Celiac.com 02/01/2020 - Traditionally, gluten is defined as a cohesive, elastic protein that remains when starch is rinsed from wheat flour dough. Gluten is the stuff that makes bread soft and pliable. It's the stuff that makes wheat paste sticky. It's also what causes so much trouble for people with celiac disease. Here are some quick facts about gluten and gliadin.

Gluten is actually made up of many different proteins. During digestion, the gut breaks down both gliadin and glutenin proteins into smaller units, called peptides, polypeptides or peptide chains. These peptide chains are made up of strings of amino acids--very much like beads on a string. 

Gluten Triggers Immune Reaction in Celiac Disease

Only wheat contains true gluten. However, rye and barley contain proteins that are similar enough to gluten to cause an immune reaction in people with celiac disease. Oat proteins have similar, but slightly different polypeptide chains and may or may not be harmful to celiac patients. There is scientific evidence supporting both possibilities.

There are two main types of proteins in gluten: gliadin and glutenin. 

While there are differences between the two, the main thing they have in common is that they trigger an autoimmune reaction in people with celiac disease. 

One peptide in particular triggers an adverse reaction in celiac patients when introduced directly into the small intestine. This peptide includes 19 amino acids strung together in a specific sequence. Although the likelihood that this particular peptide is harmful is strong, other peptides may also be harmful, including some derived from glutenin.

What Does it Mean to Be Gluten-Free?

When celiac patients talk about eating "gluten-free" or a following a "gluten-free diet," they are really just talking about avoiding the harmful peptides from wheat, rye, barley, and possibly oats. 

This means eliminating all foods and ingredients made from these wheat, rye, barley, such as food starch prepared from wheat, and malt made from barley, even if these foods don't contain gluten in the strict sense. 

So, going "gluten-free" has become shorthand for avoiding unsafe foods and ingredients that can harm people with celiac disease or gluten-intolerance, and eating foods and ingredients that are safe.

Corn and Rice Do Not Contain Gluten

In recent years, especially among non-celiacs, the term gluten has been stretched to include corn proteins (corn gluten), and there is a glutinous rice, although in the latter case, glutinous refers to the stickiness of the rice rather than to its containing gluten. 

Both corn and glutinous rice are safe for people with celiac disease.

The condition is related to IgA deposits under the skin. These occur as a result of ingesting gluten. These deposits take a long time to clear up, even when the patient is on a gluten-free diet.

While most individuals with DH do not have obvious GI symptoms, almost all have some damage in their intestine. They have the potential for all of the nutritional complications of celiac disease. It is believed by some GI professionals that most DH patients do indeed have celiac disease.

It is unusual to develop DH after a celiac patient starts a gluten-free diet. About 5% of celiac patients will develop DH, either before being diagnosed or within the first year on the diet. The fact that DH can develop even after starting the diet is probably due to the long lasting nature of the IgA deposits.

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The traditional approach to diagnosing celiac disease is a three-step process:

• Perform a biopsy of the lining of the small intestine. This is a surprisingly easy procedure which takes only a few minutes, although small children are usually sedated first, which adds to the cost and complexity of the biopsy. If the villi are damaged (flattened or atrophied mucosa), go to step 2.
• Place the patient on a gluten-free diet for six months or longer and then perform another biopsy. If the villi are healed, go to step 3.
• Put gluten back in the diet for six months or longer, and then perform a third biopsy. If the villi are again damaged, then the diagnosis is complete. At this point, the patient goes on a gluten-free diet for life.

Many doctors now feel that step number three is unnecessary, and some feel that even the second biopsy may be unnecessary. Part of the reason for this change in thinking is the development of three useful antibody blood tests: endomysial, reticulin (IgA), and gliadin (IgG and IgA). If the patient has been eating gluten regularly and all three tests come back positive, there is a very high chance that the patient has celiac disease. If all three tests come back negative, then it is very likely that the patient does not have celiac disease. Mixed results, which often occur, are inconclusive.

All of the laboratory tests that can be performed are strongly affected by a gluten-free diet. Tests will return negatives if the individual has been on a gluten-free diet for some time, and there is much debate about the length of time a patient must return to a gluten-laden diet before being tested. It probably depends on many factors: the level of damage that was done before starting a gluten-free diet, the length of time the person has been gluten-free, the amount of healing that has occurred, and the sensitivity of the individual to gluten.

A tentative diagnosis of celiac sprue is usually offered if the patients symptoms clear up after some time on a gluten-free diet. This is often followed by a "challenge" in which one of the offending grains (usually wheat) is eaten to see if the symptoms reoccur. However, this approach is much less desirable than having a firm diagnosis from a combination of antibody tests and one or more biopsies.

