I appreciate Jenny's recent comment about my original posting on
molecular mimicry. Having had a busy weekend, I didnt get a chance to
answer, but upon my return, I see that Ward Nicholson has done a
superb job in covering this topic. My only follow-up on this idea
concerns the genetic evidence which supports the concept.
In the human immune system, there are a number of individual mechanisms
which allow the body the ability to determine self from non self so that
foreign proteins (ie bacteria, viruses etc) can be recognized,
destroyed and eliminated. Perhaps the most complex system which nature
and evolution have engineered to accomplish this is the human leucocyte
antigen (HLA) system. This system was discovered when early physicians
found out that tissue from one human could not be grafted to another
without rejection. The physiological function of this system was not
to foil the efforts of transplant surgeons, but to initiate an immune
response to parasites (viruses, bacteria). All cells of the body
manufacture HLA proteins, whose function is to bind short peptides
(protein fragments) and display them on the cell surface. Most of the
peptides are derived from the body's own proteins (self peptides),
however when the body is infected by a virus or bacteria, the HLA
molecules pick up peptides derived from broken down proteins of the
virus or bacteria and present them to T lymphocytes. The purpose of
T-lymphocytes is to continually scan the surfaces of other cells to
recognize foreign peptides while ignoring self peptides. Once a T cell
receptor "recognizes" a foreign peptide, a complex series of steps is
set into play which ultimately destroys the cell presenting the foreign
peptide as well as living viruses or bacteria in the body which also
have peptide sequences similar to those which were presented. When
the HLA system loses the ability to recognize self (self peptides) from
non-self (foreign peptides), T- lymphocytes attack self tissue
resulting in what is known as an autoimmune disease (i.e. celiac
disease, IDDM, MS, Dermatitis Herpetiformis, ankylosing spondylitis
etc).
The HLA proteins which present foreign peptides to circulating T
lymphocytes are coded by DNA sequences on chromosome 6. The entire
HLA system includes more than 100 genes and occupies a region more than
four million base pairs in length which represent 1/3,000 of the total
human genome. On chromosome 6, the HLA is sub-divided into Class I
(HLA-A, HLA-B, HLA-C) and Class II segments (HLA-DR, HLA-DQ, HLA-DP).
Individuals with autoimmune disease inherit characteristic HLA
combinations which identify their disease. People with celiac disease
have genetic markers (HLA-DR3, HLA -B8 and HLA-DQ2) which are associated
with the disease; people with insulin dependent diabetes mellitus
(IDDM) almost always have DQ and DR genotypes. Thus, the manner in
which foreign proteins are presented to circulating T cells by HLA
proteins tends to be different for individuals with auto-immune diseases
compared to those without these maladies.
As I mentioned in a previous post, the incidence of a variety of
autoimmune diseases follows a southeasternly gradient from northern
europe (highest incidence) to the mideast (lowest incidence) - can
provide citations if wanted. This gradient occurs because the
incidence of susceptible HLA haplotypes increases as one moves north
westerly from the mideast. This gradient which occurs for both the
incidence of autoimmune diseases and HLA haplotypes is not a
serendipitous relationship but occurred as a result of the spread of
agriculture from the mideast to northern europe (Simoons FJ. Celiac
disease as a geographic problem. In: Food, Nutrition & Evolution. DN
Walcher & N Kretchmer (Eds), NY Masson Pub, 1981, 179-199).
Consequently, as agriculture spread into Europe there were environmental
elements associated with this demic expansion which progressively
selected against HLA haplotypes (combinations of HLA genes inherited
from the two chromosomes in each cell) which were originally present in
the pre-agrarian peoples of Europe. Now, the question is, what were
those environmental selective elements? In the case of celiac disease,
it doesnt take a rocket scientist to determine that it was wheat.
Increasing consumption of wheat caused increased mortality from celiac
disease - thus, the incidence of celiac disease and its susceptible HLA
haplotypes (HLA-B8, HLA-DQ, HLA-DR) are lowest in those populations with
the most chronologic exposure to wheat (mideasterners and southern
europeans) and greatest in those populations with the least exposure
(northern europeans). Similar arguments can be made for IDDM and a
host of other autoimmune diseases. There are a substantial number of
animal studies showing that consumption of wheat by rats increases the
incidence of IDDM - citations available if wanted.
How is it that wheat can wreak such havoc with the autoimmune system?
Our group believes that wheat contains peptide sequences which remain
undigested and which can enter into systemic circulation. These
peptide sequences are homolgous to a wide variety of the body's tissue
peptide sequences and hence induce autoimmune disease via the process of
molecular mimicry (eg. macrophages ingest the circulating wheat
peptides and HLA molecules within the macrophage 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 bodies own tissues). The original
non-agricultural HLA haplotypes conferred selective advantage 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.
Cordially,
Loren Cordain, Ph.D.
Professor, Colorado State University
-And yep! I'm not a her, but a him!
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