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PubMed1978

Vitamin B-6 absorption in children with acute celiac disease and in control subjects.

The concentration of serum pyridoxal phosphate was determined before and 15, 30, 60, 90, and 120 minutes following an oral load test with 5 mg pyridoxine hydrochloride/kg body weight in 14 children with acute celiac disease and in 15 control subjects. Children with acute celiac disease suffer from a biochemical vitamin B-6 deficiency. The increase in pyridoxal phosphate of children with acute celiac disease after loading was significantly decreased when compared with that of control subjects. In children with celiac disease maximal concentration of serum pyridoxal phosphate appeared later (after 60 minutes) and was decreased in comparison to control subjects (after 30 minutes). A positive correlation existed between the net increase of pyridoxal phosphate 60 minutes following pyridoxine loading and the net increase of blood xylose 60 minutes after oral loading. The results are compatible both with a malabsorption of pyridoxine in childhood celiac disease and a shifting of the site of pyridoxine absorption from the upper part of jejunum into the more distal parts of intestine.

Acute Disease↗
PubMed1998

Circulating oxyntomodulin-like immunoreactivity in healthy children and children with celiac disease.

BACKGROUND: The aim of the study was to evaluate the new hormonal entity oxyntomodulin-like immunoreactivity in malabsorption states, and to assess its potential in celiac disease management. METHODS: We measured basal and postprandial oxyntomodulin-like immunoreactivity values in 35 children divided into 3 groups: group 1 was composed of 13 children with celiac disease, either under a gluten-free diet (8 patients) or normal diet (5 patients); group 2 was composed of 8 children hospitalized for gastroenteritis or chronic diarrhea, without biological evidence of malabsorption nor abnormal jejunal mucosa; group 3 was composed of 22 control subjects. RESULTS: Fasting and meal-stimulated levels in the control group were 71+/-10 and 130+/-26 pmol/l, respectively. Mean concentrations were elevated in patients with celiac disease (basal = 349+/-254 pmol/l, postprandial = 446+/-332 pmol/l) and in the group 2 (basal = 139+/-58 pmol/l, postprandial = 218+/-85 pmol/l), but the difference with control subjects did not reach statistical significance. In children with celiac disease, basal and stimulated values correlated with the degree of malabsorption as assessed by hemoglobin (p = 0.006 and p = 0.01, respectively) and serum folate concentrations (p = 0.03 and p = 0.02, respectively). CONCLUSIONS: Oxyntomodulin-like immunoreactivity is noticeably higher in healthy children than previously measured in healthy adult subjects. This hormonal parameter is not an adequate diagnostic tool in celiac disease. Nevertheless, in the context of celiac disease, its elevation reflects the degree of malabsorption and may provide a quantitative approach of the extent of mucosal damage.

Biomarkers↗
PubMed1996

High frequency of celiac disease in Down syndrome.

We screened 115 children with Down syndrome for celiac disease, using antigliadin, antiendomysium, and antireticulin serum antibodies and an intestinal permeability test. Celiac disease was diagnosed in eight children, giving a frequency of 7.0%. We recommend screening for celiac disease in all persons with Down syndrome, with the use of at least the antiendomysium antibody determination.

Autoantibodies↗
PubMed2006

Serum prevalence of celiac disease in children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: The association between celiac disease and diabetes mellitus has been known for many decades. This combination can be observed in a large proportion of diabetic patients, who are generally asymptomatic. The objective of this study was to evaluate the seroprevalence of celiac disease in children and adolescents with type 1 diabetes mellitus. METHODS: This was a cross-sectional study employing antibody IgA anti-transglutaminase for the serological screening of 354 diabetic children and adolescents treated at pediatric endocrinology clinics in Recife, state of Pernambuco, during the period from January to June 2004. RESULTS: The human anti-transglutaminase test was positive in 37/354 patients, resulting in a seroprevalence of 10.5% (95%CI 7.6-14.2%). Male patients predominated (56.8%) over female patients (43.2%) among those that were seropositive, but without statistical significance. Anti-endomysial antibody testing was performed on patients with positive human anti-transglutaminase results, being negative in 14/37 (37.8%) and positive in 22/37 (59.5%). CONCLUSIONS: The seroprevalence of celiac disease found in diabetic children and adolescents in Pernambuco is elevated, being comparable with levels observed in studies in North America and Europe and lower than in Africa, suggesting that serological screening for celiac disease should be performed for all children and adolescents with type 1 diabetes mellitus.

