening tests for detecting patients that need an intestinal biopsy. The aim of the present study was to investigate the value of plasma zinc levels for the diagnosis of monosymptomatic CD in short-statured children. METHODS: Fourty-nine children with a short stature and 34 healthy controls were investigated. Plasma zinc levels were assayed by atomic absorption spectrophotometry in short-statured children and controls. All patients with short stature underwent endoscopic small intestinal biopsy. RESULTS: Duodenal mucosal histopathology was normal in 25 children. Low plasma zinc values were observed in 54.2% of patients with CD, 32.0% of patients with idiopathic short stature and 14.8% of controls. The mean values of plasma zinc levels were not significantly different among the three groups. Sensitivity, specificity and the positive and negative predictive values for plasma zinc were 45.8, 76.0, 64.7 and 59.4%, respectively. CONCLUSIONS: These results indicate that zinc deficiency is an important problem in CD children with short stature; however, plasma zinc levels are not useful as a screening test for selecting patients for jejunal biopsy.

Biomarkers↗
PubMed2004

Clinical features of children with screening-identified evidence of celiac disease.

OBJECTIVE: At-risk groups commonly undergo screening for autoantibodies associated with celiac disease (CD). However, the clinical significance of a positive test remains uncertain. The objective of this study was to evaluate growth and clinical features of children who test positive for an autoantibody associated with CD. METHODS: A case-control study of Denver area healthy infants and young children with and without CD autoantibodies was conducted. A cohort of HLA-characterized children were followed prospectively since birth for the development of immunoglobulin A antitissue transglutaminase autoantibodies (TG). Clinical evaluation, questionnaire, blood draw, and small bowel biopsy were performed. Growth and nutrition and frequency of positive responses were measured. RESULTS: Compared with 100 age- and gender-matched TG-negative controls, 18 TG-positive children, 5.5 +/- 0.5 years of age, had a greater number of symptoms and lower z scores for weight-for-height and for body mass index. Responses that were independently associated with TG-positive status were irritability/lethargy, abdominal distention/gas, and difficulty with weight gain. CONCLUSIONS: Screening-identified TG-positive children demonstrate mild alterations in growth and nutrition and report more symptoms than control subjects. Additional study is needed on the benefit and risk of identifying CD in at-risk groups.

Autoantibodies↗
PubMed2006

Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease.

Recent studies have demonstrated the importance of TLR signaling in intestinal homeostasis. Celiac disease (CD) is an autoimmune enteropathy triggered in susceptible individuals by the ingestion of gliadin-containing grains. In this study, we sought to test the hypothesis that gliadin initiates this response by stimulating the innate immune response to increase intestinal permeability and by up-regulating macrophage proinflammatory gene expression and cytokine production. To this end, intestinal permeability and the release of zonulin (an endogenous mediator of gut permeability) in vitro, as well as proinflammatory gene expression and cytokine release by primary murine macrophage cultures, were measured. Gliadin and its peptide derivatives, 33-mer and p31-43, were found to be potent inducers of both a zonulin-dependent increase in intestinal permeability and macrophage proinflammatory gene expression and cytokine secretion. Gliadin-induced zonulin release, increased intestinal permeability, and cytokine production were dependent on myeloid differentiation factor 88 (MyD88), a key adapter molecule in the TLR/IL-1R signaling pathways, but were neither TLR2- nor TLR4-dependent. Our data support the following model for the innate immune response to gliadin in the initiation of CD. Gliadin interaction with the intestinal epithelium increases intestinal permeability through the MyD88-dependent release of zonulin that, in turn, enables paracellular translocation of gliadin and its subsequent interaction with macrophages within the intestinal submucosa. There, the interaction of gliadin with macrophages elicits a MyD88-dependent proinflammatory cytokine milieu that facilitates the interaction of T cells with APCs, leading ultimately to the Ag-specific adaptive immune response seen in patients with CD.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Pattern of human leukocyte antigens in Turkish children with celiac disease.

