Jump to content
  • Join Our Community!

    Do you have questions about celiac disease or the gluten-free diet?


Recent Research Articles

Rate this topic

Recommended Posts

I thought I'd do some updating of my research on celiac disease, and am going to link and include abstracts for the recent, seemingly-meaningful abstracts that I'm picking up off pubmed (just Oct. 05 through Jan. 06, and not all of them). (This could be a loooong post. :-) )

(Don't forget, while reading this, that just because an author concludes something that it is true. There are a few conclusions here that seem like illogical conclusions, even based on what they write themselves, to me. And studies are done that contradict other ones all the time. :-) )

Molecular mechanisms responsible for the involvement of tissue transglutaminase in human diseases: Celiac Disease.

Tissue transglutaminase (tTG or TG2; E.C. belongs to the transglutaminase family, a group of closely related enzymes that share the ability to catalyze the cross-linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. tTG is a multifunctional enzyme since it is also capable of catalyzing other biochemical reactions. The distribution and physiological roles of tTG have been widely studied in numerous cell types and tissues, but only recently its role in human diseases has started to be clarified. For example, transglutaminase activity has been hypothesized to be involved in the pathogenetic mechanisms responsible for several human diseases, including neurodegenerative diseases, such as polyglutamine diseases hitherto identified. Among human diseases, a large and recent series of studies have clearly shown that the activity of the tTG is critical for a very diffuse human pathology known as Celiac Disease. This disease is due to intolerance to a food component, gliadin, and is characterized by a very complex clinical syndrome, including gastrointestinal pathological manifestations, often associated with extra-intestinal manifestations. Interestingly, a subset of celiac patients also develops certain neurological disorders. In this review we describe the roles played by tTG in the molecular mechanisms responsible for pathophysiology of Celiac Disease.

Increasing numbers at a specialist coeliac clinic: Contribution of serological testing in primary care.

BACKGROUND: Serological testing, using IgA class endomysial and tissue transglutaminase antibodies has high sensitivity and specificity for coeliac disease and allows case finding by clinicians other than gastroenterologists. We reviewed new coeliac patients seen over a 9-year period to determine how the availability of serology, particularly to primary care physicians, has changed rates and sources of diagnosis. METHODS: Files of patients attending a specialist coeliac clinic who were diagnosed from 1996 through 2004 were reviewed. Patients with villous atrophy consistent with gluten sensitive enteropathy (Marsh III) on duodenal biopsy were selected. Data analysed included clinical characteristics, endomysial and tissue transglutaminase antibodies status and source of request for serology. RESULTS: Over the study period 347 new coeliac patients, comprising adults and children aged 10 years and over, were identified, of whom 163 (47%) were identified by serological testing in primary care, 152 (44%) at the hospital gastroenterology department and 32 (9%) by other physicians in secondary care. Over three consecutive 3-year periods, the percentage of patients identified in primary care rose from 28% through 47% to 60%, with a rise in total numbers diagnosed from 93 through 118 to 136. There was no change in patient clinical characteristics over the study period. Though tissue transglutaminase antibodies were less sensitive than endomysial antibodies, combined testing obtained a sensitivity of over 90%. Patients identified in primary care were significantly younger and more likely to present with diarrhoea as a primary symptom. CONCLUSION: Currently over half of our coeliac patients are identified by serological testing in primary care, which has resulted in an overall rise in diagnosis rates. Primary care practitioners have an important role in the diagnosis of coeliac disease, particularly of patients who present with non-gastrointestinal symptoms. The contribution of specialists other than gastroenterologists in secondary care is disappointing and may improve with directed education.

Do patients with unrecognized coeliac disease present as an emergency?

Screening studies of healthy volunteers have determined that coeliac disease affects 1% of the European population. Despite this the majority of cases are unrecognized. Coeliac disease may occasionally present as an acute emergency. Recent data, however, suggest that cases of undiagnosed coeliac disease may present to emergency departments with nonspecific abdominal pain. This review provides an update of the published data on coeliac disease. We discuss the relationship between coeliac disease and abdominal pain and ways in which this may change emergency physicians practice.

Adult coeliac disease diagnosed by endoscopic biopsies in the duodenal bulb.

Multiple endoscopic biopsies in the descending duodenum are usually recognized as the standardized method for the evaluation of mucosal changes in coeliac disease. Generally, the duodenal bulb is not considered a useful site for biopsies, due to some difficulties in histological evaluation. A case in which the diagnosis of coeliac disease was possible only with the aid of biopsies in the duodenal bulb is reported; noteworthy, this unusual site for biopsies was strongly suggested by the presence of a mosaic-like endoscopic appearance. Only few cases (mainly in childhood) have been reported in which diagnosis was made with the aid of biopsies in the duodenal bulb. This occurrence suggests that performing biopsies only in the descending duodenum may not be sufficient in some patients, and raises the question of whether obtaining specimens both from the first and the second part of the duodenum might be a more correct and complete approach to this problem.

Predisposing HLA-DQ2 and HLA-DQ8 haplotypes of coeliac disease and associated enteropathy in microscopic colitis.

