<<Disclaimer: Verify this information before applying it to your situation.>>
In comparing the work to identify a dominant gliadin eptitope in the
following 2 studies, I noted that the amino acid sequences of the
identified gluten peptides differed:
In vivo antigen challenge in celiac disease identifies a single
transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope
Robert P. Anderson, Pilar Degano, Andrew J. Godkin, Derek P. Jewell, Adrian
V.S. Hill
Nature Medicine 6, 337-342 (01 Mar 2000)
Structural Basis for Gluten Intolerance in Celiac Sprue
Lu Shan, Øyvind Molberg, Isabelle Parrot, Felix Hausch, Ferda Filiz, Gary
M. Gray, Ludvig M. Sollid, and Chaitan Khosla
Science Sep 27 2002: 2275-2279
Upon further review of these articles, I note that two different alpha-
gliadin polypeptides were used in the 2 studies, each made up of a
different amino acid sequence. In fact, there are many variants of
gliadins:
Coeliac disease: dissecting a complex inflammatory disorder
Ludvig M. Sollid
Nature Reviews Immunology 2, 647-655 (01 Sep 2002)
"Wheat gluten consists of a complex mixture of many gliadin and glutenin
polypeptides. Gliadins are monomers, whereas glutenins form large polymeric
structures. On the basis of their amino-acid sequences, gliadins can be
subdivided into a alpha-, gamma- and omega-gliadins, and glutenins can be
subdivided into high-molecular-weight glutenins and low-molecular-weight
glutenins . Many variants exist of each polypeptide type, with the greatest
variation being of the gliadins."
It is entirely possible that if the 2 studies were replicated using the
same alpha-gliadins, the 2 studies would identify the same gluten peptides,
thus resolving the differing results. In fact, the 17-amino-acid sequence
of Robert Anderson's peptide essentially makes up the first half of Lu
Shan's 33-amino-acid sequence. But this means that if a treatment for
celiac disease is to be developed, how many different alpha-gliadins and
dominant gluten peptides must be identified and considered?
The 2 studies use 2 different methods to identify dominant gliadin
epitopes. So rather than the studies yielding a definitive gluten peptide,
they simply provide the tools and lay the groundwork for identifying all
possible gluten peptides. There is obviously much more work to be done.
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Responses to my previous post include this one from Kelly Rohlfs:
"I am the volunteer who is helping Dr. Khosla raise money for celiac
research for the lab in Sunnyvale, CA. Yes, there are different approaches
to finding a cure. Dr. Khosla has listed them on his website,
http://celiacsprue.org/drugprograms.html . He does intend to pursue all
paths and is in contact with researchers around the world."
The Celiac Sprue Research Foundation lists 3 approaches being considered
for treating celiac disease, including the bacterial enzyme approach which
was prominantly featured in press releases. The other 2 approaches have
been entirely overlooked by the press. You should, therefore, not believe
that enzymes are the only treatment being considered by this group. All 3
approaches are discussed and explained in more detail in the following
Science magazine editorial which accompanied the above article:
Gluten and the Gut--Lessons for Immune Regulation
Detlef Schuppan and Eckhart G. Hahn
Science Sep 27 2002: 2218-2220
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Another response:
"I am intrigued by these approaches to making gluten safe for we poor
folk. I've got a couple of comments on your discussion.
Firstly, I talked to a wheat breeder about making "safe gluten" wheat. She
suggested that the large number of different glutens would be a huge
impediment to finding the responsible ones and breeding them out would be
an enormous task. I think it would be worth it, personally, every time I
pass the pastry aisle at Safeway. Once you have safe-gluten wheat, you
then have to keep it separate - here in Canada we have a characteristic
that wheat must have called Kernal visual distinction or some such (KVD for
short, I think) which means that wheat of different classes must be
distinct. If this safe-gluten wheat is bred with its own KVD, then cross-
confusion with evil wheat would be less common - however, accidents will
always happen. I'm hoping that the separation manditory for some GMO crops
will pave the way for keeping the good grain from the bad (that goes for
evil wheat and and other crop we currently can eat, too!).
The second point is about eliminating the effects of evil wheat (I love
that term!) on celiacs. I'm in the camp which says a lactase-type pill
isn't going to work - enzymes are never 100% effective, so some gluten is
always going to get in. If a pinch is really as bad as a pound, then an
enzyme is never going to work. I like the idea of having it when you go to
a restaurant so you can mop up any extra gluten, but it'll be a while
before it is cheap enough to use regularly. My boyfriend raised the point
that we don't actually know if a pinch is as bad as a pound, or that it is
for everyone. I think that if it is, it's because of the immune cascade
that goes on, it'd be interesting to hear what you think after your
research.
So, right now I'm putting my money on the T cell inhibitor, above safe
wheat and glutenase."
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And, finally this response:
"Remember they could both be correct. There may be more than one toxic
sequence. Celiac disease may be more than one disease, as cancer is now
known to be. Certainly there is a wide variety of clinical expression in
CD, with the only commonality being villous atrophy. And there is no one-to-
one correspondance between a particular genome and occurrence of CD, which
hints at complexity. Even gluten as a triggering agent has not been shown
to be universal in CD; witness the phenomenon of refractory sprue.
I would regard all of this as basic research, with the possibility of
treatment anytime soon being purely speculative. It usually takes decades
for practical technology to result from new basic discoveries. So I would
focus on this as fascinating new knowledge, rather than a promise of
a "cure"."
*Support summarization of posts, reply to the SENDER not the CELIAC List*
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