E. Scala Experimental Allergy Unit, IDI-IRCCS, Rome, Italy Molecule-based diagnosis and allergen immunotherapy Summary Allergen immunotherapy (AIT) represents the only way to modify the natural history of allergic diseases. Unfortunately, AIT is not always followed by a reduction in symp- toms. The main reasons for such failure can be inadequate diagnosis and/or the poor treatment. In both cases, an incomplete or insufficient understanding of the compo- nent(s) responsible for the IgE sensitization on the one hand, and, on the other hand, the lack of a steady and reliable allergen mixture to be used for the desensitization process, could explain unsuccessful treatment. A more comprehensive IgE reactivity profile evaluation of the patient can be achieved by means of a molecule-based diag- nostic approach, in order to distinguish genuine from panallergen-driven antigen recognition. At the same time, a better delineation of AIT products by means of molec- ular dissection, can allow a stronger correlation between diagnostic findings and im- munotherapeutic intervention, thus facilitating the right prescription to the right pa- tient Key words Allergen immunotherapy, allergen molecules, component resolved diagnosis, molecular allergology Corresponding author Enrico Scala Experimental Allergy Unit, IDI-IRCCS Via dei Monti di Creta 104 00167 Rome, Italy Tel.+39 06 6646 4788 Fax: +39 06 6646 2430 Email: e.scala@idi.it Introduction Allergen immunotherapy (AIT) is the only treatment that can change the natural history of allergic disorders (1). For some allergens, an extremely high prevalence of effi- cacy is observed, such as in the case of Hymenoptera ven- om desensitization (2), but this is not always the case. Unfortunately, AIT sometimes fails and patients, despite years of expensive treatment, have no measurable benefit. The reasons for such a failure could be bad diagnosis and/or bad treatment. The lessons learnt from the hundreds of studies per- formed in the last 15 years is that, in order to properly manage a patient, the appropriate treatment should be de- cided on and offered only after performing a comprehen- sive diagnostic workout. Currently, a valid diagnosis in al- lergic disease requires the demonstration of a genuine sensitization to a given biological source, before suggest- ing AIT. A recent report demonstrated how the molecular diagnostic approach could result in a marked change in about 50% of the cases of AIT prescription, in compari- son to the “classical” diagnostic procedures (3). On the other hand, a reliable AIT should be, as the name suggests, “allergen-specific”, and, clearly, AIT effective- ness relies on the fact that all genuine causative allergen(s) should be equally and constantly represented within the treatment chosen for desensitization (4). Bad diagnosis The main purpose for an allergy specialist is undoubtedly to identify an accurate patient IgE reactivity profile. It is widely known that reactivity to a given biological source is Eur Ann Allergy Clin Immunol VOL 45, SUPPL. 2, 25-32, 2013