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New Developments in CD Research and Rectal Challenge, Dr. Michael
----------------------------------------------------  Marsh,
University of Manchester Medical School, England

Dr. Marsh believes it is probable that the avenins in oats are not
toxic to celiacs.

The regulation of the immune systems is brought about by genes.  In a
celiac the response is not controlled; the immune system fails the
"self/non-self" test, causing an inappropriate response.

The antigen is in highest concentration in the jejunum, therefore the
highest number of T-cells can be found there.  However, even down in
the rectum some of the T-cells exist.  Therefore, a rectal challenge
with gluten will result in inflammation in a celiac.

Dr. Marsh described the rectal gluten challenge as a diagnostic and
management tool.  The premise of the test is that a gluten challenge
can be conducted anywhere in the intestinal tract and show a reaction.
The T lymphocytes are the agents of damage, and in celiacs produce an
uncontrolled response.  With a biopsy after 4 hours, computer
scanning, and mathematical analysis software, it is possible to
separate celiacs from controls with 100% certainty.  [Editor's note:
There doesn't appear to be a published dispute with Dr. Marsh's
findings, but there also does not appear to be a published duplication
of his results from other sources.]

How do we measure this response?  There are three areas to consider:
the surface epithelia, the crypt epithelia, and the lamina propria in
between.  A 100 x 100 micron area is used as the standard to compare
against.

Here is a comparison of the number of lymphocytes found in the 100x100
micron area:
                      Controls   Untreated CD
   surface epithelium    2.6          0.6
   crypt epithelium      0.6          1.9
   lamina propria        1.4          2.8

Loft reported the results of a study in *Gastroenterology* 1989.
There were 10 subjects and 6 controls.  Gluten was introduced to the
rectal tissue.  A biopsy afterwards showed an inflammatory response in
celiacs, but not in the controls.  In only 6-8 hours there was a
noticeable increase in crypt epithelial lymphocytes in celiacs.

Ensari (Turkey) repeated Loft's work, with additions.  There were 31
celiacs and 34 controls.  For this study, an untreated celiac was
defined as having "flat mucosa".  Signam brand gluten was used as the
antigen.  Biopsies were done at 0, 2, and 4 hours.  At each interval
they looked at gamma, delta, and various other T-cells, along with
routine blood tests, fecal fat, xylose excretion, and jejunal biopsy.

After 2 hours there were changes that tended to separate celiacs from
non-celiacs.  The sensitivity was about 70%, specificity about 80%.

After 4 hours the changes were more marked.  Celiacs and non-celiacs
were clearly separated.  Sensitivity and specificity were both 100%.
This looked "embarassingly good"; they didn't "cook" the figures.

Regression analysis compared with all the other potential diagnostic
tests shows only the jejunal biopsy matches the 4-hour rectal gluten
biopsy in specificity and sensitivity.

So why use the rectal challenge?

  * It is relatively easy.
  * It uses a well-documented protocol.
  * It works for any age group.
  * It finds latent/refractory sprues.
  * It is a dynamic test.  (All other tests are passive, 'after-the
       fact' tests.)

Note:  The rectal challenge does NOT work in patients that are on a GF
diet, so it is no different from the jejunal biopsy or the blood tests
in this respect.  It may still be useful though if the patient has
been on a GF diet for 6 months or less.

Dr. Marsh then answered some questions from the floor.


Q: What diseases did the controls have in your study?

A: Diarrhea, iron deficiency, bone disease, etc.; all were coming to
   the clinic anyway.


Q: Did the technician know which samples were from celiacs and which
   were controls prior to counting lymphocytes?

A: No, she had no idea.


Q: How can people in Canada get access to this test?

A: Right now you probably can't.  It is not in wide use in the USA or
   Canada.  Dr. Murray responds:  It is fairly new; it is not
   standardized between labs.  Also people in general are opposed to
   having items inserted in their rectums.  (Not all audience members
   agreed.)  Also the studies need to be repeated and verified
   elsewhere.