Anti-transglutaminase 6 autoantibody development in children with celiac disease correlates with duration of gluten exposure

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 suffering from 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 two groups (p=0.04). None of the CD-patients and of the controls testing positive for anti-TG6 were suffering from neurological disorders. Eleven/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