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Gluten intolerance in infants and children: what diagnosis and what recommendations? Gluten intolerance or celiac disease is a relatively common pathology that is still underdiagnosed in pediatrics due to its heterogeneous presentation. Apart from the classic form of malabsorption with diarrhea and growth retardation, pathology should be sought in the event of a family history of celiac disease, autoimmunity and in the context of certain syndromes. Other clinical or laboratory signs should also suggest the diagnosis. Any suspicion should lead to assays for total IgA and anti- transglutaminase IgA. If the child is symptomatic or not, the absence of upper gastrointestinal endoscopy with biopsies is possible to make the diagnosis after agreement of the family, if the levels of anti-transglutaminase IgA are greater than 10 times the upper limit of normal, and if the anti-endomysium IgA, assayed on a second sample, are also positive. Management is based on a strict gluten-free diet.Intolérance au gluten en pédiatrie : diagnostic et recommandations. L’intolérance au gluten, ou maladie coeliaque, est relativement fréquente mais reste sous-diagnostiquée en pédiatrie du fait de sa présentation hétérogène. En dehors du tableau classique de malabsorption, avec diarrhée et retard de croissance, elle doit être recherchée en cas d’antécédents familiaux de maladie coeliaque, d’auto-immunité et dans le cadre de certains syndromes. D’autres signes cliniques ou biologiques doivent également évoquer ce diagnostic. Toute suspicion impose le dosage des IgA totales et des IgA antitransglutaminase. Que l’enfant soit symptomatique ou non, si les taux d’IgA antitransglutaminase sont supérieurs à 10 fois la limite supérieure à la normale, et si les IgA anti-endomysium, dosées sur un deuxième prélèvement, sont également positives, le diagnostic peut être posé sans endoscopie digestive haute avec biopsies, après accord de la famille. La prise en charge repose sur un régime d’éviction strict du gluten à vie.

La maladie cœliaque (MC) est l'une des maladies auto-immunes les plus fréquemment associées au diabète de type 1 (DT1). La prévalence de MC dans DT1 varie de 3 à 6%. La présentation clinique de MC dans DT1 est classé comme asymptomatiques dans environ la moitié des cas. L'objectif de notre étude est de déterminer la fréquence des auto-anticorps anti-transglutaminase tissulaire (AtTG) et anti-gliadines (AAG) chez les patients diabétiques de type 1 dans le but de recommander une éventuelle biopsie jéjunale et d'instaurer un régime sans gluten précocement avant l'installation des signes cliniques et des complications de la maladie cœliaque. Les sujets inclus dans cette étude sont des patients atteints de DT1 non traités pour la MC et qui ne présentent pas de signes en faveur de cette pathologie. La détection des AtTG de classe IgG et IgA et AAG classe IgG et IgA a été réalisée par technologie Luminex. Nous avons inclus 31 patients. Il s'agit de 16 hommes et 15 femmes. Les AAG de classe IgA étaient positifs chez 4(13%) patients et chez 7(22,5%) patients pour les IgG. Les AtTG de classe IgA étaient positifs chez 3(10%) patients et chez une patiente (3%) pour les IgG. Dans notre étude l'association du diabète type 1 et des marqueurs biologiques de la MC n'est pas rare d'où l'intérêt de son dépistage systématique chez des diabétiques de type 1. Le diagnostic de cette forme atypique et silencieuse de la MC est important compte tenu du risque de complications sérieuses à type de malabsorption et de cancers digestifs.

Screening studies using high-sensitivity and specificity markers indicate a prevalence of celiac disease of up to 1% in European and North-American populations. Celiac disease is a frequent condition that has become an important public health issue. Yet the majority of cases remain undiagnosed due to the polymorphism of its clinical manifestations. The new insight in the pathogenesis of celiac disease has lead to the development of new diagnostic tools. Early screening of symptomatic patients and pre-identified at-risk groups significantly improves the quality of life while reducing morbidity and mortality. However, prophylactic benefits of early diagnosis by assessing the general population have not been shown in any study. French and Northern American scientific societies have introduced serological testing in their newly revised strategies to diagnose celiac disease. Older markers judged insufficiently accurate like anti-gliadin and anti-reticulin antibodies have recently been withdrawn from the list of reimbursed medical expenses in France. Anti-endomysium and tissue transglutaminase IgA antibodies have proven to be at this day the most sensitive and specific markers for the diagnosis and follow-up of patients on gluten-free diet, at the exception of IgA-deficient patients. Assays testing for IgG antibodies are recommended upon IgA-deficiency. Although very accurate, a better standardisation of current assays may enable serological testing to replace in a near future histological confirmation brought by small bowel biopsies which remains today the gold standard test to diagnose celiac disease. Indeed, serological testing represents and attractive alternative as it is less invasive, less expansive, laboursaving and more objective in interpretation.