Because a gluten-free diet precludes accurate testing, if you suspect celiac disease, it is advisable to have diagnostic tests performed before starting a gluten-free diet.

Some physicians will accept positive antibody tests, one biopsy, and improvement on a gluten-free diet as sufficient for diagnosing celiac disease. Many other doctors prefer to perform a second biopsy, feeling that if it shows normal villi after a period of eating gluten-free then the diagnosis is confirmed. There are still some doctors who prefer the three-step approach mentioned above, though most view this as unnecessary.

Take, for example, buckwheat. Along with corn and rice, this is one of only three common grains left on the "safe" list for celiacs. However, some celiac societies have put it on the "unsafe" list and there is anecdotal evidence that some individuals react to it as they do to wheat. Yet a well-known specialist in grain research points out that buckwheat is more closely related to rhubarb than to the toxic grains, so if buckwheat is unsafe then any plant might be unsafe.

In considering anecdotal evidence for whether a food is safe or not, individuals must make their own choices, but each of us should clearly understand that anecdotal evidence is gathered from individuals with widely varied experience.

It could be that the "buckwheat flour" that a celiac reacted to was actually one of those mixes that combines buckwheat flour with wheat flour. Another possibility is that, since buckwheat and wheat are often grown in the same fields in alternating years, the "pure buckwheat flour" may have been contaminated from the start by wheat grains gathered at harvest. Yet another explanation might be that the buckwheat was milled in a run that was preceded by wheat or any of the other toxic grains, so the flour was contaminated at the mill. Finally, some individuals -- celiacs or not -- may have celiac-like reactions to buckwheat; they are allergic. Celiacs who are allergic to buckwheat may be easily fooled into believing they are having a gluten reaction. Or, it could be that some evolutionary trick has put a toxic peptide chain into buckwheat despite its distant relation to the other grains, but the odds against this happening are long.

As individual celiacs learn to live gluten-free, they must gauge their own reactions to foods, do lots of research, ask questions, and try to understand the many variables that may affect the ingredients in their food.

The following is a list of ingredients which some celiacs believe are harmful, others feel are safe:

• Alcohol
• Grain alcohol
• Grain vinegars
• White vinegar
• Vanilla extract and other flavorings (may contain alcohol)
• Amaranth
• Millet
• Buckwheat
• Quinoa
• Teff  

Wheat starch is used in the some countries gluten-free diet because of the belief that it contains only a trace or no gluten and that good baked products cannot be made without it. In a laboratory, wheat starch purity can be easily controlled, but in most plants this is not always the case. Wheat starch is not considered safe for celiacs in these countries: United States, Canada, Italy.

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• Anti-endomysial antibody (EMA)
• Anti-reticulin antibody (ARA)
• Anti-gliadin antibody (AGA)

Each of these three tests provide a certain degree of reliability for diagnosing celiac disease. Of these, endomysial antibody is the most specific test. The following table is taken from our studies (Lerner, Kumar, Iancu, Immunological diagnosis of childhood coeliac disease: comparison between antigliadin, antireticulin and antiendomysial antibodies).

The following definitions related to sensitivity, specificity, positive and negative predictive values may help:

Sensitivity is the probability of a positive test result in a patient with disease. Specificity is the probability of negative test result in a patient without disease. Positive predictive value is the probability of disease in a patient with positive test result. Negative predictive value is the probability of no disease in a patient with negative test result.

Karoly Horvath, M.D., Ph.D., Associate Professor of Pediatrics; Director, Peds GI & Nutrition Laboratory; University of Maryland at Baltimore: The summary below shows the results of the main serological tests based on several publications including 388 patients with celiac disease, and 771 healthy subjects.

SENSITIVITY- the proportion of subjects with the disease who have a positive test. It indicates how good a test is at identifying the diseased:

SPECIFICITY- the proportion of subjects without the disease who have a negative test. It indicates how good a test is at identifying the non-diseased:

POSITIVE PREDICTIVE VALUE- the probability that a person with positive results actually has the disease:

NEGATIVE PREDICTIVE VALUE- the probability that a person with negative results does not have the disease:

References:

McMillan SA, Haughton DJ, Biggart JD, Edgar JD, Porter KG, McNeill TA. Predictive value for coeliac disease of antibodies to gliadin, endomysium, and jejunum in patients attending for jejunal biopsy. Brit Med J 1991;303:1163-1165

Ferreira M, Lloyd Davies S, Butler M, Scott D, Clark M, Kumar P. Endomysial antibody: is it the best screening test for coeliac disease? Gut 1992;33:1633-1637.

