<p>Coeliac disease (CD) is a multifactorial disease of the small intestine. In genetically predisposed individuals the, ingestion of cereals leads to a remodulation of the mucosal architecture, and the production of autoantibodies against tissue transglutaminase (tTG). The treatment is a lifelong gluten-free diet.</p><p>The diagnostic procedure relies on the examination of a small-bowel biopsy that displays villous atrophy. A spectrum of clinical manifestations is associated with CD, ranging from overt enteropathy to atypical and silent symptoms. Approximately 1% of the general population has CD, and the majority is undiagnosed. Although most patients with active CD can be detected by the assessment of elevated IgA-tTG, some patients lack these antibodies. Moreover, individuals with IgA-deficiency cannot be identified by means of IgA serology. </p><p>The aim of this thesis was to investigate the clinical utility of IgG-tTG for the detection and follow-up of subjects with active CD. The included studies showed that IgG-tTG was highly prevalent in IgA-deficient and IgA-competent patients with CD, whereas non-CD patients rarely had these antibodies. During a gluten-free diet, IgG-tTG decreased, demonstrating that IgG-tTG can be used to follow the patient’s adherence such a diet. Furthermore, 10% of healthy IgA deficient blood donors had elevated IgG-tTG, indicating that they had silent CD. </p><p>In IgA-competent subjects, high IgG-tTG levels correlated with a severe mode of CD and profound mucosal deterioration, suggesting that IgG-tTG might be involved in the disease progression. Moreover, we found that although a considerable percentage of IgA-competent patients lack IgG-tTG, the presence of these antibodies in conjunction with high levels of IgA-tTG was highly predictive of a severe small-intestine villous atrophy. It was also demonstrated that IgG-tTG normalisation coincided with clinical remission in IgA-competent CD patients on a gluten-free diet. </p>

Coeliac disease (CD) is a multifactorial disease of the small intestine. In genetically predisposed individuals the, ingestion of cereals leads to a remodulation of the mucosal architecture, and the production of autoantibodies against tissue transglutaminase (tTG). The treatment is a lifelong gluten-free diet. The diagnostic procedure relies on the examination of a small-bowel biopsy that displays villous atrophy. A spectrum of clinical manifestations is associated with CD, ranging from overt enteropathy to atypical and silent symptoms. Approximately 1% of the general population has CD, and the majority is undiagnosed. Although most patients with active CD can be detected by the assessment of elevated IgA-tTG, some patients lack these antibodies. Moreover, individuals with IgA-deficiency cannot be identified by means of IgA serology. The aim of this thesis was to investigate the clinical utility of IgG-tTG for the detection and follow-up of subjects with active CD. The included studies showed that IgG-tTG was highly prevalent in IgA-deficient and IgA-competent patients with CD, whereas non-CD patients rarely had these antibodies. During a gluten-free diet, IgG-tTG decreased, demonstrating that IgG-tTG can be used to follow the patient’s adherence such a diet. Furthermore, 10% of healthy IgA deficient blood donors had elevated IgG-tTG, indicating that they had silent CD. In IgA-competent subjects, high IgG-tTG levels correlated with a severe mode of CD and profound mucosal deterioration, suggesting that IgG-tTG might be involved in the disease progression. Moreover, we found that although a considerable percentage of IgA-competent patients lack IgG-tTG, the presence of these antibodies in conjunction with high levels of IgA-tTG was highly predictive of a severe small-intestine villous atrophy. It was also demonstrated that IgG-tTG normalisation coincided with clinical remission in IgA-competent CD patients on a gluten-free diet.

La perception de la viande bovine par le consommateur est un enjeu crucial pour l’industrie de la viande. La tendreté reste l’une des qualités organoleptiques essentielle aux yeux du consommateur, avec la jutosité et la flaveur. L’objectif de ma thèse a été d’étudier les propriétés structurales et biochimiques du tissu conjonctif intramusculaire responsables de la dureté de base et de faire le lien avec la tendreté et plus largement avec les qualités organoleptiques de la viande. Le développement et la mise au point d’une méthode d’analyse d’images a permis d’étudier objectivement les caractéristiques des composantes périmysiale et endomysiale du tissu conjonctif intramusculaire et de montrer que la surface occupée par ces deux structures influençait la tendreté de la viande. Préalablement à l’étude biochimique et moléculaire du tissu conjonctif intramusculaire le dosage des protéoglycanes totaux a été développé et mis en place au laboratoire. Les résultats de cette deuxième partie ont permis de mettre en avant la complémentarité entre protéoglycanes, collagène total et liaisons de réticulation au sein du muscle et leur rôle sur la jutosité. Par ailleurs, nous avons pu mettre en évidence le rôle positif des protéoglycanes de haut poids moléculaire sur la jutosité, alors que les protéoglycanes de faible poids moléculaire, telle que la décorine,joueraient plutôt un rôle sur la dureté de la viande. L’ensemble des résultats obtenus confirme nos hypothèses, à savoir que la composante structurale ainsi que les molécules minoritairement présentes dans le tissu conjonctif peuvent influencer les qualités organoleptiques de la viande bovine. / The perception of beef by consumers is a crucial issue for the meat industry. Tenderness remains one of the sensory qualities essential to the consumer, with the juiciness and flavour. The aim of my thesis was to study the structural and biochemical properties of intramuscular connective tissue responsible for the background toughness and study relationships with tenderness and more widely with the sensory qualities of beef. The development of a method of image analysis was used to study objectively the characteristics of the perimysial and endomysial component of the intramuscular connective tissue. The results showed that the area occupied by these two structures influenced the beef tenderness. An assay for total proteoglycan measurement has been developed previously to the study of biochemical and molecular characteristics intramuscular connective tissue. The results obtained in this second part have highlighted the complementarities between proteoglycans, total collagen and cross-links within the muscle and their role on the juiciness. Furthermore, we were able to highlight the positive role of high molecular weight proteoglycans on juiciness, while low molecular weight proteoglycans, such as decorin, rather played a role in beef toughness. The overall results confirm our hypothesis that the structural components of the connective tissue and the small quantity of extracellular matrix molecules could influence the sensory qualities of beef.