Celiac Disease Versus Gluten Sensitivity: New Role for Genetic Testing and Fecal Antibody Testing?

Celiac Disease Versus Gluten Sensitivity: New Role for Genetic Testing and Fecal Antibody Testing?

By Dr. Scot Lewey

Tip! One natural remedy for Celiac is Cardamon, which is found in India. It has been used successful in treating Celiac disease in children.

Celiac disease (CD) has a prevalence of 1/100. Between 90-99% of Celiacs are HLA
DQ2 and/or DQ8 positive. Every individual has two DQ serotypes. Because the
molecular HLA nomenclature can be confusing DQ serotyping is a method for
simplifying the results. There are four major types and 5 subtypes: HLA DQ1, DQ2,
DQ3 and DQ4; DQ1 has two subtypes; DQ5 and DQ6 whereas DQ3 has three
subtypes; DQ7, DQ8 and DQ9. Each individual has two copies of HLA DQ. One DQ
type is inherited from each parent.

Though 35-45% of individuals of Northern European ancestry are DQ2 &/or DQ8
positive only 1% have classic CD as defined by abnormal blood tests and small
intestine biopsies. Several autoimmune conditions also occur more frequently in
DQ2 and DQ8 positive individuals.

There is accumulating scientific evidence that many individuals are gluten sensitive
and respond to a gluten free diet though they have normal blood tests and/or
normal intestinal biopsies (fail to meet strict criteria for CD). This is more commonly
being referred to as non-Celiac gluten sensitivity (NCGS). Many individuals who
have NCGS are relatives of confirmed Celiacs and were previously referred to as
latent Celiacs. Electron microscopy and immunohistochemistry studies of
individuals with normal biopsies but suspected of or at risk (1st degree relatives of
Celiacs) have revealed ultrastructural abnormalities of the intestine and those who
chose gluten free diet usually responded and many who did not ultimately
developed abnormal biopsies on long term follow-up. Seronegative Celiac has also
been recognized, that is blood tests are negative, but the biopsy reveals classic
abnormalities of Celiac and the individual responds to gluten free diet.

Fecal antibody testing for gliadin (AG) and tissue transglutaminase (tTG) by
Enterolab in Dallas has revealed elevations in 100% of Celiacs tested and up to 60%
of symptomatic individuals without Celiac disease (NCGS) even if not DQ2 or DQ8
positive. (Fine, K unpublished data, www.enterolab.com). The only DQ pattern he
found not associated with gluten sensitivity is DQ4/DQ4, a pattern typically found in
non-Caucasians who are known to have a low prevalence of Celiac disease.

Testing for DQ2/DQ8 has been suggested as a way to exclude CD. That is, if you are
negative for DQ2 and DQ8, then you are very unlikely to have CD. However, well
documented cases of CD and Dermatitis Herpetiformis (DH) have been confirmed in
DQ2 and DQ8 negative individuals. Moreover, we now have the clinical experience
that other DQ patterns predispose to gluten sensitivity because these individuals
frequently have elevated fecal antibodies to AG or tTG and respond to gluten free
diet.

Why some people develop Celiac Disease or become sensitive gluten is not well
understood. Risk factors include onset of puberty, pregnancy, stress, trauma or
injury, surgery, viral or bacterial infections including those of the gut, medication
induced gut injury or toxicity (e.g. NSAIDs), immune suppression or autoimmune
diseases, and antibiotic use resulting in altered gut flora (dysbiosis). The severity of
the sensitivity is related to the DQ type, pre-existing intestinal injury, degree of
exposure to gluten (how frequent and large a gluten load an individual is exposed
to), and immune status. Once initiated, gluten sensitivity tends to lifelong. True CD
requires lifelong complete gluten avoidance to prevent serious complications,
cancers, and early death.

