Gluten Ataxia Associated with Dietary Protein Cross-Reactivity with GAD-65

Datis Kharrazian

doi:10.3390/reports3030024

Abstract

Cross-reactivity occurs when antibodies formed against an antigen have amino acid sequence homology with another target protein. This allows antibodies formed against the antigen to also bind to similar proteins that share structural similarity. Autoimmune reactions to gluten can lead to sporadic ataxia in susceptible genotypes due to cross-reactivity. With gluten ataxia, dietary consumption of gluten proteins induce immunological cross-reactivity with glutamic-acid decarboxylase-65 (GAD-65) target proteins found in the cerebellum. Implementation of a strict gluten-free diet has been shown to improve the expression of this form of ataxia with most patients in this subgroup. However, there are some subjects that have limited clinical responses to only a strict gluten-free diet. Dietary protein cross-reactivity to other food proteins, besides gluten, that also share structural similarity to GAD-65 may also play a role in this reaction. In this case report, we report of a patient suffering from gluten-ataxia in which a gluten-free diet alone did not generate significant clinical outcomes until other foods that cross-react with GAD-65 were also removed from their diet.

Highlights

Gluten ataxia results from immunological damage to the cerebellum from gluten antibodies that cross-react with cerebellum tissue in genetically susceptible subgroups
Gluten ataxia should be considered in all patients with sporadic ataxia, regardless of whether they have abdominal symptoms; early diagnosis and treatment may result in neurological improvement [2]
The clinical presentation of latent autoimmune diabetes of adulthood in combination with idiopathic sporadic ataxia suggests the possibility of glutamic-acid decarboxylase-65 (GAD-65) autoimmune reactivity, since this target protein is co-expressed in both pancreatic and cerebellum tissue

Summary

Introduction

Gluten ataxia results from immunological damage to the cerebellum from gluten antibodies that cross-react with cerebellum tissue in genetically susceptible subgroups. Individuals suffering from gluten ataxia have been found to clinically improve when implementing a gluten-free diet due to cross-reactivity of dietary proteins with ataxia target sites, such as GAD-65 within the cerebellum in clinical settings [1]. Gluten ataxia should be considered in all patients with sporadic ataxia, regardless of whether they have abdominal symptoms; early diagnosis and treatment may result in neurological improvement [2]. There are subgroups of patients suffering from gluten ataxia that only have a partial resolution of their symptoms while implementing a gluten-free diet. It is not clear why these patients do not respond.

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Discussion

Conclusion