Increased prevalence of transglutaminase 6 antibodies in sera from schizophrenia patients

Schizophr Bull. 2013 Jul;39(4):867-71. doi: 10.1093/schbul/sbs064. Epub 2012 Apr 19.


Gluten can cause extraintestinal manifestations with or without gastrointestinal symptoms and elevated antitissue transglutaminase 2 (tTG2) autoantibodies. Organ-specific gluten reaction involves immune response toward other transglutaminase (TG) isoforms including tTG3 (expressed in the skin, leading to dermatitis herpetiformis) and tTG6 (expressed in the brain, causing gluten ataxia). This analysis focuses on tTG6 antibodies, which have never been studied before in schizophrenia (SZ) and its relationships to tTG2 and to antigliadin antibodies. We previously showed an increased prevalence of tTG2 antibodies in gluten sensitive SZ patients compared with healthy controls (HC) that was not paralleled by an increased prevalence of antiendomysial antibody. To elucidate this discrepancy, we examined those tTG2 positive SZ patients for the presence of tTG6 antibody. We also searched for tTG6 antibodies in our sample of antigliadin (AGA) positive and AGA and tTG2 negative SZ patients. Seventy-four tTG2 positive SZ patients were compared with 148 age and gender-matched HC. Of the 74 tTG2 positive SZ patients, 16 were positive for tTG6 IgA for a prevalence of 22%. Only 4 HC were positive for tTG6 IgA for a prevalence of 2.7%. Among the AGA positive SZ patients, the prevalence of tTG6 IgA was 21.3% while 13.1% of the AGA and tTG2 negative SZ patients were positive for tTG6 IgA. The HC had a prevalence of 6%. Our results indicate a higher prevalence of tTG6 antibodies in SZ that may represent a biomarker useful to identify SZ patients who would benefit from a gluten-free diet.

Keywords: celiac disease; gluten sensitivity; gluten-free diet; schizophrenia; transglutaminase 6.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / immunology*
  • Case-Control Studies
  • Diet, Gluten-Free
  • Female
  • Gliadin / immunology
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • Schizophrenia / diet therapy
  • Schizophrenia / immunology*
  • Transglutaminases / immunology*


  • Autoantibodies
  • Immunoglobulin A
  • Immunoglobulin G
  • Gliadin
  • Transglutaminases
  • transglutaminase 6, human