title: [Formation of IgA deposits in Berger's disease: what we learned from animal models].
abstract: Immunoglobulin A (IgA) nephropathy (N) is the most common form of primary glomerulonephritis in the world and one of the first cause of end-stage renal failure. IgAN is characterized by the accumulation in mesangial areas of immune complexes containing IgA1. While epidemiology and clinical studies of IgAN are well-established, the mechanism(s) underlying disease development is poorly understood. The pathogenesis of this disease involves the deposition of polymeric and undergalactosylated IgA1 in the mesangium. Quantitative and structural changes of IgA1 play a key role in the development of the disease, due to functional abnormalities of two IgA receptors: the FcαR (CD89) expressed by blood myeloid cells and the transferrin receptor (TfR1) on mesangial cells. Abnormal IgA induces release of soluble CD89, responsible for the formation of circulating IgA complexes. These complexes are trapped by the TfR1 that is overexpressed on mesangial cells in IgAN patients, inducing the expression of transglutaminase 2. This enzyme stabilises IgA deposits at the surface of mesangial cells. These cells are then activated, proliferate and produce proinflammatory cytokines, leading to the loss of renal function.
authors.affiliation: INSERM U699, Faculté Bichat, 16 rue Henri Huchard, 75018 Paris, France - Université Paris Diderot, Faculté de Médecine, Site Bichat, 16 rue Henri Huchard, 75890 Paris Cedex 18, France - Laboratoire d'Excellence Inflamex, Sorbonne Paris Cité, 75890 Paris Cedex 18, France.
authors.forename: Laureline
authors.initials: L
authors.lastname: Berthelot
authors.affiliation: INSERM U699, Faculté Bichat, 16 rue Henri Huchard, 75018 Paris, France - Université Paris Diderot, Faculté de Médecine, Site Bichat, 16 rue Henri Huchard, 75890 Paris Cedex 18, France - Laboratoire d'Excellence Inflamex, Sorbonne Paris Cité, 75890 Paris Cedex 18, France.
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005922:Glomerulonephritis, IGA / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000378:metabolism*; D011961:Receptors, Fc / Q000502:physiology
chemical_list: C045281:IgA receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc