Celiac and Non-Celiac Gluten Sensitivity: Intraepithelial lymphocyte numbers and blood tests

My abstract “Clinical Characteristics and Prevalence of Celiac Disease and Non-Celiac Gluten Sensitivity Presenting to a Community Based Private Gastroenterology Clinic” was published in the in the supplement of the September 2007 issue of the American Journal of Gastroenterology. Sadly, mine is the only abstract addressing non-Celiac gluten sensitivity for the annual meeting of the American College of Gastroenterology in 2007. The overall number of presentations on Celiac disease remains few at our annual meeting.

I reviewed my data for two years. I chose this limited period because it has only during that period that I have been compulsively following a very extensive work up for Celiac disease that includes determination of HLQ DQ patterns when covered by insurance or the patient voluntarily pays for the testing. During this timeframe I also requested that the pathologists report the exact number of lymphocytes in the small intestine biopsy.

My data revealed that although women outnumbered men almost 3:1 in all patients that presented to me for evaluation, this ratio narrowed to 1.4:1 in confirmed Celiac disease, which was 12.5% of all patients. My experience is consistent with other reports of more than 10% of patients with symptoms who present to a gastroenterologist that are screened adequately have Celiac disease. Sadly, this rate of high prevalence of Celiac disease in patients with GI symptoms is unknown to most doctors including many gastroenterologists. The prevalence of confirmed Celiac disease in people with GI symptoms exceeds 10% compared to the asymptomatic blood donor data of approximately 1%, equivalent to the population randomly selected from a crowd at a mall or at a sporting event.

HLA DQ genetics were obtained in almost 70% of my patients. DQ2 was present in 55% and DQ8 in 22%. Everyone with a positive endomysial antibody and/or tissue transglutaminase antibody was positive for either DQ2 and/or DQ8. This is consistent with the prevailing belief that DQ2 or DQ8 must be present to have what is now considered strict criteria for the definitive diagnosis of Celiac disease, that is, a positive EMA and/or TTG along with a characteristic abnormal small bowel biopsy. However, many people with early Celiac disease and all people with non-Celiac gluten sensitivity will have negative EMA and TTG though they frequently have elevated gliadin antibodies in the blood or stool.

IgA deficiency, a known cause of false negative EMA and TTG blood tests, was present in 13% of those with Celiac disease compared with only 4% of people overall. This is consistent with reports that IgA deficiency is present in more than 10%, though some studies have found much lower rates. My findings would support the recommendation of most Celiac experts that IgA levels be determined at time of Celiac disease blood tests to avoid missing the diagnosis because of IgA deficiency.

Another interesting finding that those considered having non-Celiac gluten sensitivity based on symptoms, elevated gliadin antibodies in blood or stool, and response to gluten free diet; had elevated intraepithelial lymphocyte counts in the small intestine. Though these were on average not as high as those with Celiac disease well above the normal of <15/100 and approached the numbers that are considered diagnostic and borderline, 30/100 and 25/100 respectively. In CD the IEL counts averaged 47/100 enterocytes whereas in NCGS they averaged 23/100.

My conclusions, that were recognized significant by the selection of the abstract for a poster presentation, are as follows. I concluded that estimated prevalence of Celiac disease of 1% significantly underestimates that of patients presenting to a gastroenterologist. Total IgA levels should be measured in all patients being screened for Celiac disease. Antigliadin antibodies, though not specific for Celiac disease, may identify patients with elevated IEL counts and villous blunting on small bowel biopsy who will respond favorably to a gluten free diet, though may or may not have early Celiac disease. These non-Celiac gluten sensitive individuals exist though they are largely hidden from the Celiac disease radar because of a bias to focus on traditional or strict criteria for diagnosis Celiac disease before recommending a gluten free diet.

Since almost 13% of symptomatic individuals have Celiac disease (and many more have NCGS) and IgA deficiency occurs commonly in CD, I recommend that all symptomatic patients be screened thoroughly. In my practice this includes a complete Celiac disease blood panel, including total serum IgA levels and gliadin antibodies, and a small bowel biopsy with determination of numbers of intraepithelial lymphocytes prior to trial of a gluten free diet whenever possible.

If EMA or TTG are positive it is almost certain that DQ2 or DQ8 is present though confirming the number of copies of one of the other can be helpful for genetic counseling and deciding how to approach screening other family members. If these blood tests are negative, it is not known if one is genetically at risk for Celiac disease without specifically testing for DQ2 or DQ8, so whenever possible I request these tests on anyone I suspect of having Celiac disease or non-Celiac gluten sensitivity. A recent article and accompanying editorial reviewed the pros and cons of genetic testing in context of screening by blood tests for Celiac disease. Though the reviews do have some very helpful information it must kept in mind that the absence of DQ2 and DQ8 does not exclude NCGS.

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References:

Lewey, SM. “ Clinical characteristics and prevalence of celiac disease and non-celiac gluten sensitivity presenting in a community based private gastroenterology clinic. Abstract #255. Am J Gastro. 102(S2), 2007.

Hadithi, M. “Accuracy of serologic tests and HLA-DQ typing for diagnosing Celiac disease” Ann Intern Med. 2007;147:294-302.

Murray, JA and Rashtak, S. “Tailored testing for Celiac disease” Ann Intern Med. 2007;147:339-341.