title: Gluten exacerbates IgA nephropathy in humanized mice through gliadin-CD89 interaction.
abstract: IgA1 complexes containing deglycosylated IgA1, IgG autoantibodies, and a soluble form of the IgA receptor (sCD89), are hallmarks of IgA nephropathy (IgAN). Food antigens, notably gluten, are associated with increased mucosal response and IgAN onset, but their implication in the pathology remains unknown. Here, an IgAN mouse model expressing human IgA1 and CD89 was used to examine the role of gluten in IgAN. Mice were given a gluten-free diet for three generations to produce gluten sensitivity, and then challenged for 30 days with a gluten diet. A gluten-free diet resulted in a decrease of mesangial IgA1 deposits, transferrin 1 receptor, and transglutaminase 2 expression, as well as hematuria. Mice on a gluten-free diet lacked IgA1-sCD89 complexes in serum and kidney eluates. Disease severity depended on gluten and CD89, as shown by reappearance of IgAN features in mice on a gluten diet and by direct binding of the gluten-subcomponent gliadin to sCD89. A gluten diet exacerbated intestinal IgA1 secretion, inflammation, and villous atrophy, and increased serum IgA1 anti-gliadin antibodies, which correlated with proteinuria in mice and patients. Moreover, early treatment of humanized mice with a gluten-free diet prevented mesangial IgA1 deposits and hematuria. Thus, gliadin-CD89 interaction may aggravate IgAN development through induction of IgA1-sCD89 complex formation and a mucosal immune response. Hence, early-stage treatment with a gluten-free diet could be beneficial to prevent disease.
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Center for Research on Inflammation, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] Inflamex Laboratory of Excellence, Faculté de Médecine Paris Diderot, Site Xavier Bichat, Paris, France [4] CNRS ERL8252, Paris, France.
authors: Christina
authors: C
authors: Papista
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Center for Research on Inflammation, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] Inflamex Laboratory of Excellence, Faculté de Médecine Paris Diderot, Site Xavier Bichat, Paris, France [4] CNRS ERL8252, Paris, France.
authors: Sebastian
authors: S
authors: Lechner
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Center for Research on Inflammation, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] Inflamex Laboratory of Excellence, Faculté de Médecine Paris Diderot, Site Xavier Bichat, Paris, France [4] CNRS ERL8252, Paris, France.
authors: Sanae
authors: S
authors: Ben Mkaddem
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Center for Research on Inflammation, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] Inflamex Laboratory of Excellence, Faculté de Médecine Paris Diderot, Site Xavier Bichat, Paris, France [4] CNRS ERL8252, Paris, France.
authors: Marie-Bénédicte
authors: MB
authors: LeStang
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Center for Research on Inflammation, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] Inflamex Laboratory of Excellence, Faculté de Médecine Paris Diderot, Site Xavier Bichat, Paris, France [4] CNRS ERL8252, Paris, France.
authors: Lilia
authors: L
authors: Abbad
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Center for Research on Inflammation, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] Inflamex Laboratory of Excellence, Faculté de Médecine Paris Diderot, Site Xavier Bichat, Paris, France [4] CNRS ERL8252, Paris, France.
authors: Julie
authors: J
authors: Bex-Coudrat
authors: Service de Néphrologie, Hôpital Saint-Louis, Paris, France.
authors: Evangéline
authors: E
authors: Pillebout
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Center for Research on Inflammation, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] Inflamex Laboratory of Excellence, Faculté de Médecine Paris Diderot, Site Xavier Bichat, Paris, France [4] CNRS ERL8252, Paris, France.
authors: Jonathan M
authors: JM
authors: Chemouny
authors: Néphrologie, Paris, France.
authors: Mathieu
authors: M
authors: Jablonski
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Center for Research on Inflammation, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] CNRS ERL8252, Paris, France [4] Exploration fonctionnelle, Paris, France.
authors: Martin
authors: M
authors: Flamant
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Center for Research on Inflammation, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] Inflamex Laboratory of Excellence, Faculté de Médecine Paris Diderot, Site Xavier Bichat, Paris, France [4] CNRS ERL8252, Paris, France [5] Néphrologie, Paris, France.
authors: Eric
authors: E
authors: Daugas
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Center for Research on Inflammation, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] Inflamex Laboratory of Excellence, Faculté de Médecine Paris Diderot, Site Xavier Bichat, Paris, France [4] CNRS ERL8252, Paris, France [5] Néphrologie, Paris, France.
authors: François
authors: F
authors: Vrtovsnik
authors: Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors: Minas
authors: M
authors: Yiangou
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Center for Research on Inflammation, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] Inflamex Laboratory of Excellence, Faculté de Médecine Paris Diderot, Site Xavier Bichat, Paris, France [4] CNRS ERL8252, Paris, France.
authors: Laureline
authors: L
authors: Berthelot
authors: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1149, Center for Research on Inflammation, Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] Inflamex Laboratory of Excellence, Faculté de Médecine Paris Diderot, Site Xavier Bichat, Paris, France [4] CNRS ERL8252, Paris, France [5] Immunologie, Assistance Publique de Paris, DHU Fire, Hôpital Bichat-Claude Bernard, Paris, France.
authors: Renato C
authors: RC
authors: Monteiro
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000097:blood / Q000378:metabolism*; D001284:Atrophy / Q000209:etiology; D055050:Diet, Gluten-Free; D004195:Disease Models, Animal; D004751:Enteritis / Q000209:etiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D005903:Gliadin / Q000276:immunology / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000178:diet therapy / Q000276:immunology* / Q000378:metabolism*; D005983:Glutens / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D006417:Hematuria / Q000178:diet therapy / Q000209:etiology; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011507:Proteinuria / Q000209:etiology; D011961:Receptors, Fc / Q000097:blood / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc; D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse; D005983:Glutens; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins