00:01
Atopic allergy can be diagnosed using the skin prick test, where
small amounts of the suspected
allergen are injected under the skin.
00:10
This leads to the release of inflammatory
mediators from any mast cells that
have been pre-sensitized with IgE
antibody against the suspected allergen.
00:23
This will lead to vasodilation and edema causing the
characteristic wheal and flare response that is detected as a
response to the suspected allergen, if that proves to be the
allergen that is responsible for the patient’s symptoms.
The amount of IgE specific for a
particular allergen that is present in
a patient can be measured using the
allergen specific IgE test or RAST.
In this test, the allergen is immobilized on a disc or
some other surface, and then patient’s serum is added.
If the patient has antibodies that are specific for the
allergen, then those antibodies will bind to the allergen.
If the antibody is IgE antibody, it can be
detected using a labeled anti-IgE antibody.
In the past, the label most commonly
employed was a radioactive isotope.
Hence, the name of this test, RAST which
stands for radioallergosorbent test.
However nowadays, most commonly instead of using a
radiolabel, some other type of detectable label is used.
For example, an enzyme that causes
a colour change in a substrate.
What are the therapeutic
options for allergy?
Well of course the easiest approach is
to remove or avoid the allergic trigger.
If you are allergic to the cat, then it would be a
good idea maybe to give your cat away to a friend.
If you’re allergic to pollen,
don’t go out in the spring time.
Of course this is very easy to say,
it’s much harder to achieve in practice.
But where possible, avoidance
of the allergen is the best.
And if you’re allergic to a particular
food, it may not be too difficult
to avoid exposure to that food as long as you know what it is.
02:28
If removal or avoidance of the allergen is not
practical, then one can use H1 blockers, mast
cell stabilizers, anti-inflammatory corticosteroids
and leukotriene inhibitors or immunotherapy.
02:48
Another approach is to use a monoclonal antibody
that is specific for the IgE class of antibody.
02:56
This particular antibody,
omalizumab, is specific for IgE.
03:02
And when injected into the patient, the antibody binds
to IgE and removes it from the patient’s circulation.
03:12
And therefore mast cells
do not get sensitized.
03:16
It also has a secondary effect of reducing the number
of FcεR1 receptors on the surface of mast cells,
because it turns out there’s a feedback mechanism
where the less IgE there is, the less FcεR1 there is.
03:32
So it has a doubly beneficial effect.
03:35
And we can see here, the antigen
activated mast cell, or basophils
in the circulation can also release
these inflammatory mediators.
03:44
And by using this monoclonal antibody
against IgE, you can block this activity.
03:52
Cromolyn is a mast cell stabilizer
that prevents mast cell degranulation.
04:00
And here you can see the cromolyn is
blocking the release of mast cell mediators.
04:07
Leukotriene antagonists such as
montelukast, can block bronchial
constriction caused by leukotrienes, here shown on this diagram.
04:19
β-adrenergic agonists such as albuterol
can stimulate bronchial relaxation.
04:27
And finally, corticosteroids can suppress
transcription of pro-inflammatory genes.
04:35
Histamine does not play a significant role
in bronchial constriction, and therefore
antihistamines such as H1 receptor
antagonists are not used to treat asthma.
04:56
One potentially very beneficial approach to the
treatment of allergy is to use immunotherapy.
05:04
And this is used for allergens that are hard to avoid such
as pollens, house dust mites, molds, insect venoms and so on.
05:13
It involves the subcutaneous injection of small
amounts of allergen in gradually increasing doses.
05:22
These are increased weekly or biweekly by two or less
times until the maximum tolerated dose is reached.
05:31
That is the dose at which symptoms begin
to be seen in response to the injections.
05:38
The patients are observed for 30 minutes post injection
during dose escalation due to the risk of anaphylaxis.
05:46
Alternative routes of administration include
sublingual and oral rather than subcutaneous.
05:53
And the way in which these allergen immunotherapies
work is by shifting the immune response away
from the Th2 IgE mediated type of response and by
increasing the activity of regulatory T-cells.