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Hyperamylasemia due to macroamylasemia in adult gluten enteropathy.

We report hyperamylasemia due to macroamylasemia in a 33-year-old-woman with gluten enteropathy. Macroamylasemia was demonstrated by precipitation of 97% of amylase activity with PEG 6000. It was associated with increased serum IgA, with elevated values of specific IgA antibodies against alpha-gliadin and with a high titre of IgA anti-endomysium antibodies. Macroamylasemia disappeared after 2 months of a strict gluten-free diet. These data suggest that the increased IgA concentration in adult gluten enteropathy led to increased macroamylase formation.

Adult↗

[Reappearance of alopecia areata in a coeliac patient during an unintentional challenge with gluten].

A patient with coeliac disease presenting alopecia areas as the only symptom is described. Alopecia disappeared completely after a few months of strict gluten free diet and reappeared after an unintentional prolonged introduction of gluten. After a severe gluten free diet, a new and persistent hair growth in the alopecia areas was observed. The possibility a direct relationship in some cases, between coeliac disease and alopecia areata is confirmed.

English Abstract↗

Celiac disease serology in dermatitis herpetiformis. Which is the best option for detecting gluten sensitivity?

BACKGROUND: Dermatitis herpetiformis (DH), a well-established gluten-sensitive skin disorder presenting variable degrees of enteropathy, constitutes a very useful model in order to assess the utility of the celiac disease (CD)-related serology in patients with mild intestinal damage. OBJECTIVE: Our aim was to explore comparatively the performance of a panel of CD-related serologic tests in patients with DH. METHODS: We assessed a series of 18 consecutive patients with skin biopsy proven DH presenting the overall spectrum of intestinal damage ranging from normal mucosa (n = 6) to total villous atrophy (TVA) (n = 6) through partial villous atrophy (PVA) (n = 6). Sera were obtained from all patients while consuming a gluten containing diet. Serologic tests were antiendomysial, anti-tissue transglutaminase and antigliadin antibodies, and newly developed tests detecting both antibody isotypes (IgA and IgG) against deamidated synthetic gliadin-derived peptides (a-GDP). RESULTS: Serologic tests had a variable behaviour depending on the degree of enteropathy. While the majority of tests detected patients with TVA, only 50% of those with normal histology had positive assays. Patients with PVA had discordant results. Classical CD-specific tests were positive in only some patients with mild damage while all of them were identifed by a single assay detecting both isotypes of a-GDR CONCLUSION: The detection of a-GDP antibodies was the most reliable tool in order to identify gluten sensitivity in DH patients presenting a wide range of intestinal damage. Further studies should explore if these findings can be extrapolated to patients with CD having mild enteropathy.

Adolescent↗

[Difficulties of diagnosing gluten enteropathies in adults].

Seven cases of adult patients with gluten enteropathy (1 male and 6 female patients, including 1 patient with Duhring's disease) are presented. These patients suffered from diarrhoea lasting for 1-10 years prior to the diagnosis of gluten enteropathy. Transient diarrhoea was noted in one female patient in her childhood. Blood calcium levels were lowered in all patients and were accompanied by tetany in five and osteomalacia in two patients. One patient's sister is suffering from mucoviscidosis. Earlier, coeliac disease was not diagnosed in any patient. Previous diagnoses included enteritis, hypoparathyroidism or neuro- and myopathies of unknown etiology. The authors suggest that the difficulties in diagnosing gluten enteropathies in adults are due to the lack of biopsy capsules, low acquaintance of physicians with this disease, and indications to small intestine biopsy.

Adult↗

Quantitative estimation of cellular infiltration of the small intestinal mucosa in children with cow's milk and gluten intolerance.