BACKGROUND: Regional variations in the human leukocyte antigen (HLA) distribution patterns of celiac disease (CD) have been reported. The aim of the present study was to assess the distribution of HLA class I and class II in Turkish children with CD and to compare the findings with a control group. METHODS: Human leukocyte antigen typing was performed in 33 children with CD and in 77 healthy individuals, who served as controls, by using standard National Institutes of Health lymphocytotoxicity techniques. RESULTS: A positive association was found between HLA A2 (42 vs 19% for sick subjects compared with healthy controls, respectively), B8 (39 vs. 9% for sick subjects compared with healthy controls, respectively), CW7 (45 vs. 25% for sick subjects compared with healthy controls, respectively), DR3 (70 vs. 17% for sick subjects compared with healthy controls, respectively), DR7 (30 vs. 13% for sick subjects compared with healthy controls, respectively) and DQ2 (52 vs. 34% for sick subjects compared with healthy controls, respectively). The combinations of DR3-DQ2 (30 vs. 12% for sick subjects compared with healthy controls, respectively), DR3-DR4 (21 vs. 1% for sick subjects compared with healthy controls, respectively) and DR7-DQ2 (21 vs. 6% for sick subjects compared with healthy controls, respectively) were also found to be significantly important in children with CD. The highest relative risk (RR) was for HLA B8 in class I (RR 6.50), for DR3 (RR 11.30) in class II and for combination of DR3-DR4 (RR 20.46). The highest etiologic fraction (EF) was for the DR3 antigen (EF 0.55). CONCLUSIONS: The present study emphasizes that HLA genotypes are an important background to CD development, but some additional susceptibility factors remain to be identified.

Celiac Disease↗
PubMed2003

Association between migraine and Celiac disease: results from a preliminary case-control and therapeutic study.

OBJECTIVES: Subclinical celiac disease (CD) has been associated with various neurological disorders, the most common being neuropathy and cerebellar ataxia. The aims of the present study were to assess the following: 1) the prevalence of CD in patients affected by migraine; 2) whether there are regional cerebral blood flow abnormalities in migraine patients with CD compared to migraine patients without CD; and 3) the effects of a gluten free diet in migraine patients with CD. METHODS: A total of 90 patients affected by idiopathic migraine were enrolled, and 236 blood donors were used as controls. Serum IgG antitransglutaminase (TgA) and IgA antiendomysial (EmA) were measured. In positive cases, diagnosis was confirmed endoscopically. A gluten free diet was started in the patients diagnosed with CD, who were followed for 6 months. A single photon emission CT brain study was performed before and after a gluten free diet. RESULTS: Four of 90 (4.4%; 95% CI = 1.2-11.0) migraine patients were found to have CD compared with 0.4% (95% CI = 0.01-2.3) blood donor controls (p < 0.05). During the 6 months of gluten free diet, one of the four patients had no migraine attacks, and the remaining three patients experienced an improvement in frequency, duration, and intensity of migraine. Single photon emission CT studies showed a regional baseline reduction in brain tracer uptake in all four patients. Such reduction in uptake completely resolved at follow-up. CONCLUSIONS: Our results suggest that a significant proportion of patients with migraine may have CD, and that a gluten free diet may lead to a improvement in the migraine in these patients.

Adult↗
PubMed2002

ELISA of anti-endomysial antibodies in the diagnosis of celiac disease: comparison with immunofluorescence assay of anti-endomysial antibodies and tissue transglutaminase antibodies.

BACKGROUND: Celiac disease is common in both children and adults. Small intestinal biopsy is mandatory for establishing a diagnosis. Anti-endomysial antibodies, detected by immunofluorescence, have a sensitivity and specificity close to 100% in the diagnosis of CD. Recently, tissue transglutaminase has been identified as the target autoantigen of antibodies against endomysium, and TTG antibodies are comparable to EMA-IMF in the diagnosis of CD. OBJECTIVE: To evaluate a new enzyme-linked immunosorbent assay kit for EMA, compared to EMA-IMF and TTG antibodies in the diagnosis of CD. METHODS: Our study population included all subjects with positive EMA-IMF who underwent intestinal biopsy (n = 21). From the same sera, TTG antibodies and EMA-ELISA were determined, and all antibody results were compared to the biopsy findings. RESULTS: EMA-IMF was able to predict biopsy findings of CD in 19 of 21 cases (90.5%). When patients with biopsy findings compatible with CD and positive EMA-IMF (n = 19) were tested for EMA-ELISA and TTG antibodies, 18 of the 19 were positive for both EMA-ELISA and TTG antibodies. A significant correlation was found between EMA-ELISA and TTG antibody titers (r = 0.74, P < 0.001). CONCLUSIONS: Our study demonstrates that EMA-ELISA is comparable to TTG antibodies in the diagnosis of CD, and supports the use of EMA-ELISA as a serologic marker for this disease.