Celiac disease (CD) is a chronic inflammatory enteropathy caused by the ingestion of gluten. A safe and efficient but unpleasant treatment exists for CD in form of a strict gluten-free diet. Thus, there is a need for new treatment strategies, which are based on the improved and advanced understanding of the pathophysiology of CD. The first strategy consists in reducing or even eliminating major antigenic motifs in gluten, responsible for the inflammatory reaction. The use of less immunogenic wheat was suggested but this seems rather difficult to realize. However, a complete digestion of the immunogenic parts of gluten looks very promising. This can be obtained by the use of polymers, capable to sequester gluten proteins or even better via the exogenous administration of propyl-endopeptidases, with two different enzymes under development. Another approach could be the use of inhibitors of tissue transglutaminase, a strategy which is under clinical investigation. Alternatively, inhibition of the site of liaison of immunostimulatory peptides with HLA molecules was suggested and is also under investigation in vivo. For patients suffering from refractory sprue, the inhibition of IL15 might be of therapeutic interest with the hope to improve the fatal outcome of many of these patients. However, the ultimate treatment approach is in form of prevention and the role of infectious agents, such as Rotavirus, in disease onset has to be considered.

Recently, anti-deamidated gliadin antibodies were proposed for the serological diagnosis of celiac disease. We evaluate the specificity of different anti-deamidated gliadin antibodies ELISA in comparison with conventional anti-native gliadin kits. Serum samples from 46 non celiac patients were analyzed by five different quantitative ELISA for anti-native gliadin, anti-deamidated gliadin and anti-transglutaminase neo-epitope antibodies together with a screening ELISA. Twenty-four percent of the patients demonstrated anti-native gliadin IgA and 63% IgG antibodies. Using anti-deamidated gliadin antibodies, the number of false positive IgA and, particularly, IgG results, markedly decreased in the non celiac patients: 21 and 24% respectively with anti-Gliadin (GAF-3X) Euroimmun kit, 7 and 26% with Bindazyme Human Anti-Gliadin (MGP) The Binding Site kit and 0 and 41% with Celiac G+ Immco kit. The new assay which makes use of the physiological complex of tissue transglutaminase cross-linked with deamidated gliadin peptides, called neo-epitope, did not improve the differential diagnosis of celiac disease with 30% of false positive results in IgG (2% in IgA). Using the Inova screening kit, a positive result for IgA and/or IgG anti-deamidated gliadin and/or anti-tissue transglutaminase antibodies was obtained in 24% of the non celiac patients. In conclusion, our study assessed the superiority, in terms of specificity, of anti-deamidated gliadin antibodies, over the conventional anti-gliadin antibodies for the differential diagnosis of celiac disease.

Celiac disease is poorly documented in intertropical Africa. The purpose of this retrospective report was to describe 8 cases observed at the Groupement Medico-Chirurgical of Bouffard Hospital in Djibouti (Horn of Africa) between January 2003 and January 2006. There were 5 females and 3 males ranging in age from 9 months to 17 years old (mean age: 48 months). Six patients were of Somali ethnic origin and two of Yemenite ethnic origin. Six were classified as middle class and 2 as lower class. All forms were symptomatic associating constant loss of weight with digestive manifestations (diarrhoea and vomiting). Diagnosis of celiac disease was based on the presence of anti-gliadin antibodies IgA and IgG associated with anti-endomysium or anti-transglutaminase antibodies that were measured in six and two cases respectively. Gastroduodenal endoscopy performed in three cases including two with duodenal biopsy demonstrated villous atrophy associated with gross of intra-epithelial lymphocytosis. A gluten-free diet initiated in five patients led to clinical improvement in four cases with a follow-up of 8.25 months. The findings of this study in Djibouti show that celiac disease exists in intertropical Africa. Its presentation is quite similar to elsewhere but diagnosis is more difficult due to poor knowledge about the disease and limited diagnostic facilities. Favourable response to presumptive treatment by a gluten-free diet is an alternative for diagnosis especially in Djibouti where eating habits differ from those in industrialized countries and this type of diet is easier to follow.

