Celiac disease (CD) may be considered the most common chronic inflammatory condition with an estimated incidence in Western Countries around one per cent. CD is an autoimmune pathology of the intestine caused by an abnormal immune response to dietary gluten that occurs in genetically susceptible individuals . The well known genetic factor is the HLA-DQ region at 6p21.3 which, contributes no more than 40% of the risk with the non-HLA genes seeming to be playing a stronger determinant of CD susceptibility
The immune response occurs when increased amounts of gluten peptides can enter the intestinal mucosa to initiate the inflammatory cascade. The actual mechanism by which the peptides are transported is still not clear, but may involve a faulty mechanisms with secretory IgA. (see references 3,4)
It currently appears that different gluten peptides are involved in the disease process in a different manner, some fragments being ‘toxic’ and others ‘immunogenic’. Those defined as ‘toxic’ are able to induce mucosal damage and those defined as ‘immunogenic’ are able to specifically stimulate HLA-DQ2- or DQ8.
Two pathways have been hypothesized to be triggered by these peptides: one is the direct effect on the epithelium that involves the innate immune response the non-specific immune system, the other represents the adaptive immune response involving CD4+ T cells in the lamina propria that recognize processed gluten antigenic detrminants.
Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin isi a 47-kDa inflammatory protein that was discovered in 2000 by Alessio Fasano and his team at the University of Maryland School of Medicine. The protein helps regulate leakiness in the gut by opening and closing the spaces or "junctions" between cells in the lining of the digestive tract. Zonulin has been shown to be upregulated in several autoimmune diseases, including celiac disease (CD) and type 1 diabetes (T1D), in which TJ dysfunction seems to be the primary defect (see References 5,6)
It appears that gluten may be a strong trigger of zonulin in some individuals. And since no human can completely digest gluten, this may present a problem for some individuals who present a zonulin response to gluten. (See References 5,6) In additon Zonulin, is found in higher levels in the blood of both celiac and non-celiac gluten-sensitive individuals,
Larazotide acetate, (Alba Therapuetics) is a drug currently in development that works by inhibiting zonulin, which has been shown to increase the permeability of the gut in celiac disease, allowing gluten particles to pass through to trigger inflammation, and gastrointestinal and other symptoms. Larazotide acetate is a novel agent that belongs to a new class of drugs called tight junction regulators.
The lining of the intestines have small areas called villi which project outward into the opening of the intestine. These structures help absorb nutrients. When people with celiac disease eat foods with gluten, their immune system reacts by damaging the villi. Because of the damage, the villi are unable to properly absorb iron, vitamins, and other nutrients.As a result, a number of symptoms and health problems may occur.
Gluten Inflammation in Other Diseases
According to Amy Meyers MD., If you have Lupus, Rheumatoid Arthritis, Hashimoto’s, Multiple Sclerosis, or any other autoimmune disease you should not be eating gluten.. "The bottom line is that if you have an autoimmune disease, or any inflammatory condition, you shouldn’t be eating gluten, period.."
According to Dr Meyers: "When your immune system is continuously creating inflammation in response to the gluten you’re eating, your leaky gut, and the microbes and toxins flooding your bloodstream, you develop chronic inflammation. Your immune system is now stressed and is less able to attack pathogens and invaders with precision. Instead, it begins indiscriminately sending wave after wave of attack in a desperate attempt to fight off the invaders. Eventually, your body’s own tissues end up on the receiving end of the attack, and you end up with an autoimmune disease..." read the full article Reference 7).
Gluten is a protein found in wheat. What part of the wheat grain is it located? How can you identify foods that contain gluten? ... read more.What are the genes in the Human Genome responsible for Celiac Disease?
There are two genes that are responsible for Celiac disease although other genes and environmental factors play a role in those that get the disease, since as many as 30-40% of the population may have the gene(s) but not show symptoms... read more.Why is an immune response triggered against gluten in some individuals?
How does gluten cause celiac disease?... read moreWhat is the difference between celiac disease and gluten sensitivity?
Only 1% percent of the population has true Celiac disease. Many more have what is know as gluten sensitivity What is the difference between the two, and how to know which one you have... read more. Is gluten the only substance in wheat people are sensitive to? ... read more.What are the ongoing Clinical Trials for Celiac Disease
There is still a lot that is not understood about how gluten's affect humans... many clinical trials are underway... read moreWhat are lectins -why are they toxic and cause illness?
Both plants and animals contain lectins. What are they and why can they be very toxic to our bodies. Why do beans have to be soaked and properly cooked? What is the role of lectins in autoimmune disease? ...read moreRole of Lectins in Inflammation
Although gluten has been in the limelight for sometime, many people may not realize that other lectins may be causing digestive issues... read more