Autoantibodies↗
PubMed2002

Postmenopausal osteoporosis and celiac disease.

Individualizing risk factors is the most important tool to prevent late consequences of menopause. Celiac disease is a predisposing condition not very considered for some postmenopausal diseases, such as postmenopausal osteoporosis. In this review the authors examine climacteric conditions that could be heightened by a celiac status especially if disregarded and untreated.

Celiac Disease↗
PubMed1964

[CELIAC DISEASE].

Explore the source record for details and available documents.

Celiac Disease↗
PubMed2004

Latent autoimmune diabetes mellitus in children (LADC) with autoimmune thyroiditis and Celiac disease.

Latent autoimmune diabetes mellitus in adults (LADA) is characterized by clinical presentation as type 2 diabetes mellitus after 25 years of age, initial control achieved with oral hypoglycemic agents for at least 6 months, presence of autoantibodies and some immunogenetic features of type 1 diabetes mellitus. An 8.3 year-old girl was referred to our pediatric endocrinology department because of incidental glucosuria. She did not complain of polyuria, polydipsia, or weight loss. Her body mass index (BMI) was at the 80th percentile. Fasting glucose was 126 mg/dl, and OGTT glucose level at 120 min was 307 mg/dl. Although C-peptide levels were normal, her first phase insulin response (FIR) was lower than the 1st percentile. Anti-insulin antibody (AIA), islet cell antibody (ICA), and anti-glutamic acid decarboxylase (antiGAD) were negative. According to the clinical and laboratory findings, she was diagnosed as having type 2 diabetes mellitus. She was started with oral anti-diabetic treatment for a period of 1 year. Insulin had to be initiated for worsening of HbA1c levels. In the fourth year of follow-up, she was admitted to our hospital with diabetic ketoacidosis although she was on an intensive insulin regimen. At this time, C-peptide levels were low, antiGAD and AIA were positive with HLA DR3/DQ2 haplotype. In addition, her thyroid peroxidase antibody and endomysium antibody were found to be high at follow-up. Small intestinal biopsy revealed celiac disease. This patient may represent the first case of latent autoimmune diabetes mellitus in children (LADC) with autoimmune thyroiditis and celiac disease.

Blood Glucose↗
PubMed2001

Health-related quality of life in children with celiac disease.

We have investigated the health-related quality of life of children with celiac disease (n = 133) using two generic and one disease-specific questionnaires. In general, the children reported an adequate quality of life, similar to that of the reference sample (n = 1183).

Adolescent↗
PubMed2006

[Prevalence of celiac disease in Turner syndrome].

INTRODUCTION AND AIM: Percentage of coeliac disease among patients with Turner syndrome is given differently in a few publication. The aim of the study was to assess prevalence of celiac disease in Turner syndrome. PATIENTS AND METHODS: Serological screening of coeliac disease were performed in 63 patients with Turner syndrome during the last 11.5 years (since 1994). Serological investigations were repeated yearly since 2003 in all patients, and the results of screening of new patients were completed. Theirs first case of coeliac disease was announced in 2004 in Gyermekgyógyászat (Hun). Further positive serological results were found after publication of the first case. RESULTS: Positive results were found in seven of 63 patients (two EmA and five antitransglutaminase IgA positivity). Intestinal biopsy was applied in all 7 cases. Coeliac disease was revealed by histologic analysis in the five cases - 5/63 (7.9%). CONCLUSION: The prevalence of coeliac disease in Turner syndrome seems to be higher than in general population. This can play role in the insufficient effect of growth hormone therapy in the affected patients. The high prevalence indicates that the connection between these disorders can not be coincidental. Their cases and the available data from the publications indicate that screening of coeliac disease in patients with Turner syndrome should be performed and intestinal biopsy is recommended in positive cases.

