Immune cross-reactivity in celiac disease: anti-gliadin antibodies bind to neuronal synapsin I.
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.
Alaedini
Armin
A
Department of Neurology and Neuroscience, Cornell University, and St. Vincent's Hospital Manhattan, New York, NY 10021, USA. ara2004@med.cornell.edu
Okamoto
Haruka
H
Briani
Chiara
C
Wollenberg
Kurt
K
Shill
Holly A
HA
Bushara
Khalafalla O
KO
Sander
Howard W
HW
Green
Peter H R
PH
Hallett
Mark
M
Latov
Norman
N
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*
D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D016704:Synapsins; D005903:Gliadin