Special Considerations in Children and Young Adults with Celiac Disease

Abstract

Celiac disease is a prevalent disorder precipitated by ingestion of cereal gluten proteins. The disease has many autoimmune features including autoantibodies to the enzyme transglutaminase 2. Several genes and environment are implicated in the disease development process. HLA is the single most important gene, and gluten is obviously an important environmental factor. Many details as to why certain HLA molecules (DQ2 and DQ8) predispose to the disease have been mapped. This involves deamidation of gluten peptides by transglutaminase 2, improved binding of post-translationally modified gluten peptides to the disease-associated HLA molecules, and recognition of modified gluten peptides by interferon-γ producing CD4+ T cells. Damage of enterocytes in the gut lesion involves autoaggressive CD8+ T cells that employ natural killer cell receptors for recognition of stress-induced ligands. The mechanism for generation of the anti-transglutaminase 2 reactive antibodies is not fully understood, but it likely involves B cell help from gluten-reactive CD4+ T cells. The disease serves as a good model for other autoimmune disorders.