Adolescent↗
PubMed2003

Prevalence of antitissue transglutaminase antibodies in different degrees of intestinal damage in celiac disease.

GOALS: Although anti-tissue transglutaminase antibodies (anti-tTG) are effective for celiac disease (CD) routine laboratory screening, there are no studies evaluating correlation between degree of intestinal damage and positivity to anti-tTG. Since recent studies showed that anti-gliadin (AGA) and anti-endomysium (EMA) antibodies are ineffective in diagnosing mild gluten-sensitive enteropathy, the aim of this study was to evaluate the prevalence of anti-tTG in different degrees of intestinal damage of celiac patients and whether there is a correlation between serum value of anti-tTG and the degree of histologic damage. STUDY: We studied 119 consecutive adult patients affected by CD (47 men and 72 women; mean age, 28 years; range, 22-51 years). All patients were stratified for histologic damage according to Marsh classification, and in all of them an anti-tTG evaluation was performed. RESULTS: Marsh I lesions were present in 13 patients (10.92%), Marsh II in 24 anti-tTG (20.16%), Marsh IIIa in 27 anti-tTG (22.68%), Marsh IIIb in 31 anti-tTG (26.05%) and Marsh IIIc in 24 anti-tTG (20.16%). Anti-tTG positivity was ranging from 1 of 13 anti-tTG (7.69%) in Marsh I lesions to 23 of 24 anti-tTG (95.83%) in Marsh IIIc lesions respectively ( P< 0.005), while mean serum value of anti-tTG ranged from 3.61 (range, 0.7-9.2) UA/mL in Marsh I lesions to 7.3 (range, 1-25.1), 18.5 (range, 1.8-56.2), 36 (range, 3.7-83.5) and 74.95 (range, 6.5-257) UA/mL in Marsh II, IIIb and IIIc lesions respectively (P < 0.005). CONCLUSIONS: Our study showed that anti-tTG prevalence and their mean serum value was higher in celiacs with severe enteropathy (Marsh IIIb-c lesions) than in those showing slight enteropathy (Marsh I-IIIa). So, serologic tests without histologic evaluation may underestimate the real prevalence of CD and there is the risk of delaying the diagnosis of CD in patients who run an increased risk of deficiencies, non-malignant conditions and malignancy.

Adult↗
PubMed2006

Prevalence and demographic characteristics of celiac disease among blood donors in Ribeirão Preto, State of São Paulo, Brazil.

Celiac disease (CD) is an underdiagnosed disease occurring in different clinical forms. This study aimed to determine the prevalence of CD among blood donors from Ribeirão Preto, Brazil, and to study some demographic characteristics of celiac patients. Blood samples from 3000 blood donors were tested for the presence of tissue transglutaminase antibody and positive samples were tested for endomysial antibody. Donors positive to both tests were referred for clinical evaluation and for a jejunal biopsy. Twenty-four samples were moderately/strongly positive for transglutaminase, with 9 of them being endomysial negative and 15 positive. Of the 13 biopsies obtained from 12 females and 1 male, 1 was classified as Marsh grade IV, 4 as grade III, 2 as grade II, 4 as grade I, and 2 as grade 0. Estimated prevalence was therefore 1:273 (0.33%; 95% CI, 0.127 to 0.539). The 1:273 estimated prevalence of CD detected indicates that the disease is not rare in Brazil. The frequency was higher among females and among individuals of European descent, with a significantly higher frequency for a family history of digestive tract cancer or epilepsy.

Adolescent↗
PubMed1998

[Celiac disease of the adult following orthotopic liver transplantation. Description of a case].

A case of celiac disease of the adult is herein described in a patient with a history of orthotopic liver transplantation because of cirrhosis due to hepatitis C virus. The patient presented with a decrease in the levels of cyclosporinemia, diarrhea and an increase in transaminases. This is an infrequent form of presentation leading to differential diagnosis with a complication related to the liver disease.

Celiac Disease↗