Quantitative estimation of the infiltration by intraepithelial lymphocytes and eosinophils of the mucosa was carried out in 21 children with cow's milk and 35 children with gluten intolerance. Before dietary treatment, a statistically significant increase in the infiltration by LIE in children with milk intolerance to the mean value of 34.1 cells and in children with gluten intolerance to 39.0 cells was found, what statistically significantly differed from the mean value of LIE for the control group (19.0 cells/100 epithelial cells). The eosinophilic infiltration in this phase of the disease was noted in 38% of children with cow's milk intolerance (16.9 cells/mm2) and in 27% of children with gluten intolerance (28.6 cells/mm2). After 8-24 months of elimination diets--a decrease in the mean value of the LIE infiltration in the mucosa was revealed in both treated groups.

Celiac Disease↗

[Parallel morphological, enzyme and immunological research on the jejunal mucosa in patients with gluten enteropathy, chronic nonspecific enteritis and ulcerative colitis].

The results are reported from the study on 120 patients, 30 of them with gluten enteropathy, 50--with chronic unspecified enteritis and 40--with chronic ulcerous colitis. Small intestinal aspiration biopsy was performed to all patients with histomorphological, electron microscopic, enzymatic and immune-fluorescent study. The secretory immunoglobulins in the jejunal juice were studied in 40 patients. Morphological changes, various degrees, were established, that correlate with the increased number of IgG and IgM secretory cells. The exclusion of gluten from the diet in case of gluten enteropathy was followed by normalization of the number and percentage ratio of IgSC and of secretory immunoglobulins. The enzymatic and immune disorders, in chronic unspecific enteritis correlate with the electron microscopic and precede the histologic ones. The role of immune system of small intestine in the etiology and pathogenesis of the various intestinal diseases is discussed.

Adult↗

[Gluten enteropathy--epidemiologic, clinical, morphologic and enzymatic study].

The results from the clinical, morphological and enzymatic studies are reported upon the jejunal mucosa and the effect of a gluten-free diet among a group of 60 patients with gluten enteropathy and 5 patients with idiopathic steatorrhea. The significance of light microscopic and electronmicroscopic studies are discussed in details in making the diagnosis, differential diagnosis and assessment of the results from the treatment of gluten enteropathy.

Adult↗

A long-term study in children with a recognized gluten intolerance.

A retrospective and prospective study was carried out on 54 children with gluten intolerance recognized 5-10 years ago. Coeliac disease (CD) was confirmed in 44 (81.5%) patients. The clinical picture in the observed children showed an evolution during the period of analysis. Intestinal symptoms are rare in adolescence (33%) while they are always present in the youngest children (initial diagnosis). At the time of the follow-up analysis, 67% of the patients demonstrated parenteral symptoms, mainly in the osteoarticular system, CNS, skin, mucous membranes and in only 33% children were the intestinal symptoms present. Over one third of the patients demonstrated body weight and height deficiency, 73% of boys and 39% of girls in age of pubescence had no maturity features. Neurological disorders were present in almost two thirds of the cases and about 5% of the children showed an evident mental retardation. Disruption of the gluten-free diet, frequent dietary errors and ineffective cooperation of the parents are the most probable reasons for physical and mental disturbances in the studied children. The obtained therapeutic results call for the creating of multi-disciplinary active care for children with gluten intolerance.

Adolescent↗

[Gluten enteropathy].

In this case report has been shown 32-old women patient. She was received on Department of Internal medicine of State Hospital "Sarajevo" because of prostration, weight loss (more than 20 kg) and frequently, abundant diarrheas. Clinical treatment, including biopsy of small intestine, referred on gluten-enteropathy. In war-stricken Sarajevo, when major part of food were bread, macaroni and pies, obviously there was perception of sensibility on gluten in this women who hadn't got any similar problem for her life. After adequate diet without gluten, on the control examination two month later, we can hardly recognize our patient. She can get more than 20 kg, without mental depression and would be married soon.