Tip! I recommend you help your doctor if you believe you may have Celiac disease or gluten sensitivity by 1) Writing down all your symptoms and your understanding of how they may be due to gluten sensitivity 2) Sharing your family history, including your ancestry and any genetic tests done 3) Being familiar with the diagnostic tests for Celiac disease and gluten sensitivity and their limitations 4) Politely ask your doctor to test you for Celiac disease pointing out why you believe it may be a cause of your symptoms 5) Being willing to undergo adequate and appropriate evaluation and 6) Being prepared to obtain a second opinion if necessary. Being educated and prepared will help your doctor help you.

Serotypes can be determined from blood or buccal mucosal cells obtained by oral
swab from several commercial labsl including Prometheus, Labcorp, Quest, The
Laboratories at Bonfils, and Enterolabs. Fecal IgA anti-gliadin and IgA tissue
transglutaminase antibody testing is only available in the U.S. commerically through
Enterolabs. The fecal AG and tTG testing may be helpful in those with normal blood
tests for Celiac and/or a normal small bowel biopsy but suspected of being gluten
sensitive. Though the fecal antibody results are not widely accepted by many "Celiac
experts" numerous testimonials of individuals testing positive only on fecal tests
who have responded to gluten free diet can be found in support groups, web
postings, personal communication from Dr. Fine and this physician's clinical
experience.

Bibliography

Abrams et.al. Seronegative celiac disease:increased prevalence with lesser degrees
of villous atrophy. Dig Dis Sci 2004;49:546-550.

Alaedini A. and Green P.H.R. Narrative Review: Celiac Disease: Understanding a
Complex Autoimmune Disorder. Ann Intern Med. 2005;142:289-298.

Arranz et. al. Jejunal fluid antibodies and mucosal gamma/delta IEL in latent and
potential coeliac disease. Adv Exp Med Biol. 1995; 371B:1345-1348.

Dewar D. and Ciclitira P. Clinical Features and Diagnosis of Celiac Disease.
Gastroenterology 2005;128:S19

Kappler et.al. Detection of secretory IgA antibodies against gliadin and human
tissue transglutaminase in stool to screen for coeliac disease in children:validation
study. BMJ 2006; 332:213-214

Tip! Gallbladder disease should be considered in Celiac disease patients despite normal ultrasound and HIDA tests, especially if a 'supranormal' ejection fraction is noted and pain reproduced with CCK. Patients with abnormal high gallbladder ejection fractions should be considered as possible undiagnosed Celiacs and should undergo blood tests for Celiac disease and consideration of upper endoscopy with small bowel biopsy.

Kaukinen et.al. HLA-DQ Typing in the Diagnosis of Celiac Disease. Am J
Gastroenterol. 2002;97(3):695-699.

Fine KD and Rostami K. Don't throw the baby out with the bath water. BMJ February
13, 2006 rapid response editorial

Fine K. Early diagnosis of gluten sensitivity before the villi are gone. Transcript of
presentation to Greater Louisville Celiac Support Group, June 2003.
www.enterolab.com/essay/

Picarelli et.al. Antiendomysial antibody detection in fecal supernatants:in vivo proof
that small bowel mucosa is the site of antiendomysial antibody production. Am J
Gastroenterol. 2002 Jan;97(1):95-98

Sbartati A. et.al. Gluten sensitivity and "normal" histology: is the intestinal mucosa
really normal? Dig Liver Dis 2003;35:768-773.

Sollid L. and Lie B. Celiac Disease Genetics:Current Concepts and Practical
Applications. Clinical Gastroenterology and Hepatology 2005;3:843-851.

WGO-OMGE Practice Guideline Celiac Disease. World Gastroenterology News.
2005;10(2):supplement 1-8.

Dr. Scot Lewey is a physician who is trained and board certified in the specialty of
gastroenterology (diseases of the digestive tract) and has a growing practice focused in
the area of food intolerances, especially gluten and cow's milk protein. He is a
published researcher and author and founder of an educational website
http://www.thefooddoc.com dedicated to helping people with food intolerances.