Dr. R Hoggan wrote:
> Martin Kagnoff ... showed an increase of adenovirus 12 antibodies among
those who had developed celiac disease.
> The investigative focus has now shifted, as you mention, to looking for
signs of prior rotavirus infection.

That's unfortunate, in my view. My thinking is that viral or bacterial
infection can trigger or aggravate celiac disease, but is not a necessary
precondition for the disease to develop, which explains why not all of
Kagnoff's patients had adenovirus 12 antibodies. Once the definition of
celiac disease is broadened, as you rightly indicate it should be, this will
become clearer to scientists. Once celiac disease is recognized as a symptom
of an underlying problem of evolutionary discordance (what I call modern
foods syndrome), as Eaton and Cordain argue, the picture will become even
clearer to scientists.

> The more interesting part of your hypothesis, from my perspective, is the
identification of constituent proteins of
> fibrous or hair-like cells, which may have similar sequences of amino
acids to those found in gluten. Do you know if 
> these protein structures have been characterized? The gluten proteins
certainly have been. ...

Since gluten is composed of fibrous proteins, the answer to your question is
yes. Gluten is a network of intertwined water insoluble fibrous protein
strands (gliadin and glutenin) with water molecules trapped in between.
Gliadin and glutenin contain cystine peptides, which are hair-like/fibrous
amino acids. Cystine is also found in high concentrations in the cells of
the human immune system, skeletal and connective tissues, skin, digestive
enzymes, and hair. 

In searching my files I came across the following from "The Late Role of
Grains and Legumes in the Human Diet, and Biochemical Evidence of their
Evolutionary Discordance," by Loren Cordain, Ph.D., copyright 1999,
http://www.beyondveg.com/cordain-l/grains-leg/grains-legumes-1b.shtml:

	<<... How is it that wheat can wreak such havoc with the [immune]
system? Our research group believes that wheat contains peptide sequences
which remain undigested and which can enter into systemic circulation. THESE
PEPTIDE SEQUENCES ARE HOMOLOGOUS TO A WIDE VARIETY OF THE BODY'S TISSUE
PEPTIDE SEQUENCES AND HENCE INDUCE AUTOIMMUNE DISEASE VIA THE PROCESS OF
MOLECULAR MIMICRY [emphasis mine]. HLA molecules within the macrophage then
present amino-acid sequences of the fragmented peptide to circulating
T-lymphocytes, which through clonal expansion create other T-cells to
"attack" the offending dietary antigen and any other self-antigen which has
a similar peptide sequence--i.e., the body's own tissues. 

	The original non-agricultural HLA haplotypes conferred selective
advantage in earlier evolutionary times because these genotypes provided
enhanced immunity from certain types of infectious diseases. However, with
the advent of cereals in the diet they represented a liability. Thus, the
genetic data clearly shows that a recently introduced food type has resulted
in genetic discordance between our species and those from the gramineae
family.>>

I'll bet that some or all of the peptide sequences that Cordain refers to
here are fibrous protein peptides. In reading this again I realize that
Cordain basically presented the same hypothesis I did, though without making
the specific connection regarding hair-like fibrous protein cells and
without widening the hypothesis to include proteins in other modern foods as
possible triggers (though I'll bet he also holds that view). 

I also searched the Net and came across the following from Dr. Kalle
Reichelt (Kalle Reichelt, M.D., Food and mental problems, 26 Feb 1996,
http://gluten-free.org/reichelt.html), which also proposes my basic
hypothesis regarding mimicry and food proteins, but--like Cordain--does not
mention the hair-like/fibrous protein connection:

	<<There is increasing evidence that components from food do indeed
cause serious psychiatric(9-12) and neurological(13-16) disease. Even
rheumatoid arthritis as such may have a link to food proteins(17) and it
[is] well established that stress (which such a disease is to a very large
extent) increases gut permeability. Nobody denies the possibility of
reactive depression, but there is little reason why this could not be made
worse by dietary factors. Because antibodies are indeed induced by peptides
it may even be so that dietary peptides by mimicry to endogenous cell
surface peptide sequences, may be responsible for many autoimmune
diseases(18).>>

So it looks like I should say that I have expanded on the hypotheses of
Reichelt (1996) and Cordain (1999), rather than proposed a new one.

There is also the "common cause hypothesis" of the Autoimmune Disease
Research Foundtion (ADRF). The ADRF states:

	"Many chronic diseases, like juvenile diabetes and lupus, are
believed by some to have a common cause in a malfunctioning autoimmune
system. The Autoimmune Disease Research Foundtion (ADRF) believes that
autoimmune diseases are really one disease with numerous symptoms that vary
depending upon the parts of the body that are damaged. The ADRF was started
by people who were frustrated by the lack of progress in finding a cure for
juvenile diabetes and other autoimmune diseases." ("Common Cause
Hypothesis," Autoimmune Disease Research Foundation, Retrieved 5/17/05,
http://www.cureautoimmunity.org/Q%20&%20A%20v2.htm)
 
I think that the ADRF is on the money with this. Autoimmune diseases are
really fairly arbitrary groupings of symptoms that focus on one or a few
particular tissues. Often times people will have symptoms from multiple
autoimmune diseases and don't fit neatly into a single disease category.
These patients are said to have an "autoimmune overlap syndrome." What they
really have is symptoms of what I could perhaps term modern lifestyle
syndrome (caused by the effect on human genes of one or more of modern
foods, sedentary lifestyle, toxic chemicals, and microbes--with foods likely
being the biggest factor).

