Ataxia is a neurological condition that affects the coordination of muscle movements.  Individuals with ataxia may have difficulty with balance when standing or walking.  There are many different causes of ataxia, ranging from inherited diseases to certain kinds of strokes.  But ataxia is connected to celiac disease in two ways:

• Some individuals with ataxia have been found to have celiac disease, and this association has been termed “gluten ataxia.”

• A deficiency in vitamin B12, which can occur in individuals with uncontrolled celiac disease, can cause ataxia.


Antibodies are proteins synthesized and secreted by white blood cells with the primary function of recognizing and destroying bacteria and viruses.  Antibodies are essential for health, and the development of antibodies begins in infancy and continues throughout life.  But some antibodies recognize and attack the host’s own body instead of attacking germs.  These are called autoantibodies.  Certain diseases such as autoimmune thyroid disease and lupus are triggered or worsened by these autoantibodies.

What does this have to do with celiac disease?  The blood tests used to diagnosis and follow celiac disease, anti-tissue transglutaminase and anti-endomysial antibodies, are actually autoantibodies against a set of enzymes and tissue that exist throughout the body.  At this point it is uncertain whether these autoantibodies are a significant cause of the many associated illnesses that coexist with celiac disease, or whether these autoantibodies are a byproduct of intestinal damage, but the existence of these autoantibodies supports our growing understanding of celiac disease as an autoimmune disease.

Autoimmune disease

An autoimmune disease is condition in which illness is caused by one’s own immune system.  Instead of targeting bacteria and viruses, the immune system in autoimmune disease mistakenly recognizes the host’s own organs and tissue as foreign.  Examples of autoimmune diseases include lupus, rheumatoid arthritis, multiple sclerosis, Type 1 diabetes, autoimmune thyroid disease, primary biliary cirrhosis, Sjogren’s syndrome, and psoriasis.  In nearly every case, the underlying trigger of the autoimmune disease is unknown.  But celiac disease is an autoimmune disease in which the trigger is known: eating gluten-containing food.  For this reason, celiac disease is the subject of intense interest among research scientists who specialize in understanding the immune system in health and disease.

Vitamin B12

This nutrient is involved in cell metabolism and is essential to normal health.  Deficiency in vitamin B12 can cause a variety of symptoms: neuropathy (numbness and tingling), ataxia (difficulty with balance), psychiatric disturbance ranging from mild depressive symptoms to severe loss of cognitive function, and low energy level.  Vitamin B12 is obtained from the diet and is found in meat, poultry including eggs, and dairy food.

Patients with celiac disease can sometimes develop vitamin B12 deficiency.  The absorption and processing of vitamin B12 is complex, and celiac disease can affect several steps in this process.

• Adequate acid levels are needed in the stomach for proper digestion of vitamin B12, and some patients with celiac disease have a condition of low acidity called atrophic gastritis.

• Absorption of vitamin B12 in the small intestine depends on adequate pancreatic function, and some individuals with celiac disease have impaired pancreatic function.

• Vitamin B12 is absorbed in the ileum, the last part of the small intestine.  While this portion of the intestine is usually not affected in celiac disease, in certain cases this can occur and then interfere with vitamin B12 absorption.

• Patients with celiac disease are at increased risk of small intestinal bacterial overgrowth, a condition in which the levels of bacteria in the bowel are higher than normal.  In this condition, the bacteria can “compete” with the patient for vitamin B12, resulting in lower levels of vitamin B12 in the host.

Vitamin B12 deficiency is diagnosed via blood test, and can be treated in a variety of ways.  Vitamin B12 supplements can be taken in pill form, in a tablet under the tongue, as a nasal spray, or via injection.  The best route to replenish vitamin B12 depends on the specific cause of the deficiency, and on how low the B12 level is.


As a generic term, a biopsy refers to taking a sample of living specimen for examination under the microscope in order to aid in making a diagnosis.  In celiac disease, the biopsy of the small intestine during upper endoscopy is crucial for establishing the diagnosis.  The small intestine in celiac disease has a characteristic appearance that can vary in severity.  It can range from a mild increase in the number of immune cells at the surface of the intestine all the way to a severe flattening of the normally-fingerlike projections of the intestinal wall.

Interpreting the biopsy to establish (or “rule out”) celiac disease is not always straightforward.  The abnormalities in the intestine can be patchy, i.e. they can be present in one area of the intestine but not in others.  For this reason, taking an adequate number of biopsies is essential.  Especially in the case of subtle abnormalities, we recommend that biopsies be interpreted by a pathologist with expertise in celiac disease.

Capsule Endoscopy

Capsule endoscopy refers to a technique of examining the bowel in which a pill with a tiny camera is swallowed and takes thousands of pictures that are then transmitted wirelessly to a computer.  This technique is most commonly used to inspect the small intestine in the regions that are difficult to reach using an endoscope.  This technology has existed for more than 10 years and is done routinely on an outpatient basis.

