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Gluten neuropathy: electrophysiological progression and HLA associations



Gluten neuropathy (GN) is the term used to describe peripheral neuropathy that occurs in patients with gluten sensitivity (GS) or coeliac disease (CD) in the absence of other risk factors. We aimed to describe the neurophysiological progression rate of GN across time and look into the potential role of genetic susceptibility in its development.


This is a cohort study of 45 patients with GN with a mean follow-up period of 8 ± 5 years. The assessments included clinical and neurophysiological data and HLA-DQ genotyping.


The mean age at diagnosis was 60 ± 12 years. The majority of patients had a length-dependent neuropathy (75.6%), whereas the rest were diagnosed with sensory ganglionopathy (SG).

DQA1*02-positive patients were more likely to suffer with SG compared to the DQA1*02 negative patients (60% versus 13.8%, p = 0.009). There was also a trend for statistical significance regarding the DQB1*06 allele and the DQA1*01/DQB1*06 haplotype were found more frequently in patients with GN than in healthy controls (p = 0.026 and p = 0.047, respectively). A linear effect of time on the neurophysiological findings was found in radial sensory nerve action potential (1.9% mean annual decrement, p = 0.036), sural sensory nerve action potential (3.3% mean annual decrement, p = 0.013) and tibial nerve motor compound action potential (6.5% mean annual decrement, p < 0.001) amplitudes, independently from age or gender.


GN is a late manifestation of GS and CD. The majority of patients have the length-dependent neuropathy with a linear deterioration over time. HLA genotyping of GS and CD patients who suffer from neuropathic symptoms is recommended as it can help identifying patients at risk for developing SG.

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We would like to thank Dr Dasappaiah Ganesh Rao for his contribution in the data collection. We would like to thank all participants in the study.



Author information




P.Z.: drafting/revising the manuscript, data collection, statistical analysis, accept responsibility for conduct of research and final approval. M.H., D.S. and P.G.S.: drafting/revising the manuscript, data collection, accept responsibility for conduct of research and final approval. A.A.: drafting/revising the manuscript, statistical analysis, accept responsibility for conduct of research and final approval.

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Correspondence to Panagiotis Zis.

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The authors declare no conflict of interest.

Ethical standards

The study protocol has been approved by the local ethics committee.


Panagiotis Zis, Ptolemaios Georgios Sarrigiannis, Artemios Artemiadis, David Sanders and Marios Hadjivassiliou have nothing to disclose.

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Zis, P., Sarrigiannis, P., Artemiadis, A. et al. Gluten neuropathy: electrophysiological progression and HLA associations. J Neurol 268, 199–205 (2021).

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  • Peripheral neuropathy
  • Gluten sensitivity
  • Coeliac disease
  • Progression
  • HLA genotyping