Anti-transglutaminase 6 Antibody Development in Children With Celiac Disease Correlates With Duration of Gluten Exposure

J Pediatr Gastroenterol Nutr. 2018 Jan;66(1):64-68. doi: 10.1097/MPG.0000000000001642.

Abstract

Objectives: Antibodies against transglutaminase 6 (anti-TG6) have been implicated in neurological manifestations in adult patients with genetic gluten intolerance, and it is unclear whether autoimmunity to TG6 develops following prolonged gluten exposure. We measured the anti-TG6 in children with celiac disease (CD) at the diagnosis time to establish a correlation between these autoantibodies and the duration of gluten exposure. We investigated a correlation between anti-TG6 and the presence of neurological disorders.

Methods: Anti-TG6 (IgA/IgG) were measured by ELISA in sera of children with biopsy-proven CD and of children experiencing gastrointestinal disorders. CD patients positive for anti-TG6 were retested after 2 years of gluten-free diet (GFD).

Results: We analyzed the sera of 274 CD children and of 121 controls. Anti-TG6 were detected in 68/274 (25%) CD patients and in 19/121 (16%) controls, with significant difference between the 2 groups (P = 0.04). None of the CD patients and of the controls testing positive for anti-TG6 were experiencing neurological disorders. Eleven of 18 (61%) CD patients with other autoimmune diseases were positive for anti-TG6. In CD patients, a significant correlation between the gluten exposure before the CD diagnosis and anti-TG6 concentration was found (P = 0.006 for IgA; P < 0.0001 for IgG). After GFD anti-TG6 concentrations were significantly reduced (P < 0.001). No significant correlation was observed between anti-TG6 and anti-TG2 serum concentrations.

Conclusions: Anti-TG6 are more prevalent in children with untreated CD in the absence of overt neurological disorders. The synthesis of the anti-TG6 is related to a longer exposure to gluten before the CD diagnosis, and the autoimmunity against TG6 is gluten dependent and disappeared during GFD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Case-Control Studies
  • Celiac Disease / complications
  • Celiac Disease / diagnosis
  • Celiac Disease / diet therapy
  • Celiac Disease / immunology*
  • Child
  • Child, Preschool
  • Delayed Diagnosis
  • Diet / adverse effects*
  • Diet, Gluten-Free
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Glutens / adverse effects*
  • Glutens / immunology
  • Humans
  • Infant
  • Isoantibodies / blood*
  • Male
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / etiology*
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Transglutaminases / immunology*
  • Treatment Outcome

Substances

  • Biomarkers
  • Isoantibodies
  • Glutens
  • TGM6 protein, human
  • Transglutaminases