How does sublingual immunotherapy work?

There is now a growing consensus that specific sublingual immunotherapy (SLIT) does actually work. Initial skepticism about the results of uncontrolled or open studies has been removed after the positive outcomes of a series of large, double-blind, placebo-controlled trials. A recent meta-analysis found 21 trials of SLIT that were of sufficient quality to merit analysis of their efficacy against allergic symptoms. Although there are some differences in dosing, patient selection, and outcome measures, the overall effect of SLIT was found to be beneficial, both on symptoms and on rescue medication requirements. This meta-analysis did not include data from the latest series of large-scale studies to be published, namely those assessing the grass pollen tablet that has recently been granted a product license and marketed in Europe under the trade name Grazax. However, it is interesting to note that the Grazax studies show a degree of efficacy almost identical to that found in the meta-analysis, and therefore when these newer studies are eventually included in a future meta-analysis, the overall effect size will remain much the same. If one accepts that SLIT works, it is then relevant to ask how it works. This has an important bearing on our understanding of how to improve current forms of SLIT and to predict those who are going to respond but might also shed some light on the mechanisms of conventional subcutaneous injection immunotherapy (SCIT). Within the allergy community, we sometimes forget that we do not really know how conventional immunotherapy works. After all, the regimens that we currently use were invented between 1890 and 1930, long before the discovery of IgE or the cytokines that underpin the development of allergy and its clinical expression. Back in the 1930s, it was observed that patients undergoing SCIT had antibody responses to the injected allergen. These were described by Cooke et al as blocking antibodies on the presumption that they might in some way block the access of the allergenic proteins to their targets. Subsequently, we have learned that many of these