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From:
Hill, Deirdre (NCI) <[log in to unmask]>
Date:
Mon, 1 May 2000 17:13:45 -0400
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<<Disclaimer: Verify this information before applying it to your situation.>>

  Hi List Members;

   Thanks to everyone who expressed interest or had questions regarding
the new finding of increased levels of a protein called "zonulin" in
those with celiac disease.  Several interesting questions were raised,
which I will try to summarize.  (I've also included the little that I
could find that addresses these questions, but want to state clearly
that this is not my field).

1. Can celiac disease possibly be diagnosed by testing for zonulin?
2. Can zonulin be blocked, and will that prevent/treat celiac disease?
3. Where was the original research published?

   In the interim, someone has posted the answer to question #3 (thank
you!)- the reference is:  Lancet 2000; vol.  355:  pgs.  1518 - 1519.
The Lancet is a well-known medical journal that is often available in
local libraries, and if not, in the libraries of community hospitals or
colleges.  I can't post the full article here because of copyright
restrictions.  But here is an excerpt that partially addresses question
#1:

"We used a ZOT-based ELISA to detect antibodies to zonulin in the serum
samples of patients with coeliac disease and controls.  Anti-zonulin
IgG was not higher in patients with coeliac disease than controls.  By
contrast, anti-zonulin IgA was raised in the serum samples of 25 of 117
(21%) patients with coeliac disease during the acute phase of the
disease but in none of the 30 patients in remission (p<0o0001).  Only
nine of 163 (6%) healthy controls had a minimally but significantly
increased anti-zonulin IgA titre (p<0o0001).  The incidence of
anti-zonulin antibodies during the acute phase of coeliac disease is
consistent with the incidence of other auto-antibodies described in
coeliac disease.  In seven patients with coeliac disease followed
longitudinally, the raised anti-zonulin IgA returned to normal after
3-6 months symptomless remission on a gluten-free diet".

   The serum test for IgA or IgG antibodies in this study is not
identifying a high proportion of those with celiac disease (while there
were strong differences in zonulin levels in the intestinal tissue of
cases as compared with non-cases)!  However, this does not rule out the
possibility that a more sensitive and specific blood test could be
developed in the future - new assays like this often need to go through
a period of refinement.

   Regarding question #2:  I think that the hope is precisely that -
now that a little is known about the disease mechanism (assuming that
this research is correct and is confirmed), maybe that knowledge can be
used for treatment or prevention.  If any useful treatments emerge from
this, however, it will probably be quite a few years before they are
available.

   There was a 2 pg article in last week's issue of "Science News" that
summarized some of this research as well, including a number of quotes
from Anthony(?)  Fasano - several people seemed familiar with his work.
It was published under the somewhat unfortunate title:  "Loosen Up:
Bacterial toxin may lead to less painful treatments for diabetes and
cancer".  Science News Apr.  22, 2000; Vol.  157, No.  17.  The
"bacterial toxin" they are referring to here is cholera, which
chemically resembles zonulin closely.  Science News is written for
intelligent laypeople, and should be available at local libraries.  An
interesting point made in this article is that the zonulin which
influences the blood/brain barrier differs slightly (by a few amino
acids) from the zonulin that governs intestinal permeability.  As now
understood, the intestinal zonulin which is increased in celiac disease
cannot cross the blood/brain barrier and vice-versa, which makes it
less likely that it influences neurological conditions.  But work on
this is definitely in its' infancy, and there is no doubt that there is
much to learn.

   To save some of you time, neither the Lancet nor the Science News
web sites have summaries of these articles.  I haven't had a chance to
check other places on the web.  I'd be glad to post other research
results like these when I run across them.  Again, hope it's helpful.

        Deirdre Hill

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