OBJECTIVE: To assess the presence of both genetic and serological markers of coeliac disease in patients with microscopic colitis, and whether there was associated enteropathy. METHODS: HLA-DQ2, HLA-DQ8, serum immunoglobulin A-antiendomysial and immunoglobulin A-anti-tissue transglutaminase antibodies were investigated in 59 patients with microscopic colitis. Seventy healthy subjects acted as the control group. Endoscopic biopsies from the distal duodenum were obtained in DQ2-positive or DQ8-positive patients. Patients with histological changes compatible with gluten-sensitive enteropathy were started on a gluten-free diet. RESULTS: Seventeen of 70 (24.3%) healthy controls were DQ2-positive. Twelve of 25 (48%) patients with lymphocytic colitis (P=0.027 versus controls), and 11 of 34 (32.3%) with collagenous colitis (P=0.38 versus controls) were DQ2-positive. There were no differences in the frequency of DQ8-positivity. The coeliac serology was positive in one patient. Duodenal biopsies were performed in 23 DQ2-positive and/or DQ8-positive patients. None had villous atrophy (Marsh III lesion) (0%; 95% confidence interval, 0-6.1). A Marsh type I lesion was found in four patients. Three of these patients were put on a gluten-free diet with disappearance of diarrhoea. CONCLUSIONS: The results suggest that there is an association of lymphocytic colitis with HLA-DQ2 genes, which might be relevant in the pathogenesis of this disease. The association of microscopic colitis with Marsh type III coeliac disease seems to be rare, making it unnecessary to routinely screen for coeliac disease in microscopic colitis patients.

Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect.

Celiac disease is probably the best-understood immune-related disorder. The disease presents in the small intestine and results from the interplay between multiple genes and gluten, the triggering environmental factor. Although HLA class II genes explain 40% of the heritable risk, non-HLA genes accounting for most of the familial clustering have not yet been identified. Here we report significant and replicable association (P = 2.1 x 10(-6)) to a common variant located in intron 28 of the gene myosin IXB (MYO9B), which encodes an unconventional myosin molecule that has a role in actin remodeling of epithelial enterocytes. Individuals homozygous with respect to the at-risk allele have a 2.3-times higher risk of celiac disease (P = 1.55 x 10(-5)). This result is suggestive of a primary impairment of the intestinal barrier in the etiology of celiac disease, which may explain why immunogenic gluten peptides are able to pass through the epithelial barrier.

Undiagnosed silent coeliac disease: A risk for underachievement?

Objective. Silent coeliac disease is reported in 1% of Caucasian populations, but there is a lack of knowledge of its natural course and the risk of complications. The need for population screening is debated. We sought for complications of untreated coeliac disease in a well-defined cohort of Finnish adults. Material and methods. Subjects (n=2427, ages 24-39 years) attending the 21-year follow-up visit of the study "Cardiovascular Risk in Young Finns" completed an extensive questionnaire on their health, diet, social situation and family life, and were given a medical examination. Measurement of serum IgA-transglutaminase and IgA-endomysium antibodies identified 21 subjects with silent coeliac disease. Results. The subjects with silent coeliac disease did not differ from the rest of the cohort in age, gender, stature, weight, medical diagnoses (autoimmune, malignant), health concerns, use of alternative medications, physical activity, or in the cause of death their parents. They had lower serum HDL-cholesterol (1.12 versus 1.29 mmol/L; p=0.015), as described for active coeliac disease. Fewer (5.3% versus 22.8%; p=0.047) had a university or college degree or worked in managerial or professional positions (28% versus 45%; p=0.112). Conclusions. The underachievement in education and working life observed in subjects with silent coeliac disease is a new and intriguing finding and may be related to the increased prevalence of depressive and disruptive behavioural disorders described in teenagers with untreated coeliac disease. Our findings add a new ingredient to the ongoing discussion regarding the need for population screening for silent coeliac disease.

Bone mineral density in children with celiac disease. Effect of a Gluten-free diet.

Objective:To assess the degree of osteopenia in children with celiac disease (celiac disease) at the time of diagnosis and the effect of a gluten-free diet (GFD).Design:Longitudinal and prospective study.Subjets:In total, 24 children (18 girls, six boys) diagnosed with celiac disease by means of an intestinal biopsy were included in the study. Mean+/-s.d. age was 4.9+/-4.3 years. In all, 16 patients were under (2.20+/-0.82 year) and eight were over the age of 4 years (10.30+/-2.90 year). The time between the first symptoms and diagnosis was 17.30+/-24.70 months (range: 2-109 months). Spine bone mineral content (BMC), area and bone mineral density (BMD) were measured by DXA at baseline and 1.17+/-0.93 years after GFD.Results:Before treatment, mean+/-s.d. BMD was 0.46+/-0.13 g/cm(2), the BMD Z-score was -1.36+/-1.20, and was below -1 s.d. in 14 patients (58%). BMC, area and BMD increased significantly on GFD. BMD increased from 0.46+/-0.13 to 0.55+/-0.13 g/cm(2) (P<0.001). BMD Z-score improved from -1.36+/-1.20 to -0.23+/-1.20 after GFD. However, BMD increased more than 1 s.d. in 15 of the 16 children under the age of 4 years, a similar increase was only observed in four of the eight children aged more than 4 years, some of whom did not follow GFD strictly. Height and weight increased significantly with GFD (P<0.001) and the increase correlated positively with the increase in BMD.Conclusions:Axial BMD below -1 s.d. was found in 58% of children with celiac disease. Axial bone mass reverted to normal values in most children under the age of 4, who had low bone mass, all of whom followed GFD strictly.European Journal of Clinical Nutrition advance online publication, 30 November 2005; doi:10.1038/sj.ejcn.1602323.

