Figure 6. Proposed disease model.

Illustrating a possible scenario for disease development. Genetic variation contributing susceptibility to disease can be found in at least four, somewhat overlapping, biological functions. The result is an “overload” or imbalance of proline vs glutamine. Due to the abundance of proline within the extracellular matrix (ECM) as well as in gluten, the proline from gluten is interpreted as degradation of ECM. When the body is not starving, the ECM is normally not degraded, unless there is a pathogen attempting to break through this barrier. The immune system mounts an attack against an invasive “phantom pathogen” which is believed to degrade the ECM. When proline is catabolized, reactive oxygen species (ROS) are released. In order to start re-building and crosslinking ECM molecules, Tissue transglutaminase (TGM2) expression is up-regulated by TNFα which in turn is stimulated by DUSP10 and Protor-2 (PRR5L). This rebuilding of the ECM counteracts the degradation by the imagined pathogen. However, the phantom pathogen remains and the adaptive immunity is brought in. Searching for antigens, it finds an abundance of TGM2 beside the ECM and forms antibodies against its own soldier. Some susceptibility genes can be found in the center of this model and some can be found within the spiral. Genes like HLADQ and other genes from the adaptive immunity are likely to be found in the spiral.