New Insights into Allergen-Specific Immunotherapy in Rhinitis and Asthma

Allergen-specific immunotherapy (SIT) was introduced on an empirical basis about a century ago [1], with the erroneous rationale of vaccinating against “airborne toxins.” Despite this wrong conception, the subcutaneous injection (SCIT) of pollen extracts proved capable of reducing the symptoms of hay-fever, and SIT (also termed “vaccine”) became one of the cornerstones of allergy treatment. After the discovery of IgE [2], the mechanisms of SIT were investigated and its clinical efficacy was assessed in double blind placebo controlled trials [3]. From the 1960s until the end of the 1980s, there were no important changes in the practice of SIT that was invariantly given by SCIT, other than the introduction of the modified allergens or allergoids. In 1986, the British Committee for the Safety of Medicines (CSM) [4] reported 26 deaths due to SCIT and started a process of intense critical revision of this treatment, which led to the publication of the World Health Organization guidelines [5]. In these guidelines, indications, contraindications, risks, and benefits of SCIT were clearly stated, and SCIT was finally recognized as an effective treatment.

Another important consequence of the CSM report was the strong impulse to search for safer modalities of immunotherapy. In this regard, the sublingual route (SLIT) was extensively studied and subsequently validated [5, 6]. SLIT can, therefore, be considered an important milestone in the history of SIT, since it really changed the clinical practice and originated an intense debate, which is still ongoing. Another revolution in the history of SIT was the discovery of Th1 and Th2 lymphocyte subsets [7], which allowed elucidating the mechanisms of action and, in turn, opened new research pathways such as the use of adjuvants. Few years later, the T regulatory cells were also described [8], leading to new immunotherapy approaches. In parallel to the clinical evolution, basic immunology techniques also evolved rapidly and provided the instruments to design and build specific molecules, such as the recombinant and engineered allergens, for immunotherapy (Fig. 1).