Celiac disease is associated with a number of extra-gastrointestinal features such as hepatitis, arthralgia, and recurrent foetal loss. However respiratory involvement is an extremely rare disorder. We report a case of celiac disease revealed by bronchiectasia in a 39-year-old man. The patient reported a history of recurrent pulmonary infections and intermittent intestinal symptoms in childhood. Wegner granulomatosis was initially suspected because of rhinopulmonary involvement. Serum's patient was tested for ANCA and anti-tissue antibodies. The latest test was performed on histological sections from rat and revealed the presence of anti-reticulin antibodies. Further testing, for anti-tissue transglutaminase and anti-endomysium antibodies, revealed positive results. Celiac disease was confirmed by histological examination of intestinal biopsy. Pulmonary symptoms were improved on a gluten free diet suggesting a causal relationship between celiac disease and respiratory symptoms.

to evaluate the prevalence of celiac serological markers; anti-transglutaminase (ATGt), anti-endomysium (AE), anti-gliadin (AGD) and anti-reticulin (AR) antibodies; in type 1 diabetic Tunisian adults.261 type 1 diabetic patients aged from 16 to 60 years were enrolled in this prospective study. IgG and IgA transglutaminase and gliadin were measured with ELISA. IgA AE were tested by indirect immunofluorescence using 2 substrates; monkey oesophagus and human umbilical cord. AR were detected by indirect immunofluorescence on rat liver, kidney and stomach. Sera IgA level was measured by turbidimetry.83/261 of diabetics were positive for at least one antibody, 5.7% had ATGt-A, 3.4% AE on monkey esophagus, 3.1% AE on umbilical cordon, 18% AGD-A, 19.5% AGD-G and 3.1% AR. There was an excellent concordance between AE and ATGt (r = 0.9). Out of the 261 diabetics, 5 had an IgA deficiency and one of them has IgG AE and ATGt.serological markers of celiac disease seem to be frequent in diabetics. Nevertheless, diagnosis must be confirmed by histological studies which allow us to know the real prevalence of celiac disease in diabetic adults.

To evaluate the interest of IgA antibodies to tissue transglutaminase in the diagnosis of children coeliac disease compared with anti-endomysium and anti-gliadin antibodies.Seventy children with coeliac disease (mean age: 5 years and 8 months) and 99 disease controls (mean age: 4 years and 5 months). IgA anti-transglutaminase were tested by ELISA using a human recombinant tissue transglutaminase. IgA anti-endomysium were detected by indirect immunofluorescence on monkey oesophagus.The middle rate of IgA anti-transglutaminase was 101.06 units in patients and only 0.47 unit in controls. IgA anti-transglutaminase and IgA anti-endomysium were in agreement in 98.8% of cases; only two cases were discordant (+/- and -/+). Globally, the two markers had the same sensitivity (90%), specificity (98%), negative (93.2%) and positive (96.9%) predictive values. For anti-gliadin antibodies, the IgG were more sensitive (88.6%) and the IgA more specific (93.9%).IgA anti-tissue transglutaminase can be used instead of IgA anti-endomysium as a serological marker of screening and diagnosis of coeliac disease in children after 3 years.

International audience; The aim of this study was to determine the prevalence of celiac disease (CD) markers in a French cohort of 84 children type 1 diabetics. Detection of antitransglutaminase (AtTG), antiendomysium (AEA) and antigliadin (AGA) antibodies was performed. Group 1 included 81 (96.4%) diabetic patients with negative antibodies. Group 2 included 3 patients (3.6%) with positive serological markers: 1 AGA-AEA-AtTG and 1 AEA-AtTG with proved histological diagnosis and 1 AGA positive with negative histology. No statistically significant difference was observed between the groups with regard to age, duration of diabetes, familial target stature, and ratios Height/Age and Weight/Height. Presence of CD serological markers was related to a lower level of HbA1c. Prevalence of CD serological markers is important in this French cohort but lower than other countries.

Coeliac disease is an intolerance to gluten that classically produces a chronic diarrhoea with a picture of malabsorption and a total villous atrophy. These elements regress completely in a sequential way under a prolonged strict gluten-free diet. The progress registered in the understanding of this affection depends on the individualization of the atypical forms (delayed isolated stature, constipation...) of asymptomatic forms thanks to the study of specific antibodies (anti-gliadin, anti-endomysium, and more recently anti-transglutaminase). The auto-immune nature of coeliac disease is well established. The diagnostic criteria are simplified allowing the commencement of a gluten-free diet which must be perfectly detailed. Finally, allergy to wheat flour merits individualization in the framework of coeliac disease (cf. article).