> My own bias is that gluten-induced illness is affecting a much broader 
> segment of the population than the ~1% with celiac disease. Frankly, I 
> think that it was an unfortunate miscue when medical researchers 
> became preoccupied with gluten-induced intestinal damage in the 
> mid-1950s. The evidence clearly shows that there are many people who 
> suffer from a variety, and wide range of severity, of gluten induced 
> illnesses without any identifiable damage to the villous architecture. 
> The artificial restriction of the therapeutic use of this diet to 
> celiac patients is, in my opinion, highly questionable.  ... Today, 
> many symptomatic individuals are never offered a gluten-free diet
> when they do not show the antibodies or damaged intestinal 
> villi that have been associated with celiac disease. 

I agree with you on all of those points. It will require a societal change
from looking at wheat as healthy and celiac patients as inexplicable from an
evolutionary perspective, to looking at wheat as an unhealthy recent
addition to humanity's staple foods and celiac patients as the logical
result of evolutionary discordance due to biologically inappropriate diets.

> Yet these many of these individuals do demonstrate IgG antibodies against
gliadin and they do have a significantly 
> increased risk of neurological diseases, autoimmunity, as well as learning
disabilities and behavioural disorders. 

Yes, if a symptomatic patient gets an "equivocal" (mid-range) gliadin
antibody result, they are usually told it's nothing to worry about (if they
are told anything), until they later develop serious problems such as a
recognized autoimmune disease. At that point the doctor tells them they DO
have something to worry about. Luckily, my doctor believes in trying the
diet with interested, symptomatic patients and generally doesn't bother with
the antibody test because he believes in "treating to the patient, rather
than to the lab," as he put it. Myself and other people I know have improved
remarkably on a gluten-free diet despite gliadin antibody numbers that are
considered equivocal or negative. 

I learned that the gliadin antibody figures that are considered "positive"
have fallen in recent years as knowledge increases, revealing that these are
somewhat arbitrary figures--guesses based on clinical experience. The best
data to provide an optimal baseline would be the gliadin antibody levels in
hunter-gatherers who do not include gluten foods in their diet, rather than
clinical guesstimates based on data from Americans who regularly consume
gluten.

> Your hypothesis, assuming that sequence homology can be demonstrated
between one or more of gliadin sequences and the 
> constituent proteins of hair-like or fibrous cells that you have
identified, may well provide an important insight into 
> this process and a bridge that connects gluten sensitivity in all its
forms, including celiac disease. 

Also, sensitivity to and problems from other "foreign" proteins, such as
casein and whey, may be partly the result of structural similarity to
proteins in human tissues.

> ... Some investigations of the protein
> structures of islet cells are currently under way. 

Yes, islet cell proteins are apparently similar in structure to at least one
of the proteins in cow's milk--bovine serum albumin (BSA). Bovine serum
albumin (BSA) peptide may trigger an autoimmune attack on p69 (also called
69 kDa and ICA69). An islet cell cytosolic protein, p69 is a human beta-cell
surface protein with a similar structure to BSA. 

The presence of antibodies to beta-lactoglobulin (bovine whey protein) in
serum has been identified as a risk factor for type 1 diabetes. Bovine
insulin protein has also been suggested as a possible cause of autoimmune
attacks on islet cells that make human insulin.

	"Studies show that early exposure to cow's milk may encourage
juvenile diabetes. Scientists believe it is because the protein in cow's
milk [bovine serum albumin] is so similar to the molecular structure of
islet cells. Islet cells are the cells in our pancreas that produce insulin.
Because of the close resemblance, our immune system confuses the two and
attacks its own cells by mistake." Not Milk? By LifeDynamix, 01/2004,
http://www.lifedynamix.com/articles/Nutrition/Not_Milk.html

	"Babies' immune systems largely ignore cows' milk proteins that have
been chopped up. However, contact with one intact protein in cows' milk,
bovine insulin, may set off a destructive process, suggest immunologist Outi
Vaarala and her colleagues at the University of Helsinki. The immune system
would attack pancreas islet cells that make human insulin, which resembles
bovine insulin, and would produce antibodies." N. Seppa, Cows' milk,
diabetes connection bolstered, Science News, Vol. 155, No. 26, June 26,
1999, p. 404, http://www.sciencenews.org/pages/sn_arc99/6_26_99/fob2.htm

> I do not know if this work has yet identified any homologous sequences.
But one case was reported in the peer-reviewed 
> literature in which type 1 diabetes was reversed through a gluten-free
diet alone. I consider that to be smoking gun 
> evidence of molecular mimicry. 

Yes, and type 1 is generally recognized as autoimmune. Other diseases of
civilization that I believe also likely contain an autoimmune (and molecular
mimicry and dietary) component, but are not widely recognized as autoimmune,
include type 2 diabetes, acne, osteoarthritis, endometriosis, heart disease,
etc. Any disorder whose cause is listed as "idiopathic" (unknown) is a
likely candidate for having an autoimmune component. Ray Audette even
hypothesizes that obesity is an autoimmune disorder.

> I would sure like to see your
> hypothesis investigated as it could provide another important 
> dimension of understanding of this complex and widespread problem.

Thanks for the interest and input, Ron.