Khoshoo V, Bhan MK, Puri S, Jain R, Jayashree S, Bhatnagar S, Kumar R, Stintzing G. Serum antigliadin antibody profile in childhood protracted diarrhea due to coeliac disease and other causes in a developing country. Scand J Gastroenterol 1989;24:1212-1216.

Chan KN, Phillips AD, Mirakian R, Walker-Smith JA. Endomysial antibody screening in children. J Pediatr Gastroenterol Nutr 1994;18:316-320.

Bode S, Weile B, Krasilnikoff PA, Gdmand-Hyer E. The diagnostic value of the gliadin antibody testing celiac disease in children: a prospective study. J Pediatr Gastroenterol Nutr 1993;17:260-264.

Calabuig M, Torregosa R, Polo P, Tom s C, Alvarez V, Garcia-Vila A, Brines J, Vilar P, Farr C, Varea V. Serological markers and celiac disease: a new diagnostic approach ? J Pediatr Gastroenterol Nutr 1990;10:435-442.

Karoly Horvath, M.D., Ph.D., Associate Professor of Pediatrics; Director, Peds GI & Nutrition Laboratory; University of Maryland at Baltimore: There are age dependent changes in several blood parameters during childhood. It is well known that immunoglobulin levels depend on the age of children. E.g. the IgA class immunoglobulins reach the adult level only by 16 years of age, and the blood level of IgA immunoglobulins is only 1/5th of adult value below two years of age. A large study from Europe (Brgin-Wollf et al. Arch Dis Child 1991;66:941-947) showed that the endomysium antibody test is less specific and sensitive in children below two years of age. They found that the sensitivity of the EmA test decreased from 98% to 88% in children younger than 2 years of age. It means that 12% of their patients with celiac disease, who were younger than two years of age, did not have an increase in their endomysium antibody levels.

Karoly Horvath, M.D., Ph.D., Associate Professor of Pediatrics; Director, Peds GI & Nutrition Laboratory; University of Maryland at Baltimore: If a patient has histologically (endoscopy) and serologically (antibody tests) proved celiac disease, and his/her symptoms disappeared on a gluten-free diet, a repeat biopsy is not necessary. The serological tests are useful tools for estimating the effectiveness of the diet after 3-6 months on a gluten-free diet. The disappearance of antibodies from the blood takes months, if there was not any accidental gluten challenge (dietary mistake).

Vijay Kumar, M.D., Research Associate Professor at the University of Buffalo and President and Director of IMMCO Diagnostics: I think your sons GI is doing the right thing. That is, if the EMA, ARA are normal (

Conscious sedation is performed with two different intravenous medications. One of them is a sedative medication (e.g. Versed), which causes amnesia in 80-90% of children, and even older children do not recall the procedure. The second medication is a pain-killer type medication (e.g. Fentanyl), which further reduces the discomfort associated with the procedure. In addition, the throat is sprayed with a local anesthetic in older children, which makes the throat numb and prevents retching at the introduction of the endoscope.

During general anesthesia the anesthesiologist uses sleep-gases (e.g. halothan) and intravenous medications and then places a tube into the trachea. Children are completely unconscious. This is a safer way to perform endoscopy, because the patients are fully relaxed and their airway is protected. However, the anesthesia itself has certain complications.

It is recommended to perform a full serological test-panel in patients with suspected celiac disease. These tests measure antibodies belonging to both the IgA and IgG classes of immunoglobulins. The incidence of selective IgA deficiency is much higher in celiac patients than in the general population. In patients with selective IgA deficiency only the IgG antigliadin antibody may be present, however, this antibody is less specific. It means that the IgG-type antigliadin antibody may be present in otherwise normal individuals.

If somebody had a positive endomysial antibody test at the time of diagnosis he/she may choose to use only this antibody test to monitor the effect of the diet. There are individual differences in the disappearance of serum antibodies.

Karoly Horvath, M.D., Ph.D., Associate Professor of Pediatrics; Director, Peds GI Nutrition Laboratory; University of Maryland at Baltimore: There are several advantages to use a laboratory experienced with the celiac serological tests:

• Technically, the test are more reliable, and the internal and external control of tests are better established than in laboratories where the celiac disease serology panel is only one of the routine tests
• More importantly, laboratories specialized in celiac serological testing have larger numbers of positive and negative samples to validate their tests and they are able to set up more accurately the negative, intermediate and pathologic values
• A laboratory specialized in these tests generally has a clinical background, and the physicians with experience in celiac disease may help in the interpretation of the results and they are happy to consult with other physicians and they can answer the questions of patients.