Component-resolved diagnostics: laboratory results are not enough.

Allergic diseases, such as atopic eczema, food allergy, rhinitis and wheezing disorders are among the most fre­ quent complaints, especially in childhood. The current evidence also attests that type I allergic reactions are becoming more and more widespread, affecting up to 20% of the population. The World Health Organization (WHO) recently estimated that approximately 300 million people suffer from asthma worldwide [1], with a 10% average of European children suffering from this disor­ der. The global burden of asthma and – more gene rally – allergic diseases is impressive and well recognized, but still represents an open and unresolved challenge. The diagnosis of asthma and allergic disease is problem­ atic, particularly in preschool children, due to onset of poorly specific symptoms and because the conventional lung function tests cannot be carried out in early ages. Traditionally, the diagnosis of allergy has been based on medical history and clinical symptoms. The identifica­ tion of a new isotype of human immunoglobulin, called immunoglobulin E (IgE) [2], has however represented a milestone for improving our knowledge of the pathophysio­ logical mechanisms underlining this very particular type of inflammation, as well as for detection of allergic dia­ thesis, diagnosis and patient management. In particular, in vivo and in vitro tests for allergen­specific IgE (sIgE) play a key role for confirming a clinical suspicion and for choosing the most appropriate treatment. Until recently, the in vitro diagnostics of allergy was mainly based on detection of specific IgE (sIgE) against total extracts. However, allergen­extracts are heterogeneous in composi­ tion, since they contain a vast array of allergens, i.e., potent or dominant allergens, those present in modest amount or number, cross­reactive allergens of less impact and non­ allergenic components [3, 4]. The immunoassays for IgE antibody have undergone significant advancements in the last decades. In particular, the capacity to more pre­ cisely measure IgE antibodies in mass units and the total automation of assay systems have generated remarkable improvements of both analytical performances and diag­ nostic accuracy [5]. However, further and major devel­ opments are expected with the introduction of highly purified native or recombinant allergens, which would allow a more accurate identification of individual mole­ cules against which patients are sensitized. Assays based on recombinant and/or highly purified allergens allow a deeper examination of cross­reactions, risk molecules and prognostic significant sensitizations, thus paving the way to the so­called “molecular or component­resolved diag­ nostics (CRD)” [6]. CRD more suitably allows the genuine sensitization of patients toward a given allergenic source to be identified, along with cross­reactive molecules that suggest cross­sensitization to several allergen sources [7]. For routine laboratory testing, the molecular approach should be performed using two different tools, i.e., the tra­ ditional measurement of an individual specific IgE anti­ body, and/or multiplex multiarrays that can simultaneous screen a large number of specificities for the same aller­ gen and for different related or significant allergens [8]. The new analytical method ImmunoCAPTMISAC microarray (ThermoFisher Immunodiagnostics, Uppsala, Sweden) has recently been introduced to the market. This system allows to test as many as 112 recombinant or purified aller­ gen components, from 52 sources, in a single analytical step [9]. An article about the evaluation of this new micro­ array and the comparison of its analytical performance with that of conventional ImmunoCAP assay has been previously published in Clinical Chemistry and Laboratory Medicine [10]. In this issue of the journal, the article of Villalta and colleagues [11] reports and discusses an unexpected and isolated IgE reactivity to nJug r 2 (native walnut vicilin), which has been detected by ImmunoCAP ISACTM. This finding is frequently related to cross­reactive carbohydrate epitopes and lacks clinical significance. So, the value of the study relays in the authentication that technological developments do not necessarily translate in clinical improvements, and that further efforts should be placed to correctly assess and interpret test results. This is particularly true in the field of allergy testing, as confirmed by a recent survey performed in Italy which supported previous data demonstrating that general prac­ titioners are not confident with request for and interpreta­ tion of laboratory data. The survey also emphasized that