Pregnancy outcome of patients with known celiac disease.

OBJECTIVE: Celiac disease is a permanent intolerance to gluten, probably induced by an autoimmune mechanism. Controversy exists regarding the association between celiac disease and infertility, abortions, intra-uterine growth restriction (IUGR) and stillbirths. The present study was designed to investigate pregnancy outcome of patients with celiac disease. METHODS: A retrospective comparison between all pregnancies of women with and without known celiac disease, delivered during the years 1988-2002, was conducted. RESULTS: During the study period there were 48 deliveries of patients with celiac disease and 143,663 pregnancies of patients without known celiac disease. No statistically significant differences were noted between the groups regarding maternal or perinatal outcomes, including fertility treatments (0% among patients with known celiac versus 2.5% among patients without known celiac sprue; p=0.267), recurrent abortions (0 versus 5.2%; p=0.103), perinatal mortality (2.1 versus 1.4%; p=0.668). However, higher rates of labor induction (29.2 versus 11.9%; p<0.001) and IUGR (6.3 versus 2.1%; p=0.042) were found among patients with celiac disease as compared to patients without known celiac disease. CONCLUSION: The course of pregnancy of patients with celiac disease including perinatal outcomes is favorable. Since we found higher rates of IUGR, careful surveillance should be performed for early detection of IUGR. Further, prospective studies should focus on screening for celiac disease among patients presenting with IUGR of an unknown etiology.

Antagonists and non-toxic variants of the dominant wheat gliadin T-cell epitope in coeliac disease.

BACKGROUND: Coeliac disease (celiac disease) is due to an inappropriate T-cell mediated response to specific gluten peptides. Measured by IFN-g ELISPOT, about half the gliadin-specific T-cells induced with in vivo wheat gluten exposure in HLA-DQ2+ celiac disease are specific for an a/b- gliadin peptide (p57-73 QE65; QLQPFPQPELPYPQPQS) that includes two overlapping T-cell epitopes (PFPQPELPY and PQPELPYPQ). AIM: To define minimally substituted variants of p57-73 QE65 universally devoid of IFN-g stimulatory capacity but capable of antagonising IFN-g secretion from polyclonal T-cells specific for p57-73 QE65. METHODS: Peripheral blood mononuclear cells (PBMC) collected from 75 HLA-DQ2+ celiac disease patients after in vivo gluten challenge were used in overnight ELISPOT assays to screen 218 single or double-substituted variants of p57- 73 QE65 for cytokine stimulatory and antagonist activity. RESULTS: The region p60-71 (PFPQPELPYPQP) and especially p64-67 (PELP) was sensitive to substitution. Twelve substitutions in p64-67 stimulated no IFN-g ELISPOT response. Amongst the 131 partial agonists identified, 45 produced statistically significant inhibition of IFN-g ELISPOT responses when co-cultured in five-fold excess with p57-73 QE65 (n=10). Four substituted variants of p57-73 QE65 were inactive by IFN- g ELISPOT, but consistently antagonised IFN-g ELISPOT responses to p57-73 QE65, and also retained IL-10 stimulatory capacity similar to p57-73 QE65. CONCLUSIONS: Altered peptide ligands of p57-73 QE65 identified using polyclonal T-cells from multiple HLA-DQ2+ celiac disease donors have properties in vitro that suggest a single substitution to certain a/b-gliadins could abolish their capacity to stimulate IFN-g from CD4 T- cells and also have anti-inflammatory or protective effects in HLA-DQ2+ celiac disease.

Effect of breast-feeding on risk of coeliac disease: A systematic review and meta-analysis of observational studies.

BACKGROUND: Coeliac disease (celiac disease) is a disorder that may depend on genetic, immunological, and environmental factors. Recent observational studies suggest that breast-feeding may prevent the development of celiac disease. AIM: To evaluate articles that compared effects of breast-feeding on risk of celiac disease. DESIGN: Systematic review and meta-analysis of observational studies published between 1966 and June 2004 that examined the association between breast- feeding and the development of celiac disease. RESULTS: Six case-control studies met the inclusion criteria. With the exception of one small study, all the included studies found an association between increasing duration of breast-feeding and decreased risk of developing celiac disease. Meta-analysis showed that the risk of celiac disease was significantly reduced in infants who were breast-feeding at the time of gluten introduction (pooled odds ratio 0.48, 95% CI 0.40 to 0.59) compared with infants who were not breast-feeding during this period. CONCLUSIONS: Breast-feeding may offer protection against the development of celiac disease. Breast-feeding during the introduction of dietary gluten, and increasing duration of breast-feeding were associated with reduced risk of developing celiac disease. It is, however, not clear from the primary studies whether breast-feeding delays the onset of symptoms or provides a permanent protection against the disease. Long- term prospective cohort studies are required to investigate further the relationship between breast-feeding and celiac disease.

