Celiac disease

It’s becoming more and more common to see things like “gluten-free pizza” or “gluten-free buns” and other gluten-free items at restaurants, grocery stores, or other food-based businesses. This is partly because there’s this increasing recognition, awareness, and diagnosis of a disease called Celiac Disease, in the past called celiac sprue. As many as 1 in 100 people have Celiac disease although many remain undiagnosed.

Now, Celiac disease is currently understood as an immune system-mediated disorder, where the gluten in food triggers the body’s immune cells to attack the cells in the small intestine as well as produce auto-antibodies against tissue transglutaminase also found in the small intestine as well as other tissues like the heart or the liver.

Gluten’s found in common wheats and grains, including wheat, rye and barley. If we take a look at wheat, you’ve got your individual wheat kernels, and then inside each kernel there is the endosperm, which has a bunch of nutrients for the seed’s embryo, mostly protein and starch, and some vitamins. The type of protein here is gluten, the main culprit in celiac disease.

Well, really the main culprit behind celiac disease is gliadin, an umbrella term given to a group of gluten peptides that share a 33 amino-acid sequence which triggers an immune response. So, if somebody with celiac disease eats a wheat-based pizza, it’s broken down in the stomach into gluten peptides ...and a whole lot of other stuff.

That other stuff is no challenge for digestion - gluten peptides, like the gliadin in wheat, however, are high in proline and glutamine, two amino acids which make it a tough little bugger to digest.

So when the undigested gluten proteins, like gliadin, get to the small intestine, they meet the intestinal mucosa, which is lined with a layer of intestinal epithelial cells. Gluten proteins can then get across the gut epithelial cells, either between them, or through the cell, from the apical to the basolateral membrane, and get to the lamina propria, which is a thin layer that lines the gut wall.

Once there, an enzyme called tissue transglutaminase, or tTG, cuts off of an amide group from the protein. Deamidated gluten proteins are then eaten up by macrophages and served up on its MHC class II molecules.

Remember, macrophages are in the gut and are always doing a bit of “gut sampling” where they grab proteins (which a lot of times are from foods that we’ve eaten) and show them to the immune cells.