Antigliadin antibodies harmful for brain at low levels

Antigliadin antibodies (AGA), a subset of anti-gluten antibodies, have been shown to be harmful to the brain at levels below the standard reference range in an important study on gluten ataxia (GA) published in the journal Nutrients. Gluten ataxia is a condition characterized by loss of balance due to cerebellar damage due to neuroinflammation provoked by gluten. Non-celiac gluten sensitivity (NCGS) can cause inflammation in the brian and central nervous with antibodies at lower levels than in celiac disease and in the absence of abdominal symptoms; clinicians should be attentive to the implications of lower antigliadin antibody titers.

Cerebellar damage without gastrointestinal disease

The authors note the absence of enteropathy (intestinal disease) is often the case with gluten ataxia.

"Indeed, up to 50% of patients with GA do not have an enteropathy, yet they still benefit from a gluten-free diet (GFD) [2]. For this reason, IgG and IgA native antigliadin antibodies (AGA) are currently the most sensitive marker for GA when compared to endomysium (EMA) and transglutaminase 2 antibodies (TG2), both of which are specific for the presence of enteropathy (Coeliac Disease-CD) [2]."

Moreover...

"It is now widely accepted that sensitivity to gluten can be present without enteropathy [3]. The only current serological biomarker helpful in diagnosing gluten sensitivity without enteropathy is AGA [4]."

Lower antigliadin antibody levels with gluten ataxia

Damage can occur to the brain, in this case the cerebellum, with lower levels of circulating antigliadin antibodies than typically seen in celiac disease.

"Patients with CD often have high titres of circulating AGA, whereas patients with GA and no enteropathy tend to have low titres. The serological cut-off for significant titre in commercially available AGA assays is calculated to maximize diagnostic specificity using data from patients with CD. This would not necessarily be applicable to those patients with gluten sensitivity who do not have enteropathy and those patients with extraintestinal manifestations."

In accordance with their experience of treating GA with a gluten-free diet (GFD) validated by MR (magnetic resonance), the authors determined to investigate the effect of a GFD with differing levels of antigliadin antibodies.

"Having previously demonstrated the beneficial effect of a GFD in patients with GA using MR spectroscopy of the cerebellum, in this report we present our experience of the effect of a GFD in patients with ataxia and AGA levels that are below what is considered positive, as defined by the manufacturer, but above a newly defined cut-off AGA level based on our extensive experience in managing patients with GA and the re-evaluation of over 500 patients with GA."

Improvement shown only with strict adherence to a gluten-free diet

The authors' data provides evidence verified with MR spectroscopy that a strict GFD results in objective improvements in gluten ataxia, and that lower levels of antigliadin antibodies—typically below the customary reference range—are diagnostic.

"The current study demonstrates that in patients with GA with low titres of AGA, NAA/Cr area ratio within the cerebellar vermis improves with strict adherence to a gluten-free diet, worsens with on-going exposure to gluten, and also largely worsens with partial adherence to a gluten-free diet, as indicated by persistently positive circulating AGA. The improvement in MR spectroscopy was accompanied by clinical improvement or stabilisation of the ataxia in the strict GFD group."

The authors conclude:

"Both this report and previous publications from our group have highlighted the importance of using the correct serological markers for the diagnosis of GA. The presence of enteropathy (associated with the presence of positive TG2 and endomysium antibodies) does not influence the response to the GFD, and thus any patient with positive antigliadin antibodies and no other cause of ataxia should be offered a strict gluten-free diet, even in the absence of enteropathy...In conclusion, using MR spectroscopy data we have demonstrated that patients with ataxia and low titre of AGA improve on a strict GFD. We are therefore proposing a new AGA titre cut-off level that should be used in the diagnosis of GA."

Clinical summary: health practitioners should be attentive to antigliadin antibodies at levels lower than the typical reference range, and explain to patients the importance of strict adherence to a gluten-free diet. Importantly, there are more antibodies than AGA that can reveal reactivity to gluten. In order to minimize false negatives and missed diagnoses, I recommend the use of Cyrex Array 3X - Wheat/Gluten Proteome Reactivity & Autoimmunity for the most complete and dependable assessment of anti-gluten antibodies with the concomitant measurement of total IgG and IgA to ensure adequate levels for accuracy.Readers may also be interested in Neuropsychiatric illness in non-celiac gluten sensitivity.