Anti-tissue transglutaminase antibodies in patients with abnormal liver tests: is it always coeliac disease?

BACKGROUND: Coeliac disease (celiac disease) is found in 5-10% of patients with chronically abnormal liver tests and no obvious cause of liver disease. In this population the efficacy of screening for celiac disease by anti-tissue transglutaminase (anti-tTG) may be impaired by the high rate of positive anti-tTG found in chronic liver disease. AIMS: To evaluate the prevalence of coeliac disease and the role of anti-tTG in patients with non-viral, non-autoimmune chronic and no obvious cause of liver damage. METHODS: Out of 2,512 consecutive patients with abnormal liver tests, 168 (118 men, 50 women; mean age 40.7 +/- 12.6 years) were defined, on the basis of clinical data and liver biopsy, as NAFLD or cryptogenic chronic hepatitis. All were tested by recombinant IgA and IgG anti-tissue transglutaminase. Patients with a positive serology underwent endoscopy with duodenal biopsies. RESULTS: NAFLD was diagnosed in 121 patients, in 6 associated with cirrhosis, while 47 patients were considered as cryptogenic hepatitis in the absence of steatosis. Anti-tTG were positive in 20/168 patients (3 IgA alone; 11 IgG alone; 6 both IgA and IgG). Coeliac disease was found at endoscopy and confirmed by histopathology only in the 6 patients (3.6%) with both IgA and IgG anti-tTG positivity. Four of the patients with celiac disease had NAFLD (3.3%), in 2 of them associated with cirrhosis; while 2 of those with cryptogenic hepatitis (4.2%) had celiac disease. CONCLUSIONS: The prevalence of celiac disease in patients with chronically abnormal liver tests of unexplained etiology is 4%, with no relation with the degree of liver steatosis. Screening should be done by testing for IgA and IgG antibodies and then evaluating by endoscopy and biopsy only patients positive for both.

The effects of atorvastatin on gluten-induced intestinal T cell responses in coeliac disease.

Various experimental models suggest that the cholesterol-lowering drugs statins may also modulate immune responses. Cellular level studies on human disorders are needed, however, to provide a rational basis for clinical testing of statins as immune therapy. Coeliac disease, a chronic small intestinal inflammation driven by HLA-DQ2 restricted mucosal T cells that are specific for ingested wheat gluten peptides, is in many ways ideal for this purpose. In addition, there is a need for alternative treatment to the gluten-free diet in this disorder. Here we have assessed the effects of atorvastatin on gluten-reactive T cells, dendritic cells and the coeliac mucosa by in vitro culture of biopsies. Atorvastatin inhibited gluten-induced proliferation and specific cytokine production of human intestinal gluten-reactive T cell clones and lines. Dendritic cells exposed to atorvastatin displayed a reduced expression of the costimulatory molecule CD83 upon maturation with lipopolysaccharide. Incubation of intestinal biopsy specimens with atorvastatin in vitro, however, did not influence gluten-induced cytokine release. In conclusion, atorvastatin has specific effects on isolated gluten-reactive T cells and dendritic cells, but does not shut down the gluten-induced production of proinflammatory cytokines in intestinal biopsies.

Unexpected role of surface transglutaminase type II in celiac disease.

BACKGROUND & AIMS: In celiac disease (celiac disease), transglutaminase type II (TG2) has 2 fundamental roles: (1) as the autoantigen recognized by highly specific autoantibodies and (2) the modifier of pathogenic gliadin T-cell epitopes. It follows that inhibition of TG2 might represent an attractive strategy to curb the toxic action of gliadin. Here we studied the validity of this strategy using the organ culture approach. METHODS: Duodenal biopsy specimens from 30 treated patients with celiac disease, 33 untreated patients with celiac disease, and 24 controls were cultured with or without gliadin peptides p31-43, palpha-9, and deamidated palpha-9 for 20 minutes, 3 hours, and 24 hours. In 31 patients with celiac disease and 16 controls, TG2 inhibitor R283 or anti-TG CUB 7402 or anti-surface TG2 (6B9) mAbs were used in cultures. T84 cells were also cultured with or without peptides with or without TG inhibitors. Mucosal modifications after culture were assessed by immunofluorescence, in situ detection of TG activity, confocal microscopy, and fluorescence-activated cell sorter analysis. RESULTS: The enzymatic inhibition of TG2 only controlled gliadin-specific T-cell activation. The binding of surface TG2 contained gliadin-specific T-cell activation and p31-43-induced actin rearrangement, epithelial phosphorylation, and apoptosis, both in organ cultures and T84 cells. CONCLUSIONS: These data indicate a novel and unexpected biological role for surface TG2 in the pathogenesis of celiac disease suggesting a third role for TG2 in celiac disease. These results have a specific impact for celiac disease, with wider implications indicating a novel biologic function of TG2 with possible repercussions in other diseases.

Different profiles of wheat antigens are recognised by patients suffering from coeliac disease and IgE-mediated food allergy.

