title: Role of IgA receptors in the pathogenesis of IgA nephropathy.
abstract: Immunoglobulin A nephropathy (IgAN) or Berger's disease is the most common form of primary glomerulonephritis in the world and one of the first causes of end-stage renal failure. IgAN is characterized by the accumulation of immune complexes containing polymeric IgA1 in mesangial areas. The pathogenesis of this disease involves the deposition of polymeric and hypogalactosylated IgA1 (Gd-IgA1) in the mesangium. Quantitative and structural changes of Gd-IgA1 play a key role in the development of the disease due to functional abnormalities of two IgA receptors: the FcαRI (CD89) expressed by blood myeloid cells and the transferrin receptor (CD71) on mesangial cells. Abnormal Gd-IgA1 induces release of soluble CD89, which participates in the formation of circulating IgA1 complexes. These complexes are trapped by CD71 that is overexpressed on mesangial cells in IgAN patients together with the crosslinking enzyme transglutaminase 2 allowing pathogenic IgA complex formation in situ and mesangial cell activation. A humanized mouse model expressing IgA1 and CD89 develops IgAN in a similar manner as patients. In this model, a food antigen, the gliadin, was shown to be crucial for circulating IgA1 complex formation and deposition, which could be prevented by a gluten-free diet. Identification of these new partners opens new therapeutic prospects for IgAN treatment.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149 Centre de Recherche sur l'Inflammation, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Inflamex Laboratory of Excellence Site Xavier Bichat, Paris, France.|CNRS ERL8252, Paris, France.
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Lechner
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149 Centre de Recherche sur l'Inflammation, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Inflamex Laboratory of Excellence Site Xavier Bichat, Paris, France.|CNRS ERL8252, Paris, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Papista
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149 Centre de Recherche sur l'Inflammation, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Inflamex Laboratory of Excellence Site Xavier Bichat, Paris, France.|CNRS ERL8252, Paris, France.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Chemouny
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149 Centre de Recherche sur l'Inflammation, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.|Inflamex Laboratory of Excellence Site Xavier Bichat, Paris, France.|CNRS ERL8252, Paris, France.
authors.forename: Laureline
authors.initials: L
authors.lastname: Berthelot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149 Centre de Recherche sur l'Inflammation, Paris, France. renato.monteiro@inserm.fr.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France. renato.monteiro@inserm.fr.|Inflamex Laboratory of Excellence Site Xavier Bichat, Paris, France. renato.monteiro@inserm.fr.|CNRS ERL8252, Paris, France. renato.monteiro@inserm.fr.|Service d'Immunologie, Assistance Publique de Paris, DHU Fire, Hôpital Bichat, Paris, France. renato.monteiro@inserm.fr.
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D002446:Celiac Disease / Q000178:diet therapy / Q000276:immunology / Q000378:metabolism; D055050:Diet, Gluten-Free; D004195:Disease Models, Animal; D005903:Gliadin / Q000276:immunology; D005922:Glomerulonephritis, IGA / Q000175:diagnosis / Q000178:diet therapy / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D011961:Receptors, Fc / Q000276:immunology* / Q000378:metabolism; D011990:Receptors, Transferrin / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; C036832:Fc(alpha) receptor; C045281:IgA receptor; D007070:Immunoglobulin A; D008024:Ligands; D011961:Receptors, Fc; D011990:Receptors, Transferrin; D005903:Gliadin
keywords: CD89; Gluten; IgA glycosylation; IgA nephropathy; IgA receptors; Primary glomerulonephritis