Adolescent↗
PubMed1985

Celiac disease: does hyposplenism predispose to the development of malignant disease?

Splenic size and function was assessed in eight patients with celiac disease and coexisting malignancy (six had small bowel lymphoma and two gastric adenocarcinoma). The size of the spleen was reduced in four of seven patients as seen at autopsy or radionucleotide scanning. Splenic function was studied using "pitted" erythrocyte counts, platelet counts, and Howell-Jolly bodies and was impaired in five of eight patients. Malignant disease developed in some celiacs with normal splenic size and function. Splenic function as measured by pitted erythrocyte counts was similar in the celiac patients with malignancy and appropriately matched nonmalignant celiacs. We conclude that hyposplenism in celiac disease does not influence the development of malignant disease.

Adenocarcinoma↗
PubMed2007

Celiac disease presenting with motor neuropathy: effect of gluten free-diet.

Celiac disease is a rare cause of neuropathy that most commonly presents with symmetric distal sensory disturbances. We describe two patients with celiac disease in whom neuropathy presented unusually with progressive weakness of the limbs. In both patients a gluten-free diet induced a significant improvement of muscle strength and neurophysiological abnormalities, suggesting a direct pathogenetic role of sensitivity to gluten. Celiac disease should be considered in patients with idiopathic neuropathy even when gastrointestinal symptoms are absent.

Adult↗
PubMed2003

Autoantibodies and histogenesis of celiac disease.

OBJECTIVE: Autoantibodies are used as markers for celiac disease (CD) identifying patients with mucosal lesions. The purpose of this study was to evaluate the sensitivity and role of the autoantibodies such as IgA antiendomysium (EMA), IgA antigliadin (AGA) and the IgA antitissue transglutaminase (tTGA) in histogenesis of celiac disease. METHODS: Seventy-nine cases including 30 untreated celiacs, 5 celiacs on gluten-free diet (GFD), 41 first degree relatives and 3 non-relatives suspected for CD were investigated. Three untreated celiacs with IgA deficiency were excluded from this study group. IgA antibodies to tTGA were determined by ELISA, as described before. Twelve of 41 relatives and 2 cases of non relatives suspected with positive serology underwent a small intestinal biopsy. Results were correlated with the degrees of abnormality of the intestinal mucosa in patients with CD. Intestinal biopsies obtained from study population were evaluated for histological quantification. RESULTS: Celiacs and suspected cases with positive EMA/AGA and or tTGA showed shorter villi (p < 0.007) and/or a higher number of intraepithelial lymphocytes (IEL) (p < 0.035). The sensitivity of serology (EMA, AGA, tTGA) in patients with Marsh IIIc was 100%. However, in patients with Marsh IIIa the sensitivity for EMA, AGA, and tTGA was 40%, 50% and 20% respectively. CONCLUSIONS: The appearance of antibodies is related to the degree of mucosal infiltration by IELs. Although tTGA, like EMA provide a highly sensitive parameter for the detection of celiacs with severe mucosal damage, it appears to be less sensitive (even less than AGA) in celiac patients with milder histopathological abnormalities. However, it should be recognized that the substantial part of the celiac population present with these milder forms of mucosal abnormalities. Using tTGA as a single test in screening may result in missing up to 60-70% of celiacs with mild mucosal abnormalities. Combination with other screening tests (at least with AGA) is essential and strongly recommended

Adolescent↗
PubMed1986

Jejunal fold separation in adult celiac disease: relevance of enteroclysis.

The number of folds in the proximal jejunum was measured retrospectively in 25 studies of patients with adult celiac disease and 75 control subjects. The average number of folds per inch of proximal jejunum in the group with celiac disease was 2.88 (none to five), as against 4.88 (three to seven) in the controls. The difference was less pronounced in the distal ileum. A "mosaic pattern" was demonstrated in three patients. Positive radiologic evidence of celiac disease could be elicited in 76% of the patients' studies. Demonstration of five or more folds in the jejunum and/or three or fewer folds in the ileum would have been evidence against a diagnosis of celiac disease in 67 of the 75 controls. Indications for the use of radiography in celiac disease are reassessed.

Barium↗
PubMed1998

TNF microsatellite alleles a2 and b3 are not primarily associated with celiac disease in the Finnish population.

Recently, an independent association between tumor necrosis factor (TNF) gene polymorphism and celiac disease was observed in the Irish population. We tested this association in Finnish patients with celiac disease. The TNF microsatellite alleles a2 and b3 were strongly associated (Pcorr<0.0001 for both) with celiac disease when the patients were compared to the random population. However, when the comparison was made with the DQ2-matched controls, no association could be found. We therefore conclude that in Finland the TNFa2 and b3 alleles are associated with DQ2-positive haplotypes rather than celiac disease.

Alleles↗
PubMed1994

Celiac disease and insulin-dependent diabetes mellitus. Screening in an adult population.

We screened for celiac disease, by means of IgA class anti-endomysium antibodies (EmA), 383 consecutive adults with insulin-dependent diabetes mellitus (IDDM). Two control populations entered the study as well: 151 adults with biopsy proven celiac disease, as true positives; and 520 controls (healthy and diseased) as true negatives. IgA-EmA positivity was found in 145 of 151 (96%) celiac disease patients but in none of the controls (100% specificity). EmA were positive in 12 of 383 (3.13%) IDDM patients: 10 of these positives underwent intestinal biopsy, which showed either partial or total villous atrophy. Only one patient presented with gastrointestinal complaints, but severe iron deficiency was found in all. The IDDM celiac patients were started on a gluten-free diet: four refused both the diet and the follow-up protocol. Approximately one year after gluten withdrawal no significant change in the degree of diabetes control was observed, while an increased requirement for insulin was observed in three of four patients who strictly complied with the diet. The prevalence of biopsy-proven celiac disease among adult IDDM patients (1:38), eight times higher than that recently estimated for the general Italian population and the absence, except in one case, of gastrointestinal symptoms emphasizes the benefit of screening programs on populations at risk.

Adolescent↗
PubMed1989

Challenge with gliadin induces eosinophil and mast cell activation in the jejunum of patients with celiac disease.

PURPOSE: The aim of this study was to clarify the role of eosinophils and mast cells in the small bowel in celiac disease. PATIENTS AND METHODS: Patients with celiac disease (n = 10) were investigated by perfusion of a closed jejunal segment. The concentrations of certain granule constituents from eosinophils, eosinophil cationic protein (ECP), and from mast cells/basophils, histamine, were measured and the jejunal secretion rates of these cellular markers were calculated. RESULTS: Compared with findings in healthy control subjects (n = 14), increased secretion rates were observed under basal conditions in patients with histopathologically active celiac disease. Gliadin, administered by perfusion to the jejunal segment, induced a fourfold increase in ECP secretion and a twofold increase of histamine secretion in patients with celiac disease (n = 7), but did not influence the secretion rates of these substances in healthy controls (n = 3). The secretion rate of ECP started to increase 20 minutes after challenge of the perfused segment with gliadin and reached maximum levels 40 minutes later. The secretion rate of histamine started to increase 40 minutes after gliadin administration. Concurrently with these inflammatory events, the secretion of albumin was doubled as a sign of increased mucosal leakage. CONCLUSION: These data indicate that eosinophils and mast cells are both involved in the early gliadin-induced reactions of the small intestine, and suggest that these cells are effector cells participating in the celiac lesion of the mucosa.

Adult↗
PubMed1990

Celiac disease is associated with an extended HLA-DR3 haplotype which includes HLA-DPw1.

HLA-DP polymorphism was examined among celiac disease patients and controls. Restriction fragment length polymorphism (RFLP) genotyping showed a significant association of DPw1 in celiac disease (32/80) compared with controls (6/53, p = 0.0002). DPw1 typing by RFLP was verified using DPB1-amplified DNA and an oligonucleotide probe specific for the DPw1-associated DPB1 gene. The RFLP-assigned DPw1 genotype corresponded closely to the binding pattern of the sequence-specific oligonucleotide probe, although discrepancies did occur. The association between celiac disease and DPw1, however, remained. Oligonucleotide probe specificity was confirmed by sequencing DPB1-amplified DNA from four DPw1-genotyped celiacs. DPw1 is only present in celiacs who genotype DR3a-positive. Of DR3a controls 24% are DPw1-positive compared with 5% of non-DR3a controls (p = 0.03), suggesting that an extended DR3a, DPw1 haplotype occurs in the control population. This haplotype forms a large proportion of the DR3a haplotypes predisposing to celiac disease. Alternatively, DPw1 may represent an independent risk factor inherited in linkage with HLA-DR3 and -DQw2. Although predisposition to celiac disease is likely to be mediated by a specific DQ alpha/DQ beta heterodimer, a direct role for the DPw1 antigen cannot be discounted.

