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International Journal of Celiac Disease. 2024, 12(1), 1-11
DOI: 10.12691/ijcd-12-1-1
Open AccessReview Article

Toward an Etiology of Celiac Disease

Simon H Williams1,

1Independent researcher

Pub. Date: December 22, 2024
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Cite this paper:
Simon H Williams. Toward an Etiology of Celiac Disease. International Journal of Celiac Disease. 2024; 12(1):1-11. doi: 10.12691/ijcd-12-1-1

Abstract

The review proposes a model of the etiology of celiac disease. It describes how an enteroviral attack by a lytic virus leads to hyper-extracellular Transglutaminase 2, Tg2, evident at all stages of the disease by the presence of anti-tTG. The demand for Tg2 is supplied by both the cell and the lytic virus. The demand leads to excess Tg2 passing through the cell wall, excess ingress of Ca2+, the destruction of the mitochondria by Ca2+, and pyroptosis of the cell. The increase in extracellular Tg2 during the cell's life and following pyroptosis has two effects. First, it binds a C1r inhibitor to the vascular wall, preventing C1r-LP from converting prehaptoglobin (zonulin) into haptoglobin, causing the weakening of the tight junctions among the epithelial cells and allowing the entry of extraneous luminal materials and particularly the access of Tg2 arterial and luminal, as it is now open directly to the lumen and the mesenchyme structure. It is this Tg2 that damages the villus structure as the Tg2 binds fibronectin into the mesenchyme, causing scarring, shrinkage, and turning the villi into the rigid scarred structures characteristic of CD. The model suggests why CD is a chronic lifelong disease reactivated upon the resumption of gluten consumption. A discussion of Non-Celiac Gluten Sensitivity and Refractory CD follows. The paper explains how extracellular transglutaminase causes zonulin and damages the extracellular membrane. Thus, zonulin is a symptom, not a cause. Notably, the paper demonstrates that the basic tenet of autoimmune diseases, that the cells destroy themselves, is incorrect, at least for CD. Applying this etiology to other conditions may be relevant because of the almost universal glutaminolysis in cells and the substantial amount of Gluten in modern diets.

Keywords:
Celiac Non-Celiac Gluten Sensitivity NCGS Refractory Coxsackie virus Transglutaminase Gluten Villus Apoptosis Pyroptosis

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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rejection rate =

10%
Manuscript template