BACKGROUND: Dietary intake of wheat can cause two distinct immunologically mediated diseases with severe gastrointestinal manifestations, coeliac disease (celiac disease) and IgE-mediated food allergy. The pathomechanisms underlying these diseases are different, but the profile of the target antigens in wheat has not been compared for the two diseases. METHODS: We compared IgA- and IgE-reactive antigens in wheat using sera from patients with coeliac disease (n = 35) and food allergy to wheat (n = 16) by one- and two-dimensional immunoblotting. Furthermore, the IgG subclass (IgG1-IgG4) reactivity to wheat antigens was studied by enzyme-linked immunosorbent assay. RESULTS: IgA antibodies from celiac disease patients and IgE antibodies from allergic patients recognised distinct profiles of wheat antigens. Furthermore, the IgG subclass responses to wheat antigens were different in celiac disease and wheat-allergic patients. CONCLUSION: This study thus demonstrates that wheat contains antigens/epitopes which are preferentially recognised by celiac disease patients, whereas others elicit IgE-mediated food allergy. This finding suggests that the nature of a food antigen may influence the quality of the pathological immune response in the gut and has implications for the diagnosis and therapy of hypersensitivity to wheat.

Ataxia, peripheral neuropathy, and anti-gliadin antibody. Guilt by association?

Some authors contend that patients with idiopathic neurological disease who are also anti-gliadin antibody seropositive are gluten sensitive. However, anti-gliadin antibodies lack disease specificity being found in 10% of healthy blood donors. We report a study comparing anti-gliadin antibody with other food antibodies in patients with idiopathic ataxia (20), hereditary ataxias (seven), or idiopathic peripheral neuropathy (32). Patients were HLA typed. IgA anti-tissue transglutaminase antibodies (tTG) were measured. No case was positive for IgA anti-tTG making occult coeliac disease unlikely. HLA DQ2 and HLA DQ8 were found distributed equally across all patient groups and unrelated to gliadin antibody status. HLA DQ2 expressing, anti-gliadin antibody positive cases (so called "gluten ataxia") were rare in our clinics (four cases in 2 years from a population of 2 million). We conclude that coeliac disease per se is not commonly associated with either idiopathic ataxia or idiopathic peripheral neuropathy. Our study also casts doubt on the nosological status of "gluten ataxia" as a discreet disease entity. All food antibodies tested, particularly IgG, were a common finding in both ataxia and peripheral neuropathy groups. No particular food antibody was associated with any patient group. Food antibodies were equally common in hereditary ataxias. We conclude they are a non-specific finding.

Celiac disease in type 1 diabetes mellitus in a North American community: prevalence, serologic screening, and clinical features.

OBJECTIVES: To estimate the prevalence of cellac disease (celiac disease) in pediatric and adult type 1 diabetes melitus in a defined population and to describe clinical features and HLA class II genotypes predictive of celiac disease in screened patients with type 1 diabetes. PATIENTS AND METHODS: All residents of Olmsted County, Minnesota, with type 1 diabetes mellitus on the prevalence date January 1, 2001, were identified with the use of an established medical records linkage system (Rochester Epidemiology Project) and defined clinical criteria. Consenting patients underwent serologic screening with endomyslal antibody and tissue transglutaminase antibody testing and Intestinal biopsies to confirm the diagnosis of celiac disease. A subset of screened patients also underwent HLA class II genotyping. Quality-of-life screening (Medical Outcomes Study 36-Item Short-Form Health Survey) was completed in a subset of patients at the time of serologic screening. RESULTS: Overall, 392 Olmsted County residents with type 1 diabetes on January 1, 2001, were Identified. A total of 158 patients with type 1 diabetes were tested, representing 40% (158/392) of the enumerated diabetic population, and 11 had biopsy-proven celiac disease for an estimated point prevalence of 7.0% (95% confidence Interval, 3.5%-12.1%). Most celiac disease-positive diabetic patients were asymptomatic and expressed an at-risk celiac disease haplotype with at least one of but not both HLA DQ2 or DQ8. CONCLUSIONS: Celiac disease Is not rare In North American patients with type 1 diabetes, and most celiac disease-positive diabetic patients are asymptomatic Irrespective of age at screening.

Enzyme therapy for management of coeliac disease.

Objective. Enzyme therapy based on animal digestive extracts was investigated as a means of completely digesting toxic residues from gluten in the small intestine, thus providing a means of protection of the mucosa. Material and methods. A randomized, placebo-controlled, clinical trial of an encapsulated enzyme extract was conducted in 21 coeliac patients in remission who were challenged with a modest amount of gluten daily over 2 weeks. Enzyme extract (900 mg) in three divided doses was administered during this challenge to half the group and a placebo to the other half in a double-blind, crossover design. Symptoms were recorded in daily diaries; blood was taken for tissue transglutaminase antibodies (anti-tTG) at the start and at intervals up to 12 weeks. Duodenal biopsies were performed for histological assessment at the start and end of each challenge period for 6 patients chosen at random from volunteers. After a further 10 weeks, the groups were changed over, and the same assessments carried out. Results. Only 8 of the 21 patients (38%) had more than 5 episodes of moderate to severe symptoms during either of the gluten challenge periods, and in these, symptoms scores were ameliorated during enzyme therapy compared with the placebo period (p<0.02). Rises of 5 U/ml or more in anti-tTG occurred in only 5 patients at about 6-8 weeks after challenge, but were not correlated with symptoms. Conclusions. Only 1 of the 6 patients had normal histology at entry, thus focusing attention on the need for better management of the disease. By histological criteria, enzyme therapy offered better protection than placebo during the gluten challenges. The study supports the use of enzyme supplementation as a safeguard for patients with coeliac disease because of the difficulty of ensuring a strictly gluten-free diet.