Base Sequence↗
PubMed1990

Anti-gliadin antibody panel and xylose absorption test in screening for celiac disease.

We prospectively evaluated the use of a widely used commercially available anti-gliadin antibody (AGA) panel, and compared it with the xylose absorption test in screening pediatric patients with possible celiac disease for small intestinal biopsy. Sixty children were investigated with a 1-h xylose absorption test, IgG and IgA AGA panels, and small bowel biopsy; 15 patients were diagnosed with celiac disease. The xylose was sensitive (93%) but not specific (47%) for celiac disease. The IgA AGA test had high sensitivity (100%) but low specificity (58%), while the IgA AGA test had low sensitivity (53%) but high specificity (93%) in screening for celiac disease. We conclude that the AGA panel currently available in the United States is comparable to, but not significantly different than, the xylose absorption test when used as the only laboratory test in screening for celiac disease. A two-step screening process would have best improved our ability to predict celiac disease. We recommend screening with the AGA panel, and obtaining a xylose test if only the IgG is abnormal. Biopsies should be performed in cases with high IgA AGA, or with abnormal IgG AGA and xylose values. This approach is clinically preferable, does not add cost, and spares children from unnecessary small bowel biopsies.

Absorption↗
PubMed2005

Plasma carnitine ester profile in adult celiac disease patients maintained on long-term gluten free diet.

AIM: To determine the fasting plasma carnitine ester in patients with celiac disease. METHODS: We determined the fasting plasma carnitine ester profile using ESI triple quadrupol mass spectrometry in 33 adult patients with biopsy-confirmed maturity onset celiac disease maintained on long term gluten free diet. RESULTS: The level of free carnitine did not differ as the celiac disease patients were compared with the healthy controls, whereas the acetylcarnitine level was markedly reduced (4.703 +/- 0.205 vs 10.227 +/-0.368 nmol/mL, P<0.01). The level of propionylcarnitine was 61.5%, butyrylcarnitine 56.9%, hexanoylcarnitine 75%, octanoylcarnitine 71.1%, octenoylcarnitine 52.1%, decanoylcarnitine 73.1%, cecenoylcarnitine 58.3%, lauroylcarnitine 61.5%, miristoylcarnitine 66.7%, miristoleylcarnitine 62.5% and oleylcarnitine 81.1% in the celiac disease patients compared to the control values, respectively (P<0.01). CONCLUSION: The marked decrease of circulating acetylcarnitine with 50-80 % decrease of 11 other carnitine esters shows that the carnitine ester metabolism can be influenced even in clinically asymptomatic and well being adult celiac disease patients, and gluten withdrawal alone does not necessarily normalize all elements of the disturbed carnitine homeostasis.

Adult↗
PubMed1997

Heterogeneous reactivity patterns of HLA-DQ-restricted, small intestinal T-cell clones from patients with celiac disease.

BACKGROUND & AIMS: T-cell immune reactions toward wheat gliadins seem important in the pathogenesis of celiac disease. We have previously shown that gliadin-specific T-cell clones (TCCs) from the small intestinal mucosa of patients with celiac disease are predominantly restricted by the celiac disease-associated HLA-DQ2 and HLA-DQ8 molecules, suggesting a link between the HLA association and immunopathogenesis. The aim of the present study was to investigate the nature of the stimulating gliadin antigens. METHODS: Three different pools of gliadins and one purified alpha-type and two purified gamma-type gliadin preparations were prepared by ion exchange chromatography and tested for recognition by a panel of small intestinal gliadin-specific TCCs. RESULTS: Evidence suggested that enzymatic digestion and heating of the gliadins influenced TCC stimulation. Most of the TCCs recognized all three gliadin pools, but some had distinct reactivity patterns. Thirteen of 21 TCCs responded to one or more of the three purified gliadins discerning highly discriminative patterns. CONCLUSIONS: Small intestinal, gliadin-specific T cells from patients with celiac disease show diverse reactivity patterns. Stimulation of large numbers of different gliadin-specific T cells in the small intestinal mucosa of patients with celiac disease may occur; this may be an important immunopathogenic step in the disease.