Some individuals with celiac disease may benefit from capsule endoscopy.  Situations that may warrant a capsule endoscopy include a patient who is poorly responsive to the gluten free diet, or who has persistent anemia despite a normal upper endoscopy and colonoscopy.  Some individuals whose celiac disease status is uncertain may benefit from capsule endoscopy so as to evaluate for abnormalities throughout the small bowel, and to search for an alternative diagnosis.

Celiac Disease

Celiac disease is an autoimmune disease that is triggered by eating gluten, which is present in wheat, rye, and barley.  This disease has a genetic basis, in that there are several common gene variants that are necessary for the development of celiac disease.  But the fact that celiac disease has been increasing in the past 50 years (based on blood tests of frozen samples from the 1950’s) indicates that there is an environmental aspect to the development of celiac disease that we do not yet understand; our genes have not changed considerably in the past 50 years, so there must be something in the environment (possibly including our exposure—or lack of exposure—to germs, or the preparation and processing of dietary gluten) that has changed to account for this rise.  Celiac disease is now present in approximately 1% of the population of the United States.

The route to a diagnosis of celiac disease begins with the suspicion of this disease; as there is a lack of awareness among many physicians regarding how common celiac disease is, the process of the diagnosis of celiac disease is often initiated at the suggestion of the patient.  The next step is usually a blood test, which is positive in most individuals with celiac disease.  The diagnosis is then confirmed via biopsy of the small intestine, which shows characteristic changes that are compatible with celiac disease.

Treatment of celiac disease is with a gluten-free diet, which at this point is a life-long commitment.  As gluten can be present in many guises, we advise that all patients with celiac disease meet with an expert dietician for education and guidance regarding this diet.  Patients with celiac disease should be followed regularly for “flares” of disease activity, which may occur even in the absence of symptoms, but which can be identified via blood test or biopsy.  Patients should also be checked regularly for various nutritional deficiencies, which can occur either as a result of ongoing celiac disease activity, or as a result of the gluten-free diet which can be lacking in certain vitamins and minerals.


This refers to a procedure in which a tube with a fiberoptic camera is inserted into the gastrointestinal tract.  An upper endoscopy involves insertion of this tube into the mouth and through the esophagus, stomach, and the duodenum (the first part of the small intestine).  This procedure is performed on an outpatient basis and takes approximately 15-25 minutes.  While not a painful procedure, patients are usually given intravenous sedation to maintain comfort.  A diagnosis of celiac disease requires a biopsy of the small intestine, and this occurs during the endoscopy.

Folate (Folic acid)

Folate is a nutrient that is essential to the function of cells.  It is especially active in areas of cell division/replication, such as the formation of red blood cells and the development of a fetus.  Low levels of folate can cause anemia and birth defects.  Folate is present in green leafy vegetables and in fortified grain products.

Individuals with celiac disease are at risk of developing low levels of folate for two reasons.

• Folate is absorbed in the part of the intestine (the duodenum) that is most commonly affected in celiac disease.

• Many gluten-free grains are not fortified with folate the way that wheat is.

For these reasons, patients with celiac disease should have their folate levels periodically checked, and supplemented when necessary.


Gluten refers to a type of protein that is found in wheat, rye, and barley.  Gliadin is a component of gluten that generates an abnormal immune response leading to damage of the intestinal wall in celiac disease.  One of the newer antibody tests for celiac disease, the Deamidated Gliadin Peptide (DGP) tests for the presence in the blood of antibodies against a specific state of gliadin that is particularly “primed” for the immune system in celiac disease.

Not all grains contain gluten, and patients with celiac disease should meet with a nutritionist so as to become more familiar with the gluten-free grains.  Such “safe” grains include quinoia, buckwheat, and teff.

Gluten Sensitivity

Gluten sensitivity is a relatively new concept referring to the condition of symptoms—really, any of the diverse symptoms associated with celiac disease—that improve on a gluten free diet, but with a biopsy that is normal.  Some patients with gluten sensitivity may have blood tests consistent with celiac disease, but many do not.

Our understanding of gluten sensitivity remains limited, and this is a ripe area for research.  Do some of these patients probably have celiac disease but had a misinterpreted biopsy or had abnormalities in other parts of the bowel that were not biopsied?  Certainly.  But then there are other patients who clearly do not meet the definition of celiac disease and yet they feel better on the gluten free diet.  We do not know the natural history of this condition.  For example, in celiac disease, you need to be on a gluten free diet permanently—you can’t “grow out of it.”  We don’t know if that’s the case in gluten sensitivity.  There is a mildly increased risk of certain cancers celiac disease that seems to be reduced when on a gluten free diet—we don’t know about the risk in gluten sensitive individuals.