Nasal septal perforation in a patient with subclinical celiac disease: a possible new association.

A female patient presented with nasal septal perforation that did not respond to conventional therapeutic management. Later, because of a malabsorption problem in one of her children, she underwent analytic tests and distal duodenal biopsy, which revealed that she was suffering from subclinical/silent celiac disease. The treatment, a gluten-free diet, unexpectedly resulted in the cessation of the destructive nasal process. Four years later, the patient remains asymptomatic. Nasal septal perforation might constitute a new entity associated with celiac disease hitherto not described in the literature.

Haplotypes in the CTLA4 region are associated with coeliac disease in the Irish population.

Chromosomal region 2q33 encodes the immune regulatory genes, CTLA4, ICOS and CD28, which are involved in regulation of T-cell activity and has been studied as a candidate gene locus in autoimmune diseases, including coeliac disease (celiac disease). We have investigated whether an association exists between this region and celiac disease in the Irish population using a comprehensive analysis for genetic variation. Using a haplotype-tagging approach, this gene cluster was investigated for disease association in a case-control study comprising 394 celiac disease patients and 421 ethnically matched healthy controls. Several SNPs, including CTLA4_CT60, showed association with disease; however, after correction for multiple-testing, CTLA4-658C/T was the only polymorphism found to show significant association with disease when allele, genotype, or carrier status frequency were analysed (carrier status (Allele C), P=0.0016). Haplotype analysis revealed a haplotype incorporating the CD28/CTLA4 and two 5' ICOS polymorphisms to be significantly associated with disease (patients 24.1%; controls 31.5%; P=0.035), as was a shorter haplotype composed of the CTLA4 markers only (30.9 vs 34.9%; P=0.042). The extended haplotype incorporating CD28/CTLA4 and 5' ICOS is more strongly associated with disease than haplotypes of individual genes. This suggests a causal variant associated with this haplotype may be associated with disease in this population.Genes and Immunity advance online publication, 20 October 2005; doi:10.1038/sj.gene.6364265.

Serological testing for celiac disease in women undergoing assisted reproduction techniques.

BACKGROUND: The assertion of a causal relationship between celiac disease and infertility is suggested by several lines of research. Nevertheless, robust evidence has not yet been provided. The present study evaluated, for the first time, the prevalence of celiac disease in women undergoing assisted reproduction techniques (ART). METHODS: Serum samples from 200 Italian women undergoing ART were evaluated for celiac disease by endomisium antibody (EMA) and transglutaminase antibody (t-TGA)--two highly sensitive and specific serological markers. Two hundred women not reporting reproductive problems and having delivered at least one child served as controls. In cases of positive serology, the diagnosis was confirmed by jejunal biopsy. RESULTS: Five (2.5%) women from the study group and two (1.0%) from the control group were found to have celiac disease (P = 0.44). The main indications for ART in women found to have celiac disease were tubal factor in two cases and male infertility in three cases. None of these women reported major gastrointestinal complaints. Extra intestinal signs linked to celiac disease were noted in four out of five patients. CONCLUSION: This study raises the issue of celiac disease screening in ART programmes. Given the available evidence in the literature combined with our observations from this study, the value of serological testing for celiac disease in infertile women remains uncertain. Further studies to address this issue are required.

Clinical, HLA, and small bowel immunohistochemical features of children with positive serum antiendomysium antibodies and architecturally normal small intestinal mucosa.

BACKGROUND: Antiendomysium antibodies have a high sensitivity and specificity for celiac disease. A small percentage of subjects positive for these antibodies have a small intestinal mucosa hitherto considered normal. OBJECTIVES: The aim of this study was to characterize the clinical, serological, immunogenetic, and immunohistological features of these subjects. METHODS: From 409 patients who were positive for celiac-related antibodies, we selected 24 (5.9%) patients who had an architecturally normal small intestinal mucosa. One hundred age-matched celiac patients with a "flat" small intestinal mucosa, and 50 age-matched nonceliac children were also studied. The number of CD3+ and gammadelta+ intraepithelial lymphocytes and of CD25+ lamina propria mononuclear cells, and the expression of crypt HLA-DR and lamina propria ICAM-1 were assessed. HLA haplotyping was also performed. RESULTS: Eleven (45.8%) of the 24 patients had a distinct infiltrative pattern, i.e., an increase in CD3+ intraepithelial lymphocytes (> 2SD of the nonceliac group), whereas 17 (70.8%) had a higher density of intraepithelial gammadelta+ cells. In 17 (70.8%) patients, the number of lamina propria CD25+ cells was increased and/or the expression of ICAM-1 and crypt HLA-DR was enhanced. All 24 patients carried the celiac disease-associated HLA haplotypes. Two of the six patients who remained on a normal diet and underwent a second jejunal biopsy developed villous atrophy. CONCLUSIONS: Most of the patients with serum antiendomysium antibodies and normal jejunal histology showed immunohistochemical signs of immune activation in the epithelium, lamina propria, and crypts. We recommend that such patients be monitored to assess their progress and to determine whether they need a gluten-free diet.

