Celiac disease onset and inflammatory milieu

Figure 1 Examples of exogenous factors contributing to inflammation leading to celiac disease. These factors act to increase inflammation, dysbiosis, and epigenetic changes. All contribute to increased intestinal permeability.

Figure 2 The intestinal barrier and factors causing its disruption. Both the mucus layer and tight junctions between cells contribute to a healthy barrier. However, disruption in the mucus layer and tight junctions between cells will result in increased intestinal permeability.

Figure 3 Molecular-level steps by which gluten is recognized as antigenic in celiac disease. Gluten from wheat, rye, or barley is broken down into gluten peptides. Tissue transglutaminase deaminates them, triggering a cascade that leads to intestinal villous atrophy. HLA: Human leukocyte antigens; APC: Antigen-presenting cell; IFN-γ: Interferon-γ; IL: Interleukin.

Figure 4 Stages in the pathogenic change from normal to the celiac disease state. The description of these stages is provided in the text. At each subsequent stage, the window for prevention of celiac disease onset/reversibility is diminished. HLA: Human leukocyte antigens; CD: Celiac disease.

Figure 5 A model of celiac disease onset. The top panel shows that various combinations of inflammatory load thresholds for the quantitative/affinity vs loss of tolerance models may occur. As inflammatory load increases in the tolerant individual (lower panel), regardless of the threshold levels (top panel) the balance will be tipped toward disease onset, so that oral tolerance may be breached.

Figure 6 Examples of metrics that can be used to gauge immunologic response in celiac disease onset. Such metrics act as confirmatory measures when developing an inflammatory load equation. AI: Artificial intelligence.