One thing is certain—a diagnosis of gluten sensitivity can’t be appropriately made if you haven’t been fully assessed for celiac disease.  This requires the blood test and a biopsy.  Without these tests, it’s impossible to know if someone has celiac disease or has this newly recognized diagnosis of gluten sensitivity.

HLA (Human Leukocyte Antigen)

Everyone has a set of protein complexes used by the immune system to facilitate the recognition of bacteria, viruses, and other “invaders.”  These proteins are called the Human Leukocyte Antigen (HLA), and they come in a number of different types, akin to a blood type.  A particular set of HLA types, known as DQ2 and DQ8, are present in the vast majority (some say 100%) of individuals with celiac disease.  Getting “the gene test” for celiac disease is checking for whether your HLA type is DQ2/DQ8 or not.

These HLA types are quite common in the general population; approximately 30-40% of individuals in the United States carry this type.  So a positive test does not indicate celiac disease, but it indicates that celiac disease is possible.  In fact, this gene test is most useful when the result is negative for DQ2/DQ8, as such a result means that celiac disease is not present, nor is the individual at risk for developing celiac disease in the future.  This gene test can be performed using blood or via a cheek swab.


This refers to damage to the nerves.  When this affects the peripheral nerves that detect light touch on the extremities, this entity is called peripheral neuropathy, a common condition.  There are many causes of peripheral neuropathy, including diabetes, certain infections and medicines, but in a sizeable proportion of individuals the cause is not known.  Researchers at the Celiac Disease Center at Columbia University have found that celiac disease is present in some patients with peripheral neuropathy without clear cause, and that the neuropathy sometimes improves dramatically after starting a gluten-free diet.

The relationship between celiac disease and peripheral neuropathy is not completely understood, and is the subject of active research efforts.  The neuropathy may be a reflection of the autoimmune nature of celiac disease.  Alternatively, neuropathy may occur in celiac disease due to certain nutrient deficiencies.


The prevalence of a disease refers to how common a disease is in a population.  Celiac disease was previously thought to be rare in the United States; it was thought to have a low prevalence.  In fact, we now know that celiac disease is common in this country.  The prevalence of celiac disease is approximately 1%, i.e. 1 in 100 individuals in the United States has celiac disease (though most with the disease remain undiagnosed at this time).


Osteoporosis refers to the condition of decreased bone mineral density.  Bone is composed of a matrix of mineralized tissue that can vary in density, or the amount of matter packed into a given area.  The density of bone can be measured using densitometry, a form of X-ray.  Bone density below a critical threshold is termed osteoporosis.  The significance of this diagnosis is that individuals with osteoporosis are at increased risk of fracture of the hip, wrist, spinal column, and other bones.  Adequate calcium and vitamin D intake can prevent or delay osteoporosis in some individuals, but once osteoporosis is found, other medications are often required to increase bone density.

People with celiac disease have increased rates of osteoporosis, likely related to inadequate absorption of calcium and vitamin D in the intestine.  An autoimmune component to osteoporosis may also be at play in celiac disease.  Because of this association, individuals with celiac disease should have their vitamin D calcium levels monitored, and should have their bone density measured.

Tissue Transglutaminase (TTG)

Tissue transglutaminase is an enzyme, a type of protein that facilitates biological processes throughout the body.  Tissue transglutaminase functions in many tissues, but in patients with celiac disease, this enzyme interacts with gliadin (a component of gluten) in the intestinal wall to make gliadin more susceptible to attack by the immune system.  Tissue transglutaminase therefore facilitates the process of intestinal damage in celiac disease.  As additional evidence of the important role that tissue transglutaminase plays, antibodies to this enzyme are present in individuals with celiac disease.  In fact, anti-TTG is a common screening test for celiac disease.


The primary function of the small intestine is to absorb nutrients.  This is accomplished by means of a large surface area.  The surface of the healthy small intestine is actually a series of long finger-like projections called villi.  Although the small intestine is nearly 20 feet in length, the actual surface area of the small intestine is much larger due to these villi, approximating the size of a tennis court!  In celiac disease, the architecture of the villi is distorted as a result of the interaction in the intestinal wall between the immune cells and gluten.  This phenomenon is known as villous atrophy.  This can be seen under the microscope and is one of the hallmark findings of biopsy-proven celiac disease.  In the most severe form, villous atrophy can be so extensive that the finger-like projections cannot be seen at all; as a result, the intestinal wall appears flat.  As a result of this markedly reduced surface area, absorption of nutrients is repaired.

Villous atrophy generally recovers once gluten is eliminated from the diet, but the recovery can sometimes be a slow process, even lasting years.  Given this time lag between eliminating gluten and full normalization of the villi, a biopsy is sometimes helpful in the setting of an individual whose celiac disease status is uncertain but who is adhering to a gluten-free diet