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Desensitization
for alopecia areata
Desensitization has been used for several years to treat people
with severe allergies. It simply involves injection of the allergen
in volume into the affected individual. How the body responds
is an area of argument, but the result is the body's immune system
becomes non-repsonsive to the injected alergen. The essential
idea of desensitization for allergies is to either delete IgE
producing B cells, force
the
B cells to switch to a different Ig type of production, and /
or to induce suppressor / regulatory cells to regulate the B cell
antibody production and T lymphocyte activity. Desensitization
has been suggested as a potential treatment for alopecia areata
if
we can define the particular hair follicle antigen that is the
target
of the inflammatory cell attack.
Hair follicle autoantibodies in alopecia areata are of the IgG
isotype. We have not found any other antibody type so far. Potentially
injection of large amounts of antigen to which you have IgG antibodies
may be dangerous. It may lead to anaphylactic shock as occasionally
occurs with antigen desensitization for other allergies. Alternatively,
desensitization may actually promote a renewed attack on hair
follicles.
I do not believe desensitization using high dose antigen adminsitration
will be become an effective, reliable or practical treatment for
alopecia areata. At least not without a lot more research.
Oral
tolerance for alopecia areata
Oral tolerance takes advantage of some rather unique properties
of gut associated lymphoid tissue (GALT) that has a very strong
suppressor function (among many specialized functions) and promotes
acceptance of foreign antigens. Of course it has to because we are
putting foreign food antigens into our stomach every day and break
down products are absorbed into our blood stream in the gut. So
there must be some method to make sure the immune system does not
react to these foreign food antigens. Trying to manipulate the GALT
system to enable tolerance to a number of autoimmune conditions
has been an expanding area of research over recent years.
The technique of oral tolerance simply involves regularly ingesting
a quantity of antigenic tissue to which the immune system is responding
in an autoimmune disease. For example in one study people with rheumatoid
arthritis were given daily doses of chicken collagen. This oral
tolerance apparently helped reduce pain and control the arthritis
but did not cure the condition. It seems that the GALT looks at
the collagen and then advises the rest of the immune system that
it is food and therefore not a threat. The rest of the immune system
apparently takes some notice and joint inflammation is reduced accordingly.
There are some problems in developing oral tolerance for use
in alopecia areata treatment. A) Researchers don't know exactly
the
component of hair which is targeted by the body and that they
have to pin that down first. B) The hair follicle is heavily
keratinized
and if the body is responding to the keratin, there is a problem,
because keratins are insoluble and they would have to be soluble
to be absorbed orally in the gut. Insoluble hair keratin is irritating
to the stomach lining and may actually induce gut inflammation.
C) A further problem may be ensuring that correct dosage levels
of the antigen(s) the immune system is reacting to are given.
With
oral tolerance there seems to be a "window" where the supply of
antigenic material works best. Too much or too little may not
have
the desired effect. One may not need to pin down the exact antigen(s)
but one will need a rough idea of where they reside to develop
suitable
dosage concentrations. D) Probably more than one antigen is involved
and the targets may differ for different individuals. E) Obtaining
enough hair follicle material for use. Completely keratinized
hair fiber will not work (I think) as the immune system does
not target
this dead material - it goes for the living cells at the root
of the follicle and/or the sheath cells surrounding the fiber.
Keratinization
may also hide some of the residual antigens in the hair fiber.
Obtaining enough of this antigenic material may mean resorting
to non-human
tissue and there the question is are the antigens the same as
in human hair follicles. The alternative is synthesize protein
sequences. This can be done, but to produce large amounts is currently
quite expensive.
Desensitization
and oral tolerance for alopecia areata references
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Yoon CH, Min JK, Lee SH, Park SH, Kim HY. Antigen-induced, tolerogenic
CD11c+,CD11b+ dendritic cells are abundant in Peyer's patches
during the induction of oral
tolerance to type II collagen and suppress experimental collagen-induced
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PMID: 11899422
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PMID: 11244033
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