<<Disclaimer: Verify this information before applying it to your situation.>>
Causes of CD
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There are three factors involved in CD:
* the immune system
* environment
* genetics
The immune system comes into play through the lymphocytes we
previously discussed. There are lymphocytes in the intestines of
celiac patients that respond specifically to something in gluten.
These are called T-cells, and are actually responsible for the damage
in the villi. There are also cytokines, which are chemical messengers
floating around that our bodies produce to fight infection. The
lymphocytes also produce cytokines which cause even more damage.
The environment comes into play in the form of gluten. For example,
in the early '70s there was a trend towards a macrobiotic diet,
meaning a lot of grains. As a result, a lot of people presented with
celiac disease. This was a result of challenging themselves with a
lot of gluten, causing the damage in the intestine to become more
extensive. So a gluten challenge can cause symptoms, though Dr.
Murray does not think it triggers the disease itself. Instead, some
other event may "trigger" the beginning of CD. Possible triggers of
CD include:
* A significant change in nutritional status (such as deciding to
lose weight).
* An infection. Any kind of infection can inflame the lymphocytes
in the intestine so that they start responding, possibly to
gluten.
* The aftermath of pregnancy. During pregnancy the body's immune
system must be prevented from responding to the fetus, which is a
foreign organism that is immunologically separate from the
mother. So the immune system is suppressed to accommodate that
foreign being. Immediately after delivery the immune system
reconstitutes and raises its defenses. What happens is that any
kind of autoimmune disease can get worse after delivery, and one
of these is CD. Many of Dr. Murray's patients' symptoms started
after childbirth; though not necessarily after the first child.
Sometimes symptoms would start after the second, third, or even
fourth child.
DH is different and often gets worse during pregnancy, not
afterwards. It is not clear why, though it is thought to have
something to do with changes in the skin.
* Surgery. It is thought that this also has something to do with
stimulating the immune system.
There is a tissue type called HLA. This is similar in nature to blood
types, where A, B, and O are the three standard blood types. Tissue
typing takes that a whole generation further, taking it down to very
specific subtypes of the genetic material in our white blood cells
(and most other cells in the body). It identifies us as "self",
because we have a specific genetic type in our cells. Our body uses
this to avoid attacking anything that it can identify as "self";
anything else it readily attacks. This is what makes organ
transplants difficult. The body automatically recognizes the
transplanted organ as a foreign body and tries to attack it as an
invader. It is the immune system that mounts this attack, and one of
the things it uses to distinguish foreign bodies from "self" is the
HLA typing in the body's cells.
Why is this relevant for celiacs? There is a very particular tissue
type that is seen in most celiacs called DQ2. (Dr. Murray noted that
the HLA names keep changing every year or two, so that a different
term might be in use now; but DQ2 was what it was previously called.)
Studies in the USA on this subject are sparse, but in studies in
Czechoslovakia, the United Kingdom, and Italy 87% or more of the
celiacs had this tissue type.
The risk of CD increases within the families of known celiacs.
According to Dr. Murray, here are the approximate risk factors for
various relatives of a diagnosed celiac:
-- identical twin: 70% (but not 100%, thus proving CD is not
entirely genetic)
-- HLA-matched sibling: 30-40%
-- non-HLA-matched sibling: 10% (some say even 20%)
-- child: less than 10%
-- parent: 5-7%
-- others (nieces, nephews, grandparents, grandchildren): even less
likely
Why is there a difference in risk factors for an identical twin and an
HLA-matched sibling? Clearly there must be another gene involved
besides the known DQ2 tissue type. Up until three months ago we
didn't have any clue as to what that other gene might be. But at the
symposium in Finland<1> a collaborative study done jointly in Galway,
Ireland and Alabama, USA provided some new information. A series of
families from the Galway group were studied. A new method of looking
for gene site associations was used. They took some of the
chromosomes from blood samples of these patients and looked for
genetic similarities. [Human beings have 23 pairs of chromosomes.
Each chromosome is composed of a multitude of genes.--editor] They
found one spot on chromosome #6 which it seemed to be very highly
associated with CD; in other words, those that have CD seem to have
this "spot" on chromosome #6; those that did not have CD did not tend
to have this "spot". It is not known what the genes in that "spot"
do, because i t is one of those uncharted areas of human genetics. It
is hoped that over the next two years we will learn which specific
gene is involved and how it confers a risk for CD. So there are
probably at least two separate genes that come together to result in a
genetic predisposition towards CD.
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