How did this happen?

                                               JupiterImages (photograph); Jen Christiansen (photoillustration)

In this post I'm going to talk about the etiology and the pathophysiology of Celiac Disease. Etiology is the cause, or set of causes, of a disease or condition. Pathophysiology is the convergence of pathology and physiology. The former describes conditions observed during a disease state, while the latter is the biological discipline that describes mechanisms and processes operating within an organism. Pathophysiology seeks to explain the physiological processes or mechanisms whereby a condition develops and progresses. 

First off, the etiology of Celiac Disease. The sad fact of the matter is that the precise cause of Celiac Disease is not known. However correlation has been shown between people with many different factors. One of these is if an infant under three months of age is exposed to gluten. Another strong correlation is if an immediate family member also has Celiac Disease. Next, a major life event, pregnancy, surgery, or emotional stress in people who are genetically predisposed will have a greater risk of developing Celiac Disease. In addition, those individuals with type 1 diabetes, thyroid disease, or other autoimmune diseases will have a greater chance of also obtaining Celiac Disease. Finally, if a person has a genetic disorder such as Down syndrome or Turner syndrome, they as well may have a higher risk of Celiac Disease developing.

The pathophysiology of Celiac Disease is that it's a multi-factorial and a multi-system disorder involving a genetic predisposition, environmental exposure of the small bowel mucosa to gluten, and an immunologic response to gluten.

Genetically, the majority (>90%) of people with Celiac Disease possess the HLA DQ2 haplotype, and 5% to 10% possess the DQ8 haplotype, conferring a negative predictive value greater than 98%. These haplotypes are encoded within the HLA class II region of the major histocompatibility complex on chromosome 6p. However, about 40% of the general population carries these haplotypes without having the disease, which makes their presence necessary but not sufficient for its development.

Environmentally there was a serendipitous observation that children with Celiac Disease improved during World War II when cereals used to make bread were scarce, and they relapsed after the war when the supply of these cereals was reinstituted. Risk for developing Celiac Disease is increased with the introduction of gluten in the diet of infants before the age of 4 months. Grains that activate the disease contain proteins that can form gluten (prolamins: glutenins and gliadins) and include wheat, barley, and rye. Grains that do not activate the disease include rice, corn, sorghum, and millet. Oats contain a very small proportion of prolamins and should be avoided initially.

Finally, with regards to immunology, exposure of the upper small bowel mucosa to gluten in susceptible people precipitates an immune mediated reaction that involves both the innate and the adaptive immune responses. Tissue trans-glutaminase, an enzyme present in the lamina propria of the small bowel, deamidates glutamine residues in gluten to form glutamic acid. Glutamic acid is a negatively charged molecule that is recognized by the antigen-precipitating cells that express the HLA DQ2/DQ8 receptors for T lymphocytes. T lymphocytes become activated and they begin to divide rapidly and secrete several immunomodulators such as immunoglobulins, cytokines, interferons, tumor necrosis factor, and interleukin 15 and 17 that cause damage to the enterocytes and result in villous atrophy.

I hope that by reading this you'll have come to understand a bit more about how it was possible for you or your loved one to develop Celiac Disease. In my next blog post I'll explain a bit more about how Celiac Disease is diagnosed. See you there!