The importance of non-IgE and IgE-mediated controls and the
enigma of non-responder basophils
The most frequently used stimulants in the BAT are allergens. However,
basophils of approximately 10% of the population do not respond to
stimulation through FcεRI even though they express normal densities of
cell-surface IgE and upregulate CD63 well to a non–IgE-dependent
stimulus. One cause of non-responsiveness is a low level of Syk
phosphatase21-23, possibly in combination with
elevated amounts of CD4513. The non-responder phase is
transient; a patient may revert to a responsive state within
months24,25. The non-responder state has also been
reversed experimentally in vitro by culturing basophils in the presence
of IL-326. In a large study performed in Singapore,
basophil non-responsiveness was associated with lower amounts of
basophil Syk, and an apparent reduction of the incidence of rhinitis;
basophil non-responsiveness thus may be a final barrier of the immune
system to prevent unwanted reactions against
allergens24. As the amount of allergen-specific IgE
increases, the amount of basophil Syk is transiently decreased by
allergen exposure to limit the allergic response. It is not clear at
this time, however, whether it is the clinically relevant allergen that
is modulating this basophil response.
It is important to document that the blood basophils are alive and
capable of mounting a response to a non-IgE stimulus to document, i.e.
that the activation test is valid. The bacterial tripeptide fMLP that
activates basophils through the G-protein coupled fMLP receptors to
degranulate, is often used as a non-IgE mediated positive
control1. Degranulation through fMLP occurs faster
that the IgE-mediated response. It is insensitive to inhibitors like
Staurosporine and Wortmannin, that inhibit IgE-mediated
degranulation27. After confirming that blood basophils
respond to fMLP, it is important to assess whether they respond to
IgE-mediated controls. Blood basophils of non-responders do not get
activated in response to a stimulus through IgE/FcεRI, i.e. they do not
upregulate CD63 or release histamine.