Acknowledgments
We thank Tomas Barker-Tejeda for the critical reading of the manuscript.
Figure Legends
Figure 1: Diagnostic algorithm and decision tree for AIT using CRD in Grass pollen allergy. Grass pollen allergy is one of the most studied allergy models. Major allergen sensitization is required before considering AIT. The combination of major allergens and pan-allergens provides the necessary tools for AIT decisions. Profilin allergy, might be a contraindication only in severe food allergic patients, while double sensitization to both pan-allergens is associated to many years of disease evolution, poly-sensitization and poor intervention outcome
Figure 2: Diagnostic algorithm and decision tree for AIT using CRD in Olive pollen allergy. Olive pollen allergies is one of the most complex allergy models. Usually olive cultivars cover homogeneous areas and present acute differences in allergen pollen content. In dense pollen areas, patients are exposed to the highest pollen counts recorded. Th existing of complex profiles, marked by minor allergens sensitization, makes CRD a fundamental tool for patient management and AIT decissions.
Figure 3: Diagnostic algorithm and decision tree for AIT using CRD in nsLTPs mediated allergies. The existence of cross-reactivity between nsLPTs from Artemisia and Platanus pollens, makes CRD necessary. LTP immunotherapy with an enriched Pru p 3 can be considered in Countries with availability of this type of therapy
Figure 4: Diagnostic algorithm for in vitro diagnostics and Decision tree for AIT using CRD in pollen allergies. Discrimination of primary sensitizers and pan-allergens positivity is needed. AIT guidelines do not recommend AIT for poly-sensitized patients
Figure 5: Diagnostic algorithm for in vitro diagnostics in epithelia allergy and associated decision tree for AIT using CRD. The proposed algorithm discriminates between primary sensitization and cross-reactive sIgE response. Only patients sensitized to major allergens should be eligible for AIT.
Figure 6: Established discriminating and cross-reactive allergens of HBV, YJV and PDV. While allergens are identified that enable a differentiation between HBV (Api m 1, Api m 3, Api m 4 and Api m 10) and YJV/PDV (Ves v 1/Pold 1 and Ves v 5/Pol d 5) sensitization, the so far known allergens of YJV and PDV exhibit cross-reactivity.
Figure 7: Diagnostic algorithm for in vitro diagnostics of (A) HBV and YJV allergy and (B) YJV and PDV allergy. The diagnostic algorithm shown in (A), with the corresponding PDV allergens Pol d 1 and Pol d 5 can also be used to discriminate between HBV and PDV allergy. In addition, to discriminate in the case of double-positive test results, CRD might also be useful in cases of negative results despite a convincing history of venom allergy or in cases of discrepancies between history, skin tests and venom extract-based testing. A plus indicates a positive and a minus a negative test result. Of note, the allergens Api m 4 and Pol d 1 (in brackets) are only available for selected multiplex sIgE test platforms. *The allergens Api m 2 and Api m 5 are potentially cross-reactive with their homologues from YJV and PDV (not available for CRD) and, hence, a positive test results does not necessarily exclude allergy to vespid venom.
Figure 8: Diagnostic algorithm for in vitro diagnostics in peanut allergy oriented to make POIT decision. Discriminant analysis between storage allergens and cross-reactive to pollen and nsLTPs is proposed. Only patients with positive sIgE to any of the Ara h 1,2,3,6 should be eligible for POIT.
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Table 1: Characteristics and significance of pollen, vegetables, mites and epithelia allergens available for CRD and relevant for AIT decisions