Celiac Disease↗
PubMed1998

Hepatic sinusoidal dilatation associated to giant lymph node hyperplasia (Castleman's): a new case in a patient with periorbital xanthelasmas and history of celiac disease.

We present a new case of hepatic sinusoidal dilatation associated to giant lymph node hyperplasia or Castleman's disease in a 23-year-old patient with xanthelasmas and history of celiac disease. He presented with weight loss, hepatomegaly, periorbital xanthomas, anemia, accelerated erythrosedimentation rate, hypoalbuminemia, hypergammaglobulinemia at the expense of immunoglobulin G (IgG), high titers of autoantibodies, and increase of serum alkaline phosphatase and gamma glutamyl transpeptidase activity. A liver biopsy showed sinusoidal dilatation. Fifteen months later, a computed axial tomography showed a retroperitoneal tumor that turned out to be a giant lymph node hyperplasia. After resection of the tumor all clinic and biochemical manifestations had faded, suggesting an association between xanthelasmas, Castleman's disease, sinusoidal dilatation, and celiac disease. A humoral factor produced by the lymph tumor of the patient may have been responsible for the immunologic alterations he presented.

Adult↗
PubMed2005

Celiac disease in an adult Turkish population with type 1 diabetes mellitus.

Celiac disease is a frequent cause of morbidity among patients with type 1 diabetes mellitus. In this study our objective was to determine the prevalance of celiac diasease in a Turkish adult population with type 1 diabetes mellitus. Patients included 122 type 1 diabetes cases from adult diabetes clinic. Total IgA and IgA-antiendomysial antibody (AEA) assays were performed. Patients positive for IgA-AEA were asked to undergo small intestinal biopsy. Of the 122 patients, none was IgA deficient and 3 had positive IgA-AEA results (2.45%). All three of these patients had biopsies diagnostic of celiac disease. The body mass index (BMI) values of patients with positive AEA were significantly lower than normal (P = 0.024). Among the gastrointestinal complaints there was an association between early satiety and AEA positivity (P = 0.02). None of the other gastrointestinal complaints or age, duration of diabetes, glycosylated hemoglobin values, or insulin doses used were found to be related to AEA positivity. Celiac disease has a high prevalence among Turkish paients with type 1 diabetes mellitus. Screening for IgA-AEA during routine investigations of type 1 diabetic patients is important to prevent celiac-associated symptoms.

Adult↗
PubMed2001

Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study.

OBJECTIVES: Many afflictions have been associated with celiac disease, but chance associations may exists. The aim of this study was to establish, by means of a multicenter prospective study, the prevalence of thyroid impairment among adult patients with newly diagnosed celiac disease and to evaluate the effect of a 1-yr gluten withdrawal on thyroid function. METHODS: A total of 241 consecutive untreated patients and 212 controls were enrolled. In 128 subjects a thorough assessment, including intestinal biopsy, was repeated within 1 yr of dietary treatment. Thyroid function was assayed by measuring the levels of TSH, free T3, free T4, thyroperoxidase, and thyroid microsome antibodies. RESULTS: Thyroid disease was 3-fold higher in patients than in controls (p < 0.0005). Hypothyroidism, diagnosed in 31 patients (12.9%) and nine controls (4.2%), was subclinical in 29 patients and of nonautoimmune origin in 21. There was no difference regarding hyperthyroidism, whereas autoimmune thyroid disease with euthyroidism was present in 39 patients (16.2%) and eight controls (3.8%). In most patients who strictly followed a 1-yr gluten withdrawal (as confirmed by intestinal mucosa recovery), there was a normalization of subclinical hypothyroidism. Twenty-five percent of patients with euthyroid autoimmune disease shifted toward either a subclinical hyperthyroidism or subclinical hypothyroidism; in these subjects, dietary compliance was poor. In addition, 5.5% of patients whose thyroid function was normal while untreated developed some degree of thyroid dysfunction 1 yr later. CONCLUSIONS: The greater frequency of thyroid disease among celiac disease patients justifies a thyroid functional assessment. In distinct cases, gluten withdrawal may single-handedly reverse the abnormality.

Adult↗