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.

Epitope-Specific Evolution of Human B Cell Responses to Borrelia burgdorferi VlsE Protein from Early to Late Stages of Lyme Disease

“…Collection of serum for immunoblotting and immunoflouorescence analyses was done on day 0 (preimmunization) and day 55 (postimmunization). Abs from pooled sera for each peptide immunization were purified by affinity chromatography, using peptidecoupled affinity columns, as described previously (32). Reactivity of the generated rabbit sera and affinity-purified Abs to each peptide was confirmed at serial dilutions by ELISA, using the same procedure as described above, except HRP-conjugated donkey anti-rabbit IgG (GE Healthcare Life Sciences) was used as the secondary Ab.…”

Cross-Reaction between Gliadin and Different Food and Tissue Antigens

“…During the past decade, it has been well established that CD is associated with various extraintestinal autoimmunities that involve the thyroid, joints, heart, skin, pancreas, bone, liver, reproductive organs, and the nervous system [38][39][40][41][42][43][44][45][46][47]. Although the exact mechanisms for the induction of these autoimmunities are not definitively known, there is a growing body of evidence indicating that these diseases may result from molecular mimicry between gliadin or transglutaminase and various tissue antigens, including nervous system proteins [8,[41][42][43]48].…”

“…Although the exact mechanisms for the induction of these autoimmunities are not definitively known, there is a growing body of evidence indicating that these diseases may result from molecular mimicry between gliadin or transglutaminase and various tissue antigens, including nervous system proteins [8,[41][42][43]48]. Interestingly, the celiac peptide VVKVGGSSSLGW shares more than 30% homology with the transglutaminase peptide 476-487 (RIRVGQSMNMGS) [8].…”

Molecular mimicry in neurological disease: what is the evidence?

“…These include autoimmunity to the B peptide (amino acids 372 -395) of the glutamate/AMPA (a-3-hydroxy-5-methyl-4-isoxazolepropionic acid) subtype 3 receptor which may be associated with cross-reactivity to dsDNA or influenza A vaccination in patients with Rasmussens encephalitis. In addition, there are preliminary data showing cross-reactivity between gliadin and neuronal synapsin I in patients with celiac disease (which can be complicated by neurological syndromes such as neuropathy, seizures and behavioral changes) [157,162]. Finally, molecular mimicry may contribute to the pathogenesis of patients with APS that develop chorea [6,163].…”