Celiac Disease and Gluten Sensitivity Detected Under the Microscope

INCREASED SPECIAL WHITE BLOOD CELLS IN INTESTINE IS THE EARLIES SIGN OF GLUTEN INTOLERANCE AND CELIAC DISEASE

Specialized white blood cells known as lymphocytes are present in the tips of the villi of small intestine. They are believed to be important in surveying the digestive tract for potential invaders or attacks from viruses, bacteria and parasites. In the context of leaky gut that can occur from eating gluten containing grains and flour, these lymphocytes can increase in numbers at the tips of the intestinal villi. This change is critical in the development of celiac disease (CD).

INCREASES IN INTESTINAL LYMPHOCYTES CAN BE SEEN UNDER THE MICROSCOPE BEFORE DAMAGE OF THE INTESTINE LINING IS SEEN

Though not specific for CD, increased lymphocytes in the tips of the villi, also known as increased intraepithelial lymphocytosis, is accepted as the earliest sign of gluten intolerance in the gut. This increase when significant is obvious to most pathologists reviewing biopsy slides from tissue obtained from the intestine during a scope examination. However, this may not be obvious without an objective count of the number lymphocytes in the tips of the intestinal villi.

HOW DO THE PATHOLOGISTS COUNT THE NUMBER OF LYMPHOCYTES IN THE INTESTINAL LINING AND WHAT IS NORMAL?

Most pathologists either report the number of IEL's per 20 intestinal lining cells (enterocytes) or per 100 enterocytes. Generally there are only 1-4 lymphocytes in the tips of each villous where there are typically 20 intestinal cells. When the pathologist or a computerized counting microscope reports or counts the lymphocytes per 100 intestinal cells there are usually no more than 12-15 per 100 intestinal lining cells. In the past, 40 lymphocytes per 100 intestinal cells (or about 8 per villous tip) was considered the cut off for abnormal. More recently that number has been lowered to 30 lymphocytes per 100 intestinal or epithelial cells (about 6 per villous tip). There are some researchers who believe the number should be lowered to 25 per 100 (or about 5 per villous tip).

WHAT ARE CAUSES OF INCREASED WHITE BLOOD CELLS OR LYMPHOCYTES IN THE INTESTINE?

Celiac disease is the most common but infection from the ulcer causing bacterium Helicobacter pylori or the parasite giardia can be a cause as well as recent viral infection. Cow's milk protein sensitivity and allergy is also a cause. Though not well established, it is believed that the number of lymphocytes in conditions other than Celiac disease or gluten intolerance may not be as high.

Inflammatory conditions in the esophagus, stomach, distal small bowel or colon may be associated with increased IEL's in those areas but the number has not been well studied. There is a concern that some pathologists may falsely attribute increased duodenal lymphocytes to associated inflammation going on in either the esophagus or stomach. Increased lympnocytes have been noted in the gut above the duodenum (esophagus and stomach) and below the jejunum (ileum and colon) in both celiac and microscopic or collagenous colitis caused by gluten sensitivity.

WHAT IS CELIAC DISEASE?

Celiac disease is an autoimmune disease of gluten intolerance or sensitivity not a food allergy though many people mistakenly refer to it as gluten allergy or wheat allergy. Previously thought to be rare it is now known to be very common, affecting 1/100 worldwide.

Celiac Sprue, as CD is also commonly known, is definitively diagnosed by the combination positive results for specific blood antibodies for CD, either endomysial (EMA) or tissue transglutaminase (tTG); a characteristic small intestine biopsy; and response to a gluten-free diet (GFD). Classically, flattening of the intestinal villi, known as villous atrophy, has been the gold standard for diagnosis. Positive EMA or tTG tests without villous atrophy on biopsy but increased IEL's is accepted as diagnostic in the context of response to GFD, especially when an individual is positive for one of the two predisposing genes, DQ2 or DQ8.

WHAT DID THIS RECENT STUDY FIND REGARDING THE NUMBERS OF LYMPHOCYTES IN THE DIGESTIVE LINING?

A recent study of biopsies of the esophagus, stomach, and duodenum of 46 people without Celiac disease reached several conclusions. Though there may be a slight increase in lymphocytes in esophagitis and gastritis, the difference in lymphocyte numbers is not significantly different in normal biopsies of the esophagus and stomach. Though general ranges of duodenal lymphocytes found in active esophagitis (2-13, average 8.8), active gastritis with Helicobacter pylori infection (2-13, average 7.2) and chronic gastritis without H. pylori infection (4-20, average 10.2) was very similar to those with negative esophagus, stomach and duodenal biopsies (2-18, average 6.7) the average number of lymphocytes was slightly higher, though not statistically significant.

WHAT MIGHT THIS TELL US ABOUT LYMPHOCYTE NUMBERS IN THE INTESTINE?

In my opinion, I believe this study showed that the numbers of lymphocytes in people with normal biopsies, esophagitis and gastritis were significantly lower than those reported in people with Celiac disease (>30/100 ) and early gluten injury (20-25/100 enterocytes) but not meeting diagnostic criteria for Celiac disease. I believe this study is helpful because it argues against attributing more than 20-25 lymphocytes/ 100 enterocytes to other inflammatory processes in the esophagus or stomach. It also supports the findings of other studies that have found that >20-25 /100 as an early sign of gluten sensitivity.

WHAT ABOUT LYMPHOCYTE COUNTS LESS THAN 30 BUT 25 OR MORE?

In the context of elevated gliadin antibody levels I believe that intestinal lymphocyte counts in the villi of 25 or more likely indicates gluten sensitivity though it does not necessarliy mean Celiac disease. Strict criteria for diagnosing of this disease require a positive specific blood test such as endomysial antibody or tissue transglutaminase antibody and >30 IEL's/100 enterocytes and evidence of villous atrophy on small intestinal biopsy.

WHAT SHOULD I TAKE FROM THIS?

If you have had an intestinal biopsy but were told you did not have signs of Celiac disease, I recommend you consider asking that biopsy be reviewed by another pathologist who has experience in Celiac disease and you ask them to provide you with the number of lymphocytes in the villi. If they provided the number and you find there were 30 or more then that is clearly abnormal and can be diagnostic of Celiac disease if you have a positive specific blood test such as the endomysial or tissue transglutaminase antibodies, especially if you carry either the DQ2 and/or the DQ8 genetics. If you have less than 30 lymphocytes per 100 enterocytes but 20 or more and have a gliadin antibody elevation I would recommend you get HLA DQ genetic testing and try a gluten free diet.