title: Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease.
abstract: Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We show that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation. In patients with active CD, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact p31-49 and 33-mer peptides was blocked by polymeric and secretory IgA (SIgA) and by soluble CD71 receptors, pointing to a role of SIgA-gliadin complexes in this abnormal intestinal transport. This retrotranscytosis of SIgA-gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa, thereby triggering an immune response and perpetuating intestinal inflammation. Our findings strongly implicate CD71 in the pathogenesis of CD.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U793, Paris 75730, Cedex 15, France.
authors.forename: Tamara
authors.initials: T
authors.lastname: Matysiak-Budnik
authors.forename: Ivan Cruz
authors.initials: IC
authors.lastname: Moura
authors.forename: Michelle
authors.initials: M
authors.lastname: Arcos-Fajardo
authors.forename: Corinne
authors.initials: C
authors.lastname: Lebreton
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ménard
authors.forename: Céline
authors.initials: C
authors.lastname: Candalh
authors.forename: Karima
authors.initials: K
authors.lastname: Ben-Khalifa
authors.forename: Christophe
authors.initials: C
authors.lastname: Dugave
authors.forename: Houda
authors.initials: H
authors.lastname: Tamouza
authors.forename: Guillaume
authors.initials: G
authors.lastname: van Niel
authors.forename: Yoram
authors.initials: Y
authors.lastname: Bouhnik
authors.forename: Dominique
authors.initials: D
authors.lastname: Lamarque
authors.forename: Stanislas
authors.initials: S
authors.lastname: Chaussade
authors.forename: Georgia
authors.initials: G
authors.lastname: Malamut
authors.forename: Christophe
authors.initials: C
authors.lastname: Cellier
authors.forename: Nadine
authors.initials: N
authors.lastname: Cerf-Bensussan
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
authors.forename: Martine
authors.initials: M
authors.lastname: Heyman
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D001706:Biopsy; D002446:Celiac Disease / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D020895:Enterocytes / Q000378:metabolism; D005903:Gliadin / Q000737:chemistry*; D005922:Glomerulonephritis, IGA / Q000175:diagnosis / Q000473:pathology; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008954:Models, Biological; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry*; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000737:chemistry*
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D007070:Immunoglobulin A; D010455:Peptides; D011990:Receptors, Transferrin; D005903:Gliadin