Celiac Disease and Beyond: Gluten and the Immune System

Christine Doherty, ND

Celiac disease is one of the most commonly misdiagnosed diseases in the country. One in 130 Americans have celiac disease, yet it currently takes a person about nine years of seeking medical care to get a correct diagnosis. It is a chameleon disease in that it can look like so many other conditions: diabetes, osteoporosis, anemia, etc. … but often, even when people have classic celiac disease symptoms like diarrhea and weight loss, they test negative for celiac.

Despite testing negative for celiac disease, many millions have wheat allergies or intolerance that respond to a gluten-free diet. Approximately 2.8 million people have celiac disease in the U.S., more than 90% of which are still un- or misdiagnosed. Approximately 6 million people have IgE to wheat; and between 25-40 million are gluten intolerant. Internationally, 8,000 people are being diagnosed with celiac disease every month. Current research is beginning to shed light on some of the mechanisms of wheat allergy, gluten intolerance and celiac disease.

Diagnosing Celiac Disease

Celiac is a triad diagnosis: The first step is the serology; the second step an endoscopic biopsy; and the third step is the response to the gluten-free diet.

The serologic tests are: tissue transglutaminase IgA (TTG IgA), anti-endomysial IgA (EMA), total IgA (as 4% of celiacs have IgA deficiency) and antigliaden IgG and IgA. Many laboratories offer a celiac panel with TTG IgA as a primary test with a reflex EMA. The antigliaden antibodies have not been as specific or sensitive as the TTG IgA test, and so have been controversial as screening tests. The next generation of this test has been developed with much higher sensitivity and specificity.

The current “gold standard” for celiac diagnosis also includes a multi-sample, small intestinal biopsy read by a pathologist who is knowledgeable about the staging of celiac disease and intraepithelial lymphocyte testing. Celiac is not just total villous atrophy but may manifest as normal villous architecture with increased intraepithelial lymphocytes and anything in between. At a recent lecture by Peter Green, MD, head of the Celiac Disease Center at Columbia University, he stated that the Center changes the diagnosis from negative to positive on 20% of the endoscopic biopsies they review for second opinions. This strikes me as a problem for the “gold standard test,” which clearly is not all that sensitive or accurate compared with the serologic tests, which all boast sensitivities and specificities in the high 90% range. The classic pathology changes of celiac disease in the small bowel improve or reverse after gluten is removed from the diet. If a person is gluten free, he or she has to be back on gluten for three months before getting an accurate biopsy.

Current Research

Research is being done at the University of Maryland on zonulin, an endogenous signaling protein that seems to be central in the pathogenesis of celiac disease and a breakthrough in the understanding of leaky gut syndrome. Not only does zonulin increase paracellular transport in the gut, but it also increases permeability of the blood-brain barrier and in the lining of the lungs. So far, much of the research on zonulin has been focused on the study of celiac disease and Type I diabetes mellitus. One of the studies showed that gliadin activated zonulin signaling to increase intestinal permeability to macromolecules, even when the primary celiac genes, HLA DQ2 and DQ8, were not present. Could this be one of the mechanisms of gluten intolerance? In a follow-up study, researchers incubated the sample with a high-dose probiotic formula containing 450 billion organisms per dose, and they found the probiotics downregulated the gliaden effect on zonulin, which is scientific evidence that probiotics improve leaky gut! The role of zonulin appears to be a response to a pathogen in the gastrointestinal tract.

Wheat Allergy/Intolerance

Wheat is one of the top IgE-mediated allergies, which causes digestive symptoms like nausea, vomiting and abdominal pain, as well as allergic rhinitis, urticaria, atopic eczema, angioedema and asthma. For people who work with flour, there is a type of asthma called baker’s asthma, where the immune system gets triggered through repeated inhalation of flour. Wheat is the most common cause of exercise-induced anaphylaxis. The new ImmunoCAP blood test for IgE appears to be a better choice than the radioallergosorbent test (RAST) or scratch test, and is available through most laboratories. The IgE reaction is more commonly to the albumin and globulin fractions of wheat and not to gliaden and gluten, although some patients have cross reactivity with rye and barley. I believe this antibody is responsible for many patients who are being labeled “gluten intolerant,” as approximately twice as many patients suffer from this allergy than from celiac disease.

Antigliaden IgG may be a sign of latent celiac disease or of a wheat allergy. Often, this will be the only positive test in a celiac panel, in which case most gastroenterologists will not perform a biopsy. I advocate a trial of the gluten-free diet, and this antibody is the only one that is accurate for testing for neurological complications of celiac, also known as CNS sprue. I sometimes run multi-food IgG panels, and if the gluten grains come up high, I follow it up with the celiac serology before implementing a gluten-free challenge. I feel this is important because if the patient has celiac it helps increase compliance to a strict, life-long, gluten-free diet and can lead to the diagnosis of family members. To further complicate matters, once patients are gluten free, even for a few weeks, the blood work for celiac is no longer accurate. Celiacs who are not gluten free are at a doubled risk of mortality, mostly from GI cancers. Within a year of going gluten free, their risk returns to normal. IgG allergy does not appear to have the same potentially fatal complications as celiac and IgE wheat allergies, but can show many of the same symptoms as celiac disease.

Gluten Intolerance

“Gluten intolerance” is a catchall term used to describe those who clearly feel better on a gluten-free diet, but many may have undiagnosed cases of celiac and/or wheat allergies. In many cases, people were denied testing because they did not have the “right” symptoms, according to their primary care practitioners. There are patients who have a gluten intolerance that is more like lactose intolerance. It is not immune mediated, but is more of a digestive issue. It is not yet clear: Is this an enzyme problem, or could it be a chemical reaction? These patients clearly respond clinically to a gluten-free diet. If we look to the animal world, many animals who eat wheat have four stomachs and chew their cud. It makes sense that if there is any digestive compromised, wheat would be too hard to break down effectively.

We are at the tip of the iceberg when it comes to identifying the effects of gluten on the human system. This already is a major trend in the food industry, with gluten-free specialty food expected to be a $4 billion market by 2008 in the U.S. alone. I firmly believe we are the perfect practitioners for these patients, with our knowledge of nutritional deficiencies, improving digestive function and our ability to think beyond medical specialties. We are also adept at seeing beyond classic celiac disease to identify individual presentations of these conditions.


DohertyChristine Doherty, ND graduated from Bastyr University in 1998. She is in private practice at Balance Point Natural Medicine in Milford, N.H., which she co-founded with her acupuncturist husband. Dr. Doherty is a medical advisor to the magazine Living Without, for people with food allergies, and is medical advisor to the Southern New Hampshire Gluten Intolerance Association. She also served on the N.H. osteoporosis advisory council from 2000 to 2003, and is a past vice president of the New Hampshire Association of Naturopathic Doctors. Dr. Doherty speaks on gluten-related topics nationally at lay and medical conferences, including the AANP, Gluten Intolerance Group, Teton Wellness Festival, and in January 2008 at CAM Expo East (renamed the Integrative Medicine Symposium). Watch for her book, Gluten free Vitality.

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