Alcohol Induces Sensitization to Gluten in Genetically Susceptible Individuals: A Case Control Study

Abstract

BackgroundThe mechanisms of cerebellar degeneration attributed to prolonged and excessive alcohol intake remain unclear. Additional or even alternative causes of cerebellar degeneration are often overlooked in suspected cases of alcohol-related ataxia. The objectives of this study were two fold: (1) to investigate the prevalence of gluten-related serological markers in patients with alcohol-related ataxia and; (2) to compare the pattern of brain involvement on magnetic resonance imaging between patients with alcohol and gluten ataxias.Materials & MethodsPatients diagnosed with alcohol and gluten ataxias were identified from a retrospective review of patients attending a tertiary clinic. HLA genotype and serological markers of gluten-related disorders were recorded. Cerebellar volumetry, MR spectroscopy and voxel-based morphometric analyses were performed on patients and compared with matched control data.ResultsOf 904 registered patients, 104 had alcohol ataxia and 159 had gluten ataxia. 61% of the alcohol ataxia group and 70% of the gluten ataxia group had HLA DQ2/DQ8 genotype compared to 30% in healthy local blood donors. 44% of patients with alcohol ataxia had antigliadin antibodies compared to 12% in the healthy local population and 10% in patients with genetically confirmed ataxias. None of the patients with alcohol ataxia and antigliadin antibodies had celiac disease compared to 40% in patients with gluten ataxia. The pattern of structural brain abnormality in patients with alcohol ataxia who had antigliadin antibodies differed from gluten ataxia and was identical to that of alcohol ataxia.ConclusionsAlcohol related cerebellar degeneration may, in genetically susceptible individuals, induce sensitization to gluten. Such sensitization may result from a primary cerebellar insult, but a more systemic effect is also possible. The duration and amount of exposure to alcohol may not be the only factors responsible for the cerebellar insult.

Causes of progressive cerebellar ataxia: prospective evaluation of 1500 patients

“…Yet the aetiology of cerebellar degeneration in the context of excessive alcohol intake remains obscure. The toxic effect of alcohol on the cerebellum is a factor but genetic and autoimmune predisposition may contribute 6 19…”

Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

“…The authors concluded that cerebellar neuronal physiology is abnormal in patients with GA even in the absence of cerebellar structural deficit and that MR spectroscopy may prove a useful tool for monitoring disease. However, more recent work has indicated that the MR spectroscopy was only statistically abnormal compared to controls from the vermis which also reflects the pattern of atrophy seen, which affects the vermis earlier and more severely than the hemispheres [48, 49]. There is no published longitudinal evidence of the use of MR spectroscopy for follow up of patients with GA.…”

Alcohol-related cerebellar degeneration: not all down to toxicity?

“…Proposed mechanisms for the high prevalence of TG2 autoantibodies in patients with chronic alcohol abuse include increased gut permeability associated with alcohol induced intestinal mucosal lesions [ 9 ] leading to increased exposure of the immune system to pathogenic antigens (including gluten peptides). In line with this, alcohol has been shown to induce sensitisation to gluten in genetically susceptible individuals [ 12 ].…”