Transglutaminase 6 antibodies in gluten neuropathy

Dig Liver Dis. 2017 Nov;49(11):1196-1200. doi: 10.1016/j.dld.2017.08.019. Epub 2017 Aug 10.


Background: TG6 antibodies have been shown to be a marker of gluten ataxia but their presence in the context of other neurological manifestations of gluten sensitivity has not been explored. We investigated the presence of TG6 antibodies in gluten neuropathy (GN), defined as as an otherwise idiopathic peripheral neuropathy associated with serological markers of gluten sensitivity (one or more of antigliadin IgG and/or IgA, endomysial and transglutaminase-2 antibodies).

Methods: This was a cross-sectional study conducted at the Sheffield Institute of Gluten Related Diseases, Royal Hallamshire Hospital, Sheffield, UK. Blood samples were collected whilst the patients were on a gluten containing diet. Duodenal biopsies were performed to establish the presence of enteropathy.

Results: Twenty-eight patients were recruited (mean age 62.5±13.7 years). Fifteen (53.6%) had sensory ganglionopathy, 12 (42.9%) had symmetrical axonal neuropathy and 1 had mononeuritis multiplex. The prevalence of TG6 antibodies was 14 of 28 (50%) compared to 4% in the healthy population. TG6 antibodies were found in 5/15 (33.3%) patients with sensory ganglionopathy and in 8/12 (66.7%) with symmetrical axonal neuropathy. Twenty-four patients underwent duodenal biopsy 11 (45.8%) of which had enteropathy. The prevalence of TG6 was not significantly different when comparing those with or without enteropathy.

Conclusions: We found a high prevalence of antibodies against TG6 in patients with GN. This suggests that TG6 involvement is not confined to the central nervous system. The role of transglutaminase 6 in peripheral nerve function remains to be determined but TG6 antibodies may be helpful in the diagnosis of GN.

Keywords: Gluten; Peripheral neuropathy; TG6 antibodies.

MeSH terms

  • Aged
  • Axons
  • Biomarkers / blood
  • Biopsy
  • Cross-Sectional Studies
  • Duodenum / pathology
  • Female
  • GTP-Binding Proteins / immunology
  • Ganglia, Sensory
  • Gliadin / immunology
  • Glutens / adverse effects*
  • Humans
  • Immunoglobulin A / blood*
  • Immunoglobulin G / blood*
  • Male
  • Middle Aged
  • Mononeuropathies / blood
  • Peripheral Nervous System Diseases / blood*
  • Peripheral Nervous System Diseases / immunology
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases / immunology*


  • Biomarkers
  • Immunoglobulin A
  • Immunoglobulin G
  • Glutens
  • Gliadin
  • Protein Glutamine gamma Glutamyltransferase 2
  • TGM6 protein, human
  • Transglutaminases
  • GTP-Binding Proteins