Adult↗

Screening of gluten avenins in foods by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

The first procedure capable of analysing gluten avenins in gluten-free food samples aimed at the diet control of coeliac patients is described. The method is based on the direct observation of the characteristic avenin mass pattern, around 20-30 kDa, as revealed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI/TOF-MS). The mass range where avenin signals appear is free from mass peaks arising from wheat gliadin, barley hordein and rye secalin protein components, which are also toxic to coeliac patients. Therefore, avenins can easily be screened in complex formula food samples elaborated with mixtures of wheat, barley, rye and oats. In addition, a procedure to quantify avenins in food samples is described on the basis of avenin mass area measurement with a detection limit of 0.4 mg of avenins per 100 g of food.

Avena↗

Size and shape of the repetitive domain of high molecular weight wheat gluten proteins. II. Hydrodynamic studies.

This study describes the hydrodynamic properties of the repetitive domain of high molecular weight (HMW) wheat proteins, which complement the small-angle scattering (SANS) experiments performed in the first paper of this series. The sedimentation coefficients, s(0), and diffusion coefficients, D(0), were obtained from the homologous HMW proteins dB1 and dB4 that were cloned from the gluten protein HMW Dx5, and expressed in Escherichia coli. Monodisperse conditions for accurate determination of s(0) and D(0), were obtained by screening a series of buffers using dynamic light scattering. For the first time, hydrodynamic parameters were obtained on monodisperse samples that enabled the determination of the monomeric size and shape. The hydrodynamic values determined on dB1 and dB4 were used to test the worm-like chain (WLC) model that was proposed in the SANS studies. The successful matching of two separately obtained hydrodynamic parameters of dB1 and dB4 using the WLC model provides further evidence for the WLC model. The small discrepancy between the hydrodynamic and scattering data, possibly coming from the excluded volume effect, was compensated by a solvation layer of 1-2 water molecules thick around the protein in the WLC model. The solvation of the central domain is much higher than those of the terminal domains of the HMW subunits. This difference emphasizes the dual role of HMW wheat gluten proteins in water-binding and aggregation.

Biopolymers↗

Size and shape of the repetitive domain of high molecular weight wheat gluten proteins. I. Small-angle neutron scattering.

The solution structure of the central repetitive domain of high molecular weight (HMW) wheat gluten proteins has been investigated for a range of concentrations and temperatures using mainly small-angle neutron scattering. A representative part of the repetitive domain (dB1) was studied as well as an "oligomer" basically consisting of four dB1 units, which has a length similar to the complete central domain. The scattering data over the entire angular range of both proteins are in quantitative agreement with a structural model based on a worm-like chain, a model frequently used in polymer theory. This model describes the "supersecondary structure" of dB1 and dB4 as a semiflexible cylinder with a length of about 235 and 900 A, respectively, and a cross-sectional diameter of about 15 A. The flexibility of both proteins is characterized by a persistence length of about 13 A. Their structures are thus quantitatively identical, which implies that the central HMW domain can be elongated while retaining its structural characteristics. It seems conceivable that the flexible cylinder results from a helical structure, which resembles the beta-spiral observed in earlier studies on gluten proteins and elastin. However, compared to the previously proposed structure of a (stiff) rod, our experiments clearly indicate flexibility of the cylinder.

Biopolymers↗

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↗

Structure characterization of the central repetitive domain of high molecular weight gluten proteins. II. Characterization in solution and in the dry state.

The structure of the central repetitive domain of high molecular weight HMW) wheat gluten proteins was characterized in solution and in the dry state using HMW proteins Bx6 and Bx7 and a subcloned, bacterially expressed part of the repetitive domain of HMW Dx5. Model studies of the HMW consensus peptides PGQGQQ and GYYPTSPQQ formed the basis for the data analysis (van Dijk AA et al., 1997, Protein Sci 6:637-648). In solution, the repetitive domain contained a continuous nonoverlapping series of both type I and type II II beta-turns at positions predicted from the model studies; type II beta-turns occurred at QPGQ and QQGY sequences and type I beta-turns at YPTS and SPQQ. The subcloned part of the HMW Dx5 repetitive domain sometimes migrated as two bands on SDS-PAGE; we present evidence that this may be caused by a single amino acid insertion that disturbs the regular structure of beta-turns. The type I beta-turns are lost when the protein is dried on a solid surface, probably by conversion to type II beta-turns. The homogeneous type II beta-turn distribution is compatible with the formation of a beta-spiral structure, which provides the protein with elastic properties. The beta-turns and thus the beta-spiral are stabilized by hydrogen bonds within and between turns. Reformation of this hydrogen bonding network after, e.g., mechanical disruption may be important for the elastic properties of gluten proteins.

