What is the relationship between anti-gliadin antibodies and ataxia (cerebellar degeneration)?

From the Guidelines

There is no established relationship between anti-gliadin antibodies and ataxia (cerebellar degeneration) that warrants a gluten-free diet as a preventative measure, as evidenced by the lack of positive effects in patients with multiple sclerosis 1. The current understanding of the connection between gluten and neuro-immunological diseases, such as multiple sclerosis, suggests that the hypothesis of gluten hypersensitivity contributing to these conditions is not supported by further studies 1. Key points to consider include:

• The absence of anti-gliadin antibodies and morphological changes in the gut mucosa in patients with multiple sclerosis 1
• The lack of significant positive effect of withdrawing gluten-containing foods from the diet of patients with multiple sclerosis 1
• The strong consensus (100% agreement) among experts that a gluten-free diet is not recommended to prevent multiple sclerosis, as stated in the ESPEN guideline on clinical nutrition in neurology 1 In clinical practice, the focus should be on managing symptoms and monitoring disease progression rather than implementing a gluten-free diet as a preventative measure for ataxia or cerebellar degeneration. Considerations for patient care include:
• Regular follow-up with a neurologist to monitor disease progression
• Management of symptoms as they arise
• Avoiding unnecessary dietary restrictions without evidence-based justification 1

From the Research

Relationship Between Anti-Gliadin Antibodies and Ataxia

• The presence of anti-gliadin antibodies has been linked to ataxia, particularly in patients with gluten sensitivity or celiac disease 2, 3, 4.
• Studies have shown that patients with gluten ataxia, a condition characterized by idiopathic ataxia and positive anti-gliadin antibodies, often respond to a gluten-free diet 3, 4, 5.
• The exact mechanism by which anti-gliadin antibodies contribute to ataxia is unclear, but it is thought to involve an immune response to gluten that affects the cerebellum 6.

Prevalence of Anti-Gliadin Antibodies in Ataxia Patients

• One study found that 15% of all ataxia patients and 40% of idiopathic sporadic ataxia patients had positive anti-gliadin antibodies 4.
• Another study found that 12 out of 33 patients with subacute or chronic ataxia had positive anti-gliadin antibodies, and 8 of these patients were diagnosed with gluten ataxia 6.

Effect of Gluten-Free Diet on Ataxia Patients with Anti-Gliadin Antibodies

• Studies have shown that a gluten-free diet can improve or stabilize ataxia symptoms in patients with gluten ataxia and positive anti-gliadin antibodies 3, 4, 5.
• One study found that 98% of patients with gluten ataxia who adhered to a strict gluten-free diet showed improvement in cerebellar magnetic resonance spectroscopy (MRS) results, compared to only 26% of patients who did not adhere to the diet 5.

Pathophysiological Mechanisms

• Two possible pathophysiological mechanisms have been proposed to explain the relationship between anti-gliadin antibodies and ataxia: overexpression of cerebellar epitopes and molecular mimicry with cross-reactivity of antigens directed against gliadin and Purkinje cells epitopes 6.
• Further research is needed to fully understand the relationship between anti-gliadin antibodies and ataxia, and to determine the exact mechanisms by which gluten sensitivity contributes to neurological dysfunction 2, 3, 4, 5, 6.