Celiac Disease and Non-Celiac Gluten Sensitivity
Understanding Celiac Disease
Much has been learned about how environmental and genetic factors interact with the immune system to inflame and damage the lining of the small intestine in celiac disease. The most important and best-characterized genetic components involved in the development of celiac disease are known as human leukocyte antigens (HLAs). More than 98% of people with celiac disease have at least one of two variants of a gene called HLA DQ. The HLA DQ2 variant of this gene is found in approximately 95% of celiac patients, while the HLA DQ8 variant is carried by the remainder. These genes play an integral role in priming the autoimmune response to gluten that occurs in celiac disease (Denham 2013; Sapone 2012; Green 2003).
Celiac disease is characterized by increased intestinal permeability (“leaky gut”), which allows gluten to seep through the compromised gut barrier and provoke a dysfunctional immune response (Fasano 2009; Fasano 2008; Lionetti 2011).
During this inflammatory immune assault against gluten, collateral damage to intestinal epithelial cells causes leakage of their contents into the fluid surrounding the cells. Included in this cellular discharge is a critical enzyme called tissue transglutaminase (Dieterich 1997; Fasano 2009). Tissue transglutaminase modifies the composition of the gliadin peptide, enabling gluten to bond strongly to the HLA DQ2 and DQ8 proteins. This then provokes an immune response from the T and B cells of the immune system and the production of antibodies against tissue transglutaminase (Lionetti 2011; Denham 2013; Fasano 2009).
The helper T cells of the immune system trigger the release of cytokines (signaling molecules), particularly interferon-gamma, which promote inflammation that specifically targets the lining of the small intestine, resulting in the autoimmune damage and flattening of the intestinal villi that are characteristic of celiac disease (Lionetti 2011; Kagnoff 2007; Denham 2013).
Nutrient absorption occurs in the small intestine, a tube roughly 20–22 feet long with an inner surface that, when magnified, appears wrinkled into hundreds of folds. Each fold is covered with thousands of fingerlike projections called villi (singular: villus). Each villus, in turn, is covered with thousands of tiny, tightly packed projections called microvilli. Together, the villi and microvilli increase the intestinal absorptive surface area 60–120 times (Helander 2014; CARTA 2015; CHP 2014). The villi also contain enzymes that help break down food particles to their smallest components: proteins into amino acids, and carbohydrates into simple sugars (Skovbjerg 1981; Nordström 1967).
In celiac disease, intestinal damage induced by the autoimmune reaction to gluten ingestion manifests as a flattening of the villi (a hallmark of celiac disease), which reduces the surface area available for nutrient absorption. The resulting malabsorption leads to both intestinal consequences such as indigestion and diarrhea, and non-intestinal consequences such as anemia and osteoporosis (Kagnoff 2007; Guandalini 2014; Lionetti 2011).
Wheat Allergy vs. Celiac Disease vs. Non-celiac Gluten Sensitivity
Wheat allergy, celiac disease, and gluten sensitivity are three separate conditions arising from distinct processes, though they may share certain signs and symptoms (UCLA Health 2015; ACDA 2015a). The conventional medical definition of wheat or gluten allergy refers to a less common condition that affects about 0.4–0.5% of the general population and which classically involves Immunoglobulin E (IgE) antibodies to wheat proteins, including gluten (Sapone 2012; Catassi 2013; Lundin 2012; Volta 2013). IgE antibodies play a central role in immediate food allergy reactions, the kind that usually occur within minutes to several hours after ingesting the allergenic food, though the reaction can occur up to two days later (Katta 2014). An allergy involves the release of histamine and other inflammatory substances and can cause serious symptoms such as skin eruptions, runny nose, itching, tearing, coughing, and in rare cases, anaphylaxis and even death (Matsumura 1994; Sapone 2012). IgE reactions to foods can be measured by blood or dermal testing (FARE 2015b; FARE 2015c).
Celiac disease is an autoimmune disease, not an allergy. Whereas allergic reactions tend to be transitory, appearing and disappearing within minutes to hours after contact with an allergen such as wheat, the autoimmune reactions of celiac disease are enduring and highly destructive. Recovery of the normal structure of the intestinal lining takes 6–24 months of adherence to a strict gluten-free diet (Ferri 2015; Mayo Clinic 2014; UCLA Health 2015; ACDA 2015a).
Non-celiac gluten sensitivity refers to a more recently-recognized condition characterized primarily by a beneficial response to dietary elimination of wheat-containing foods for people in whom celiac disease and classical IgE-mediated wheat allergy have been ruled out. Whereas wheat or gluten allergy and celiac disease are well-defined conditions, science still has much to learn about non-celiac gluten sensitivity, including the mechanisms underlying the condition and how best to diagnose it. Non-celiac gluten sensitivity is neither an autoimmune condition nor a classical allergic condition characterized by rapid IgE-mediated reactions (UCLA Health 2015; Sapone 2012). One study found that over half of non-celiac gluten sensitivity patients tested positive for antigliadin immunoglobulin G (IgG) antibodies, and some researchers consider IgG antigliadin antibody testing useful in identifying cases of non-celiac gluten sensitivity (Volta, Tovoli 2012; Mansueto 2014). A recent clinical study suggests gluten or other proteins in wheat and related grains may not be the sole cause of non-celiac reactivity to wheat. In some people, fermentable, oligo-, di-, monosaccharides, and polyols (FODMAPs), which are poorly absorbed carbohydrates, may contribute to sensitivity reactions to wheat among people without overt celiac disease or wheat allergy (Biesiekierski 2013).
Table 1: Comparison of Wheat Allergy, Celiac Disease, and Non-celiac Gluten Sensitivity
(UCLA Health 2015; Ferri 2015; Sapone 2012; FARE 2015a)
More general information about food allergies and food sensitivities is available in the Life Extension Magazine article titled What’s Really Making You Sick?