Antibodies to the Wheat Storage Globulin Glo‐3A in Children Before and at Diagnosis of Celiac Disease

Abstract

Celiac disease (CD) is an autoimmune disease triggered by exposure to gluten-containing foods. IgA autoantibodies to tissue transglutaminase (TTG) are elevated in CD, but little is known about the gastrointestinal state before the appearance of TTG. Antibodies to wheat storage globulin Glo-3A have been studied in type 1 diabetes, and may be a marker of altered mucosal barrier and/or immune function. In the present study, we investigated antibody responses to Glo-3A in CD. In the Diabetes Autoimmunity Study in the Young, children were studied prospectively from birth for the appearance of TTG and CD. Fifty cases of CD were frequency matched with 50 controls on age (of TTG seroconversion in the case), sex, ethnicity, presence of a first-degree relative with type 1 diabetes mellitus, and human leukocyte antigen -DR3 genotype. In cases and controls, IgG antibodies to Glo-3A were analyzed in a blinded manner in the sample collected at the time of seroconversion to TTG positivity (or the matched sample in controls) and in all of the previous samples since birth (mean 4.5 samples). The association between Glo-3A antibody levels and CD case status was explored using t tests at the TTG-positive visit and when Glo-3A levels were highest, and mixed modeling to describe Glo-3A over time. At the time of first elevated TTG (mean 4.9 years), patients with CD had higher Glo-3A antibody levels than controls (13.3 ± 17.2 vs 7.6 ± 11.7, P = 0.005). In both cases and controls, Glo-3A antibodies appear to peak at a mean age of 2.9 years, before mean age of initial TTG seroconversion. The peak Glo-3A antibody levels were higher in cases than controls (25.5 ± 21.8 vs 14.9 ± 18.3 P = 0.0007). Using mixed modeling to account for multiple visits per person, cases had higher levels of Glo-3A antibodies than controls at all ages from birth to TTG seroconversion (β = 0.53, P = 0.002). Compared with controls, CD cases have higher Glo-3A antibody responses in the beginning years, before initial detection of TTG.