Amino Acid Sequence↗

Comparison of the expression patterns of genes coding for wheat gluten proteins and proteins involved in the secretory pathway in developing caryopses of wheat.

The synthesis of gluten proteins in the developing caryopsis of wheat is highly coordinated, with mRNAs for the various groups being detected from 11 days after anthesis, and the proteins from about 14 days. In contrast, the levels of transcripts for BiP, PDI and PPI are highest at earlier stages of development. The levels of transcripts for two small GTP binding proteins involved in the secretory pathway (Rab1 and Rab5) are also highest early in development, which is consistent with the retention of most of the gluten proteins within the ER to form protein bodies.

Amino Acid Sequence↗

Effects of a gluten-free diet on catch-up growth and height prognosis in coeliac children with growth retardation recognized after the age of 5 years.

The effects of a gluten-free diet on catch-up growth and predicted height were evaluated in 12 children with coeliac disease diagnosed after the age of 5 years and followed for 2-5.5 years. In the majority of the patients, height and bone age were retarded at the time of diagnosis. Under a gluten-free diet growth velocity, age-related height, predicted height and relative bone age increased, height for bone age slightly decreased. In four patients the predicted height remained below the target height, indicating incomplete catch-up growth.

Adolescent↗

Failure to detect specific gluten antigens associated with the immune aggregates in the skin in dermatitis herpetiformis.

The univolved skin of 10 patients with dermatitis herpetiformis (DH) was examined for the presence of gluten antigens with the immunofluorescence technique using a rabbit anti-gliadin antiserum, human antibodies to wheat and to reticulin conjugated to fluorescein-isothiocyanate (FITC) and class-specific anti-human IgA immunoglobulin. In all patients, IgA deposits were found in the tips of the dermal papillae of the uninvolved skin. With the anti-wheat and anti-reticulin conjugates, as well as with the rabbit anti-gliadin antiserum, no specific immunofluorescence was observed in any of the skin specimens. Skin biopsy sections of three DH patients were treated with an acid solution (pH 3.2) in an effort to dissociate antigen-antibody complexes that might be present. After the elution procedure the sections showed undiminished IgA fluorescence, and retesting with the anti-wheat- and anti-reticulin antisera again gave negative results. The skin eluates, two of which contained IgA, had no antibodies to wheat or reticulin. These findings do not give support to the hypothesis that the antigens in the suspected immune complexes in the DH skin consist of gluten.

Animals↗

Natural antibiotic expression in celiac disease--correlation with villous atrophy and response to a gluten-free diet.

As infection influences the pathogenesis and presentation of celiac disease, we investigated the expression of natural antibiotics in this condition. Twenty-three adults were prospectively studied: 10 controls and 13 subjects with untreated celiac disease. Distal duodenal biopsies were taken at baseline and after 6 months of a gluten-free diet and assessed for the expression of natural antibiotics. Epithelial human beta-defensin 1 in subjects with celiac disease had a median of 0.02 unit at baseline, compared with 0.34 unit in controls (P < 0.001). It correlated negatively with the degree of villous atrophy (r = -0.64, P = 0.019) and rose to 0.04 unit on the gluten-free diet (P = 0.035 vs. baseline, P < 0.001 vs. controls). The expression of other antibiotics was unchanged. The expression of epithelial natural antibiotics is limited in celiac disease.

Adult↗