Subcutaneous works, so the question is, why does it matter? Dr. Derebery said. Well, people don’t like taking shots.
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December 2006The mechanism of action requires that there be antigen contact with oral mucosa long enough for the therapy to work. The antigen is subsequently captured by dendritic cells, matures, and migrates to the lymph nodes, where the nodes then produce IgG-blocking antibodies and immunosuppressor T-cells.
There is an immune deviation toward a T-reg cell response, she said. With the T-reg cell response we get the secretion of ILT and [transforming growth factor beta] and these two cytokines are quite important. They induce antigen-specific IgG4 production and IgA production, causing the suppression of the affector cells…while the cytokines cause decreased production of IgE antibodies as well. So that is the desired state we want.
T-reg cells control and establish the allergic response. They are important for the induction of the T-cell response to antigens or to self-tissue.
We know that in the animal model, sublingual immunotherapy does indeed induce mucosal tolerance, but does it stimulate these T-reg cells? Is there something different about this if we give it sublingually? Dr. Derebery said. Officially, we say it is not known yet, but the recent literature review I did for this presentation indicates it probably does.
One study recently showed that efficacy after sublingual immunotherapy continued five years after it had been stopped and no deaths have ever been reported form administering the drug this way. However, there are limitations.
The trials have always been conducted on mono- or duo-sensitized patients, she said. In English that means they’re being treated with one or two extracts, and many extracts are not biologically compatible. This is good for kids, but what about the adult who typically is polysensitized?
Host Response to Allergens
Dr. Boyd ended the session by talking about the host response to allergens via the TH2 lymphocyte pathway.
At birth, we all have an abundance of TH2 cells…so why are we becoming more and more allergic? he asked. One possible explanation is the hygiene hypothesis-if you are not raised around dust mites and dirt and other children, then your immune system is never going to be fully flipped over. The TH2 cells are not unlike unsupervised adolescents with too much time on their hands.
Dr. Boyd said that children who grow up on a farm or are in day care with other children are forcing the TH2 cells in their bodies to go to work fighting off invaders. For children raised in a spic-and-span environment, without any exposure to dust or other issues, the defenses never develop as well.