Gluten: What is all the fuss about? Part 1

John J. Zone, MD

Dr Zone has been studying gluten since the 1970s. He comments that recently, all we hear about is gluten sensitivity and gluten free diets. In fact, there are entire sections in the supermarket that are dedicated to gluten sensitivity. This used to be considered rare and now, it appears, that everyone has it.  There are now improved methods for diagnosing celiac disease and so the number of people diagnosed has increased.  However, there is also a population of people who have self diagnosed gluten sensitivity.

What is gluten?

Gluten is a group of proteins from grains that are insoluble in water. It is made up of prolamins and glutelin. Prolamins are high in proline, alcohol soluble, and monomeric. Glutelin, which we know less about, is soluble in dilute acid or alkali and is comprised of aggregated polymers. Dr Zone mentions that the initial studies feeding people various fractions of gluten were conducted during the 1950s and 1960s, prior to IRBs, “we could feed people a lot of things that we can’t feed people now” and they found that a particular fraction of gluten, the prolamins, were toxic. (The glutelin fraction was never studied) Existing prolamins include gliadin (wheat), hordein (barley), and secalin (rye), all of which may induce celiac disease. Glutenin (wheat), which is a glutelin, may be pathogenic in celiac disease, but this has not yet been confirmed.

Wheat Allergy

In dermatology, we don’t always think about food-induced allergies. Wheat allergy is IgE mediated, i.e., crosslinking of IgE molecules bound to basophils and mast cells. It is repeat sequences in gluten peptides, e.g., serine-glutamine-glutamine-glutamine-glutamine-proline-proline-phenylalanine—not necessarily gliadin. This subsequently releases chemical mediators such as histamine.



The reason why patients with urticaria don’t always respond to anti-histamines is because they are also releasing TNF, proteases, heparin, and IL-5. This is why some people with urticaria will get better with TNF inhibitors.

Wheat Dependent Exercise Induced Anaphylaxis

Dr Zone has seen this on two occasions and it can be quite dramatic. One of his patients had a severe reaction after exercising and they deduced that it occurred because he had eaten gluten; as he didn’t eat  gluten before execising, he could continue playing squash. This is caused by omega gliadin and the way to test for this is through a skin test or challenge.

Celiac Disease

Celiac disease is also known as gluten sensitive enteropathy, celiac sprue, and non-tropical sprue. One in 100 Caucasian Americans do have celiac disease. This is an HLA-associated disease. 90 percent of celiac disease and DH patients express HLA DQ2; 9 percent express DQ8. 20-25 percent of Caucasians have DQ2 or DQ8. The receptors coded by the HLA genes are essential for the processing of the gliadin antigen in celiac disease. So if you think about the people out there buying gluten-free foods, 20-25 percent of them have the gene makeup to process the gliadin antigen and develop an immune response.  So, essentially, lsss than 5% of the people with the correct HLA genes will develop clinical celiac disease, others may have silent or latent celiac disease and some healthy individuals have all of the genetic makeup to develop celiac disease, yet they will never get it.

It’s important to remember that celiac disease clusters with other autoimmune disorders such as Addison’s disease, autoimmune thyroiditis, atrophic gastritis, SLE, RA, myasthenia gravis, and vitiligo. The interesting thing about this is that we know the antigen that precipitates the autoimmunity. Celiac disease is also common in Down’s syndrome.

Celiac Immuno


Dr Zone comments that it is a “huge mistake” to go on a gluten free diet without first being tested for celiac disease.  There is range of pathology in celiac disease that can be seen by proximal small intestinal mucosal immunopathology. Dr Zone also states that he and many of his colleagues were taught that to have celiac disease, you have to have a bloated abdomen, be malnourished and short and skinny…this is how it was described in the past.

What is celiac disease?

Celiac disease is an inflammatory injury of the small intestinal mucosa after ingestion of gluten in wheat, rye, or barley. We can see improvement once gluten is withdrawn from the diet. It is important to remember that many patients with histological inflammation have atypical intestinal symptoms or no symptoms at all. Clinical studies have shown that only 15-20 percent of CD and DH patients identified by serology and confirmed by biopsy have classical symptoms of diarrhea and malabsorption.

So how do you diagnose celiac disease? IgA tissue transglutminase (TG2) is the hallmark of celiac disease and correlates with the severity of intestinal inflammation.  A 2003 study looked at the prevalence of CD in the United States based on IgA tTG testing of serum found the following ratios:

  • 1:133 in not at risk individuals
  • 1:56 in symptomatic patients
  • 1:39 in second degree relatives
  • 1:22 in first degree relatives

This demonstrates that CD is common, and not rare. (Fasano et al: Prevalence of Celiac Disease in at Risk and Not at Risk Groups in the United States. Arch Intern Med. 2003; 163: 286 – 292)


Celiac disease is as common as psoriasis and can be found in one to two percent of the Caucasian population. CD profoundly affects the immune system, which is the modulator for inflammatory skin disease.

It is important to remember that most celiac patients have few or no symptoms at all. There is a wide range of intestinal abnormality and the high risk genotype is essential for pathogenesis.