The catabolism of glutathione and glutathion conjugates is initiated by the cleavage of the y-glutamyl moiety by the only enzyme y-glutamyltransferase (GGT E C 3.2.2.2). This heterodimeric glycoprotein arise From the proteolytic cleavage of a precursor and it is localized on the outer face of the plasma membrane. Important variations in GGT activity are known to occur during development, carcinogenesis and cell differentiation. It is commonly admitted that GGT participates in the active transport of aminoacids, but also in other biochemical pathways such as detoxification or inflammatory responses by processing GSH-conjugated electrophiles and leukotrienes. GGT genomic organization is well established in rat and mouse. A unique gene encodes several mRNA species that differ in the il' 5' untranslated regions. These mRNAs are transcribed under the control of several tissue-specific promoters which have been described here., Le catabolisme du glutathion et de ses dérivés débute par le clivage du groupement y-glutamyle par la seule enzyme apte à cette réaction, la gamma-glutamyltransférase (GGT E C 3.2.2.2). Cette glycoprotéine hétérodimérique est issue du clivage protéolytique d'un précurseur et est localisée à la surface externe des membres plasmiques. L'activité de cette enzyme varie fortement au cours du développement, de la cancérogenèse et de la différenciation cellulaire. Il est admis qu'elle participe au transport actif de certains acides aminés ainsi qu'aux processus de détoxication et aux réactions inflammatoires en métabolisant les conjugués électrophiles du glutathion et les leucotriènes. L'organisation génomique de la GGT est bien définie chez le rat ou la souris. Un seul gène murin code pour des ARNm différant uniquement par leurs régions 5' non traduites. Ces ARNm sont sous le contrôle de différents promoteurs d'ores et déjà décrits. [...]

Tetanus (TeNT) neurotoxin and botulinum (BoNT, serotypes A-G) neurotoxins are di-chain bacterial proteins of MW-150 kDa which are also termed as clostridial neurotoxins. They are the only causative agents of two severe neuroparalytic diseases, namely tetanus and botulism. The peripheral muscle spasms which characterise tetanus are due to a blockade of inhibitory (GABAergic and glycinergic) synapses in the central nervous system leading to a motor neurones desinhibition. In contrast, botulism symptoms are only peripheral. They are consequent to a near irreversible and highly selective inhibition of acetyl-choline release at the motor nerve endings innervating skeletal muscles. During the past decade, the cellular and molecular modes of action of clostridial neurotoxins has been near completely elucidated. After a binding step of the neurotoxins to specific membrane acceptors located only on nerve terminals, BoNTs and TeNT are internalized into neurons. Inside their target neurones, the intracellularly active moiety (their light chain) is translocated from the endosomal compartment to the cytosol. The neurotoxins' light chains are zinc-dependent (endopeptidases which are specific for one among three synaptic proteins (VAMP/synaptobrevin, syntaxin or SNAP-25) implicated in neurotransmitter exocytosis. The presence of distinct targets for BoNTs and TeNT correlates well with the observed quantal alterations of neurotransmitter release which characterize certain toxin serotypes. In addition, evidence for a second, non-proteolytic, inhibitory mechanism of action has been provided recently. Most likely, this additional blocking action involves the activation of neurone transglutaminases. Due to their specific action on key proteins of the exocytosis apparatus, clostridial neurotoxins are now widely used as molecular tools to study exocytosis.

Dermal dendrocytes represent a population of resident cells of the dermis identified recently by virtue of the immunohistochemical expression of the coagulation factor XIIIa (fXIIIa). These dendritic cells of bone-marrow origin bear particular histoenzymatic and immunohistochemical features, some of which are shared with antigen-presenting cells; however, they are clearly distinct from epidermal Langerhans cells. Dermal dendrocytes could act as macrophages, antigen-presenting cells or participate in the homeostasis of macromolecules of the dermis. These cells give rise to some cutaneous tumours and seem involved in inflammatory dermatoses where they act by means of cytokine production; they could even represent targets of HIV infection. Future functional studies will hopefully lead to a better understanding of their precise role in normal and diseased skin, which remains presently partly speculative.

The existence of dermal dendrocytes as perivascular dendritic macrophages, first described six years ago, has now been widely accepted. These cells are most reliably identified immunohistochemically by the marker factor XIIIa and form a resident network in normal human cutaneous tissue. They appear to play an important role in phagocytosis, inflammation and immunocompetence. In addition, they form the constituent cell of several fibroproliferative and neoplastic skin disorders. This article offers an update of dermal dendrocytes and factor XIIIa in normal and pathological skin.

This review summarizes recent data on the keratinocyte, the major cell type in the epidermis. A two-state model is proposed: in the "resting" state, the keratinocyte is committed to a program of terminal differentiation focusing on production of an efficient barrier, the stratum corneum, and of the epidermal basement membrane; the activated state, first discovered in cell culture studies, occurs in vivo during epidermal wound healing and inflammatory skin diseases.