Small-fiber neuropathy/neuronopathy associated with celiac disease: skin biopsy findings.

BACKGROUND: Celiac disease (celiac disease) is increasingly recognized in North America and is associated with a peripheral neuropathy. OBJECTIVE: To report the clinical characteristics and skin biopsy results in patients with celiac disease and small-fiber neuropathy symptoms. DESIGN: Case series. SETTING: Academic peripheral neuropathy clinic. PATIENTS: Eight patients with celiac disease and neuropathy symptoms.Intervention Three-millimeter punch biopsy using the panaxonal marker protein gene product 9.5 to assess epidermal nerve fiber (ENF) density and a gluten-free diet. MAIN OUTCOME MEASURE: Clinical data and ENF density. RESULTS: All patients had asymmetric numbness and paresthesias. Three had more prominent involvement of hands than feet, and 3 had facial numbness. Celiac disease was diagnosed in 5 after their neuropathy began. The following serum antibody levels were elevated: tissue transglutaminase (n = 6), IgA gliadin (n = 4), and IgG gliadin (n = 7). Results of nerve conduction studies were normal in 7 patients. One patient had mildly reduced sural amplitudes. The ENF density was reduced in 5 patients. The ENF density was at the low limit of the normal range in 3 additional patients, 2 of whom had morphologic changes in axons. Three patients had decreased ENF density at the thigh or forearm, which was more severe than at the distal leg, compatible with a non-length-dependent process. Four reported improvement with a gluten-free diet. One had no improvement after 4 months. Symptoms developed in 2 while receiving a gluten-free diet. CONCLUSIONS: Patients with celiac disease may have a neuropathy involving small fibers, demonstrated by results of skin biopsy. The pattern of symptoms, with frequent facial involvement and a non-length-dependent pattern on skin biopsy findings, suggests a sensory ganglionopathy or an immune-mediated neuropathy. Improvement of symptoms in some patients after initiating a gluten-free diet warrants further study.

TNFalpha, IFNgamma and IL-10 gene polymorphisms in a sample of Sicilian patients with coeliac disease.

BACKGROUND: Coeliac disease is associated with DQ2 and DQ8 alleles, but other genes also confer an additional genetic risk. AIMS: Defining whether the genetic profiles of interleukin-10, tumour necrosis factor alpha and interferon gamma are associated with an increased coeliac disease risk. PATIENTS AND METHODS: The functionally gene polymorphisms of tumour necrosis factor alpha (-308G/A), interferon gamma (+874T/A) and interleukin-10 (-1082G/A) were typed using sequence specific primer-polymerase chain reaction in 110 Sicilian coeliac disease patients and in 220 Sicilian healthy controls. RESULTS: No differences in genotype frequencies of interleukin-10 polymorphisms were found between coeliac disease patients and healthy controls. A significant increase of -308A (p<0.033; OR: 1.72; CI: 1.27-2.33) and of +874T (p: 0.0045; OR: 3.02; CI: 1.47-6.21) allele frequencies, both in hetero- and homozygosis, was observed in coeliac patients in comparison with healthy controls. In addition, simultaneous significant higher percentages of -308A and +874T alleles (p: 0.0066; OR: 2.33; CI: 1.42-3.82) as well as simultaneous significant lower percentages of -308A and +874T alleles (p: 0.003; OR: 0.23; CI: 0.10-0.60) were observed in coeliac patients compared with healthy controls. CONCLUSIONS: Genetically determined higher frequencies of -308A tumour necrosis factor alpha and +874T interferon gamma alleles, both in hetero and in homozygosis and mostly whether simultaneous, may play a role in predisposing to gluten intolerance. Subjects positive for -308A tumour necrosis factor alpha and +874T interferon gamma alleles have an increased risk for coeliac disease.

Should patients with coeliac disease have their bone mineral density measured?

BACKGROUND: In 1998 we published guidelines for managing osteoporosis in coeliac disease. These guidelines recommended bone mineral density (BMD) measurement at diagnosis. We analyse the results of following these guidelines in a district general hospital with a view to rationalizing screening. PATIENTS AND METHODS: Forty-three consecutive patients with newly diagnosed coeliac disease had dual-energy X-ray absorptiometry scans of the hip and lumbar spine. Results were correlated with factors that were suspected to influence BMD and were compared with comparable published studies. RESULTS: Osteoporosis at the hip and spine was found in only 7% and 14% of patients, respectively. Mean z scores were not significantly reduced. BMD did not correlate with the duration of gluten exposure, symptoms, degree of villous atrophy, or smoking. At the hip, but not at the spine, there was a significant correlation between BMD and the body mass index. CONCLUSIONS: The surprisingly low yield of reduced BMD, together with doubt about increased fracture rates in coeliac patients, does not support the current recommendations for screening BMD at diagnosis, and the guidelines should be changed.

Serum nitric oxide levels in children with celiac disease.

