Could the large number of indications obtained by the above-mentioned works be translated into the allergists’ practice? At present, the answer is “yes” based on well-established data and “no” based on the uncertain aspects. Until now, no studies have been performed to the authors’ knowledge that have randomized patients’ AIT into two separate groups: one receiving an AIT prescription based on standard diagnosis and the other by adding MBD. In the second group in particular, rules to be used to define AIT should be similar those recently suggested . In the absence of such a controlled study, the only evidence we have is the work of Schmid-Grendelmeier , who showed in an observational study that people with genuine sensitizations had better results than the group with IgE directed to cross-reacting components. One could argue that such a study has many intrinsic defects because it is observational and includes no defined control. Of course, an experimentally controlled and randomized study should be much more relevant to define the problem.
Despite these uncertain aspects, in the last 8 years, many authors have suggested indications regarding the strategy to be followed in prescribing AIT. Valenta et al.  indicated that MBD could support the optimal selection of pollinosis patients for AIT, at least in the Mediterranean area, and they also suggested what the central role of MBD is in monitoring the effects of AIT. The principle was simple and effective. MBD allows the identification of IgE directed to genuine components, such as Phl p 1 or Phl p 5, and to the cross-reacting components Phl p 7 and Phl p 12. The documentation of a genuine reactivity clearly indicates an AIT directed to those allergens. The documentation of an IgE reactivity against cross-reacting components not only explains the large number of allergens that resulted positive in SPT and IgE tests, but, in particular, it explains why AIT avoids allergens whose positivity was only due to a cross-reaction. These rules were further well defined by Moreno et al. . With regards to the use of MBD in the follow-up, Sastre recently described that an adverse reaction can be associated with a certain “molecular” profile of patients treated with AIT .
Asero recently suggested to use Art v 1, Amb a 1, Par j 2, Bet v 1, Ole e 1, Pla l 1, Cup a 1, Phl p 1 and Phl p 5 as markers of primary sensitization to mugwort, ragweed, pellitory, birch, olive, plantain, cypress, and Phleum pratense pollens . The presence of reactivity to these “genuine” components supports the indication to use AIT. This situation is easy to manage in the large number of cases in which one or a few allergens react with IgE. Nevertheless, in poly-sensitized patients, the situation could be much more complex . To further indicate this complexity, the European and the American approaches should be carefully considered, as discussed recently . In this context, the European school always suggests not to exceed the number of three different allergen sources for AIT in the same patient, while the American school treats patients with a mixture of all the positive allergens. Of course, advantages and disadvantages are apparent in these two approaches. In addition, it is evident that MBD was accepted enthusiastically and used by Europeans but was only barely recognized by Americans.
Special care should be paid in specific situations that are different from the previous examples. Even if the case is very rare, it is possible in a mite allergy that positive SPT and sIgE are associated with a pure sensitization to tropomyosins , a component family that shares allergens between mites, cockroaches, shrimps, snails, etc. AIT for mites does not contain Der p 10 (the mite tropomyosins) , and for this reason, its administration would be useless, at least if an immune reaction to tropomyosins is expected. Thus, the indication for the correct AIT is achieved by the collection of an accurate patient history and by the molecular assay with Der p 1, Der p 2, Der f 1, Der f 2 and Der p 10.
The introduction of the MBD is also changing the follow-up of treated patients. Indeed, it has been shown that severe reactions to olive AIT may occur in patients sensitized to Ole e 7 and Ole e 9 , and other similar reports are expected in the future.
Asero  and others  reported that AIT is equally effective in patients with single or multiple sensitizations if the administered allergen is carefully selected. Other authors have suggested simple and probably effective rules, although this observation has never been demonstrated with a properly designed clinical study. For example, Luengo stated that in the case of sensitization to the crude extract SPT and/or positive sIgE, AIT indication would be invisible if all components were negative because the extracts would be unlikely to contain the sensitizing molecule . Finally, based on data from microarray allergen diagnostics (ISAC), Melioli et al identified 4 different clusters of patients with different reactivities . The first was characterized only by a reactivity to genuine molecules, the second to genuine and few cross-reacting molecules, the third to both genuine and cross reacting molecules, and the fourth virtually only to cross-reacting reactive molecules. In an expert system to support the interpretation of ISAC results , these groups were implemented, and the potential capacity to be responsive to AIT is immediately calculated by the program. With regards to the use of allergen microarrays in clinics, too many concerns have slowed down their use in clinical practices, such as the high cost and the risk of unexpected results. In regards to the cost, a thorough investigation of the IgE profile using a single-plexed allergy diagnosis may be even more expensive in polysensitized patients. Unexpected results are mainly due to an unknown sensitization or to an incomplete collection of a patient’s history. However, many other relevant added values can be obtained from allergen microarrays. In particular, a clear picture of the sensitization profile is achieved, thus allowing the patient’s phenotyping; furthermore, the explanation of possible discrepancies between SPT or specific IgE results and ISAC are given. Then, multiplexed data allow the distinction between the sensitization to one or a few components of a cross-reacting allergen family and, in many cases, the identification of the first sensitizer is also suggested. Finally, an exhaustive IgE profile can be useful in pediatric or adolescent patients to follow-up the allergenic march at the molecular level .
An interesting and poorly explored context for molecular diagnosis is respiratory occupational allergy. Respiratory occupational allergy is a relevant problem, and it causes disabilities and socioeconomic consequences for both the patient and society. It is probably still underdiagnosed. A correct diagnosis is extremely important to reduce or limit the consequences of the disease. In any adult whose asthma or rhinitis begins or worsens while working, a diagnosis of respiratory occupational allergy should be considered, and a detailed occupational and medical history should be collected. All workers should be asked whether symptoms improve on days away from work or on holidays; positive answers should lead to further investigation. MBD helps to distinguish between sensitization to occupational exposures and cross-reactivities. Some important causes of occupational allergy are latex or wheat allergies. In a recent review, particular latex molecules  have been described to be major allergens in specific clinical phenotypes, such as in healthcare workers (Hev b 5 and Hev b 6), multi-operated patients (Hev b 11), subjects with spina bifida and patients with the so-called “latex –fruit syndrome” (Hev b 6). For example, several wheat proteins have been identified as causative allergens of occupational respiratory allergy  in bakery workers with wheat allergies (Tri a 14.). It is possible to test IgE reactivity in patients with different clinical profiles of wheat allergy (i.e., food allergy, wheat-dependent exercise-induced anaphylaxis, and baker’s asthma). In this regard, because immunotherapy could be attempted if allergen avoidance is not feasible, the aforementioned tool would allow a more precise diagnosis .