An exploration of Glo-3A antibody levels in children at increased risk for type 1 diabetes mellitus

Abstract

Aims-To determine whether Glb1 homologue antibodies are associated with islet autoimmunity (IA) in children at increased risk for type 1 diabetes (T1D), and to investigate their relation with putative environmental correlates of T1D.Methods-We selected a sample from the Diabetes Autoimmunity Study in the Young (DAISY), a prospective study of children at increased risk for T1D. Cases were those who were positive for insulin, glutamic acid decarboxylase (GAD), or insulinoma-associated antigen-2 (IA-2) autoantibodies on two consecutive visits and either diagnosed with diabetes mellitus or still autoantibody positive when selected. Controls were from the same increased risk group, of similar age as the cases but negative for autoantibodies. Sera from 91 IA cases and 82 controls were analyzed in a blinded manner for immunoglobulin G (IgG) antibodies to Glb1 homologue by ELISA.Results-Adjusting for family history of T1D and HLA-DR4 positivity, Glb1 homologue antibodies were not associated with IA case status (OR: 1.01, 95% CI: 0.99 -1.03). Adjusting for age, family history of T1D, and HLA-DR4 positivity, Glb1 homologue antibody levels were inversely associated with breast-feeding duration (beta = −0.08, p = 0.001) and directly associated with current intake of foods containing gluten (beta = 0.24, p = 0.007) in IA cases but not in controls. Zonulin, a biomarker of gut permeability, was directly associated with Glb1 homologue antibody levels in cases (beta = 0.73, p = 0.003) but not in controls.Conclusion-Differences in correlates of Glb1 antibodies in IA cases and controls suggest an underlying difference in mucosal immune response.

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

“…T1D patients have antibodies against different wheat proteins in the absence of CD. 48,49 Although it could be taken as a secondary phenomenon related to increased intestinal permeability, recent studies concerning immunological crossreactivity between wheat proteins and self-proteins in T1D 50 suggest that autoimmune reactions to unknown antigenic proteins in intestinal mucosa might also be involved in small-bowel mucosa destruction in some T1D patients.…”

Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer

“…These comprise autoimmune diseases, including T1D (107,117,149,163), CD (45,46,51,126), multiple sclerosis (124,176,184), and rheumatoid arthritis (52), in which intestinal TJs allow the passage of antigens from the intestinal milieau, challenging the immune system to produce an immune response that can target any organ or tissue in genetically predisposed individuals (1,13,57,58,70,151). TJs are also involved in cancer development, infections, and allergies (32,55,57,147).…”

“…More recently, we reported a direct link between antibodies to Glo-3a (a wheat-related protein), zonulin upregulation, and islet autoimmunity (IA) in children at increased risk for T1D (148). Sera from 91 IA positive cases and 82 controls were analyzed.…”

Environmental Factors and Type 1 Diabetes Mellitus in Pediatric Age Group

“…Simpson et al compared the levels of antibodies to a wheat storage globulin homologue of Glo-3A, which is a non-gluten component of the wheat protein matrix. They have shown that in children with islet auto-immunity, the antibody titer was directly linked to the early introduction of gluten, and inversely to breastfeeding duration [87]. Not all authors agree with this association; a prospective analysis from the DIPP study did not show a correlation between early or late introduction of gluten and subsequent development of pancreatic β-cells autoimmunity [88].…”