Rôle de l’environnement microbien dans la régulation de l’immunoglobuline A mucosale et dans le développement de la maladie de Berger

Abstract : IgA nephropathy is the most frequent glomerulonephritis worldwide. It features mesangial immunoglobulin (Ig)A deposits and proteinuria, hematuria and glomerular histological lesions. In 25% patients, it evolves, within 20 years, towards the end stage renal disease. Microbial environment, through the interaction with mucosa, is believed to play a crucial role in the development of the disease. The objectives of my work were to evaluate the effect of the microbial compound lipopolysaccharide (LPS) on the production of the nephritogenic IgA in the mucosa of mice and on the development of IgA nephropathy in the murine model 1KI that spontaneously develops mesangial IgA deposits without the other signs of the disease. Our results and those previously published suggest that the chronic stimulation of mucosa by microbiota leads to the increased production of nephritogenic IgA in the mucosa. These IgA, thanks to a deficient mucosal receptor pIgR in patients with IgA nephropathy, may be abnormally routed in the blood. We also showed that LPS provokes hematuria in the 1KI mice, when they express a specific IgA receptor, CD89, on the surface of polymorphonuclear neutrophils. Altogether our findings highlight the impact of microbial environment on pIgR and on polymorphonuclear neutrophils and thus, potentially, on IgA nephropathy.
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Anderson Archelus. Rôle de l’environnement microbien dans la régulation de l’immunoglobuline A mucosale et dans le développement de la maladie de Berger. Médecine humaine et pathologie. Université de Limoges, 2018. Français. ⟨NNT : 2018LIMO0007⟩. ⟨tel-01841431⟩

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