title: Immune cross-reactivity in celiac disease: anti-gliadin antibodies bind to neuronal synapsin I.
abstract: Celiac disease is an immune-mediated disorder triggered by ingestion of wheat gliadin and related proteins in genetically susceptible individuals. In addition to the characteristic enteropathy, celiac disease is associated with various extraintestinal manifestations, including neurologic complications such as neuropathy, ataxia, seizures, and neurobehavioral changes. The cause of the neurologic manifestations is unknown, but autoimmunity resulting from molecular mimicry between gliadin and nervous system proteins has been proposed to play a role. In this study, we sought to investigate the immune reactivity of the anti-gliadin Ab response toward neural proteins. We characterized the binding of affinity-purified anti-gliadin Abs from immunized animals to brain proteins by one- and two-dimensional gel electrophoresis, immunoblotting, and peptide mass mapping. The major immunoreactive protein was identified as synapsin I. Anti-gliadin Abs from patients with celiac disease also bound to the protein. Such cross-reactivity may provide clues into the pathogenic mechanism of the neurologic deficits that are associated with gluten sensitivity.
authors.affiliation: Department of Neurology and Neuroscience, Cornell University, and St. Vincent's Hospital Manhattan, New York, NY 10021, USA. ara2004@med.cornell.edu
authors.forename: Armin
authors.initials: A
authors.lastname: Alaedini
authors.forename: Haruka
authors.initials: H
authors.lastname: Okamoto
authors.forename: Chiara
authors.initials: C
authors.lastname: Briani
authors.forename: Kurt
authors.initials: K
authors.lastname: Wollenberg
authors.forename: Holly A
authors.initials: HA
authors.lastname: Shill
authors.forename: Khalafalla O
authors.initials: KO
authors.lastname: Bushara
authors.forename: Howard W
authors.initials: HW
authors.lastname: Sander
authors.forename: Peter H R
authors.initials: PH
authors.lastname: Green
authors.forename: Mark
authors.initials: M
authors.lastname: Hallett
authors.forename: Norman
authors.initials: N
authors.lastname: Latov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D001666:Binding Sites, Antibody; D001921:Brain / Q000276:immunology / Q000378:metabolism; D002446:Celiac Disease / Q000276:immunology*; D003429:Cross Reactions; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000276:immunology* / Q000378:metabolism*; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D016704:Synapsins / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D016704:Synapsins; D005903:Gliadin