OBJECTIVES: To determine serum nitric oxide levels in pediatric patients with celiac disease and to compare them with the results obtained after 1 year of gluten-free diet. METHODS: We studied serum nitric oxide levels in 41 newly diagnosed patients with celiac disease. Serum levels of nitric oxide were reevaluated after 1 year of gluten-free diet in 23 of them. Mean age was 10.4 +/- 3.4 years (range 2-17 years). RESULTS: The levels of nitric oxide in pretreatment 41 patients with celiac disease and healthy children were detected as 198.33 +/- 20.22 micromol/L and 135.63 +/- 21.17 micromol/L, respectively (P = 0.0001). Serum nitric oxide level, measured in the blood samples 1 year after gluten-free diet, was 148.27 +/- 27.25 micromol/L (P = 0.001). Serum nitric oxide levels were statistically correlated with the degree of histologic changes in celiac disease. In the patients with celiac disease, pretreatment level of nitric oxide was not correlated with the levels of triglyceride, cholesterol, albumin, aspartate aminotransferase, alanine aminotransferase, or creatine kinase. We found correlations with the level of nitric oxide and Hb, mean corpuscular volume, and ferritin. CONCLUSION: Higher serum nitric oxide levels found in children who had not compliance with gluten-free diet suggested the role of serum nitric oxide as an indicator of diet compliance. Because determination of serum nitric oxide is a simple, rapid, cheap, noninvasive, and highly sensitive method for celiac disease, we think that this parameter can be used in the evaluation of diet compliance in children with celiac disease or even instead of gluten challenge, due to more noninvasive property.

If you made it this far, you're a star! :-) Hope it was interesting for ya!

Share this post

Link to post
Share on other sites

Thanks Tiffany! This will keep me busy for a while! I'm new to all the research and Celiac lingo, but am wanting to learn more. I don't have the time to look all this up, so I appreciate you posting it.


Share this post

Link to post
Share on other sites

Very nice Tiffany!!

Thanks so much for taking the time to put all that info up! :)

- Michelle :wub:

Share this post

Link to post
Share on other sites

Join the conversation

You can post now and register later. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.

Reply to this topic...

×   Pasted as rich text.   Paste as plain text instead

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.

  • Top Posters +

  • Upcoming Events

    • April 17, 2019 Until April 27, 2019
      April 17-27, 2020   For the past few years many of you have asked us to arrange a River Boat Cruise that will allow us to visit Amsterdam's famous Keukenhof Gardens at its prime time of the blossoming of the millions of Tulips and Hyacinths - alongside the windmills of the Netherlands.  With the participation of a minimum of 20 persons we have arranged an All-Inclusive Cruise from Antwerp to Amsterdam.  This cruise will not be offered to the public until January, 2019 and always sells out quickly.   THERE WILL BE NO MONEY REQUIRED NOR COMMITMENT FROM YOU until we have all the final costs and details.  If you are at all interested check out our website for as many of the details that we have as of this time.   We need your request to be placed on a list of interested participants so we can present that number to Uniworld to show we have the sincere interest in this All-Inclusive Bob & Ruth's Gluten-free Cruise.   PLEASE CHECK OUT OUR WEBSITE FOR THE DETAILED INFORMATION THAT WE HAVE AS OF THIS TIME.   http://bobandruths.com
    • April 24, 2019 04:00 PM Until 08:00 AM
      Celiac Emotional Healing Support Group
      Again you are invited to join Johnny Patout, LCSW for Baton Rouge's first emotional healing support group meeting to assist those living with celiac disease manage the emotional challenges so many of us face. Most often the emotional disturbances include depression, disinterest in normal activities, insomnia, grief, mood changes, anxiety, inability to concentrate, extreme concern about managing a gluten-free lifestyle and other emotional and behavioral challenges.
      The professionals at Jamestown Avenue Counseling Center created the emotional healing support group to give us a safe place to begin to process our emotions and support each other as we heal emotionally while managing celiac disease and the resulting autoimmune disorders.
      The emotional healing support group meets every Thursday, 6:00-7:00pm, at the Jamestown Avenue Counseling Center of Baton Rouge. Jamestown Avenue Counseling Center is located at 4637 Jamestown Avenue, Baton Rouge, Suite B-1. Suite B-1 is upstairs.
      The support group is free and open everyone managing celiac disease. For more information: emotionalhealingforceliacs@hotmail.com
    • May 04, 2019 Until May 05, 2019
      Nourished Festival is a family-friendly event with 10 locations across the US. Attendees will be able to sample food, health and beauty products, meet with companies, learn about the most current food lifestyles, receive coupons and attend educational sessions with industry experts. 
      Nourished Festival, managed by The Nourished Group and presented by Enjoy Life Foods, is the largest gluten-free, allergy-friendly and specialty diet event in the US, with 10 locations including.
      Managed by The Nourished Group, formerly The Gluten Free Media Group, The Nourished Festivals are the largest and fastest growing special diet consumer events in the United States. Started in 2007, the events have expanded from one to ten cities throughout the country. The festivals cater to anyone looking to lead a healthier lifestyle or those who follow a specialty diet due to autoimmune conditions, food sensitivities, allergies or intolerances. Offerings including Paleo, Keto, Plant-Based, Gluten-Free, Allergen-Friendly and Nut-Free products. The events provide the opportunity for attendees to sample and purchase new products, receive coupons, meet with brand ambassadors and attend educational classes with industry experts. For more information, visit http://www.nourishedfestival.com 
  • Create New...