Pfiffner P, Stadler BM, Rasi C, et al. Cross-reactions vs co-sensitization evaluated by in silico motifs and in vitro IgE microarray testing
ABSTRACT Using an in silico allergen clustering method, we have recently shown that allergen extracts are highly cross-reactive. Here we used serological data from a multi-array IgE test based on recombinant or highly purified natural allergens to evaluate whether co-reactions are true cross-reactions or co-sensitizations by allergens with the same motifs.
The serum database consisted of 3142 samples, each tested against 103 highly purified natural or recombinant allergens. Cross-reactivity was predicted by an iterative motif-finding algorithm through sequence motifs identified in 2708 known allergens.
Allergen proteins containing the same motifs cross-reacted as predicted. However, proteins with identical motifs revealed a hierarchy in the degree of cross-reaction: The more frequent an allergen was positive in the allergic population, the less frequently it was cross-reacting and vice versa. Co-sensitization was analyzed by splitting the dataset into patient groups that were most likely sensitized through geographical occurrence of allergens. Interestingly, most co-reactions are cross-reactions but not co-sensitizations.
The observed hierarchy of cross-reactivity may play an important role for the future management of allergic diseases.
- SourceAvailable from: Ignacio J Dávila
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- "They used the term “co-sensitization” to describe multiple, unrelated sensitizations to several structurally unrelated allergen groups. The structural basis of cross-reactivity was recently confirmed by Pfiffner et al.  in a micro-array study; 3,143 serum samples were tested to see whether they contained IgE that bound to any of 103 highly purified natural or recombinant allergens immobilized on the array. The researchers confirmed the previous cross-reactivity data from conventional IgE assays and reported predictions of cross-reactivity based on an iterative, motif detection algorithm. "
ABSTRACT: The type of allergic sensitization is of central importance in the diagnosis and treatment of respiratory allergic diseases. At least 10% of the general population (and more than 50% of patients consulting for respiratory allergies) are polysensitized. Here, we review the recent literature on (i) the concepts of polysensitization, paucisensitization, co-sensitization, co-recognition, cross-reactivity, cross-sensitization, and polyallergy, (ii) the prevalence of polysensitization and (iii) the relationships between sensitization status, disease severity and treatment strategies. In molecular terms, clinical polysensitization can be divided into cross-sensitization (also known as cross-reactivity, in which the same IgE molecule binds to several allergens with common structural features) and co-sensitization (the simultaneous presence of different IgEs binding to allergens that may not necessarily have common structural features). There is a strong overall association between sensitization in skin prick tests and total IgE values but there is debate as to whether IgE thresholds are useful guides to the presence or absence of clinical symptoms in individual cases. Molecular information from component-resolved techniques appears to be of value for diagnosis and treatment decisions. Polysensitization develops over time and is a risk factor for respiratory allergy (being associated with disease severity) and therefore has clinical relevance for treatment decisions. The subterm polysensitization has been defined as polysensitization to between two and four allergens. Polyallergy is defined as clinically confirmed allergy to two or more allergens. Single-allergen grass pollen allergen immunotherapy (AIT) is safe and effective in polysensitized patients, whereas multi-allergen AIT requires more supporting evidence. Given that AIT may be more efficacious in moderate-to-severe disease than in mild disease, polysensitization could be an indication for this type of treatment. There is a need for flowcharts or decision trees for choosing the allergens for AIT in polysensitized patients and polyallergic patients.05/2014; 4(1):16. DOI:10.1186/2045-7022-4-16
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ABSTRACT: To evaluate the relevance of results obtained using allergen microarray technique for the description of the IgE repertoire in allergic patients. Allergen microarray was introduced at the beginning of the last decade. Since then, an increasing number of allergens have been identified, correspondingly increasing the accuracy of the description of immunoglobulin (Ig)E repertoire. In the last 2 years, a large number of articles were published that accurately described not only the general features of this technique, but also the use of allergen microarray in specific situations. The recent availability of highly purified or recombinant allergen components has deeply modified the laboratory approach to allergy diagnosis that, now, it cannot be limited to the detection of IgE specific to extractive allergens. Indeed, these contain both specific components (i.e. molecules strictly associated to that allergen source) and pan-allergen or cross-reacting allergens (i.e. molecules that are present in different similar allergen sources or that are present in highly homologous structures in different species). Newer techniques such as recombinant allergen testing and allergen microarray allow a more detailed evaluation of IgE responses. Future research is needed to more clearly define their role in clinical practice.Current Opinion in Allergy and Clinical Immunology 05/2012; 12(4):434-9. DOI:10.1097/ACI.0b013e32835535b8 · 3.66 Impact Factor
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ABSTRACT: Among the peach-derived allergens which are already known, the lipid transfer protein (Pru p 3) seems to be the one to exert severe allergic reactions. To identify and characterize a new peach allergen causing a clinical picture similar to that of Pru p 3. Patients were selected on the basis of their severe clinical reactivity and negative results to a panel of peach allergens available on the ISAC103 microarray. Several in-house and commercial preparations were compared. Several methods were used to characterize the newly identified molecule. Specific IgE and inhibition assays were performed using the Allergen micro-Beads Array (ABA) assay. Negative ISAC results to Pru p 3 were confirmed by additional testing in contrast with the positive results obtained by commercial Pru p 3-enriched peach peel extracts. The analyses of one of these preparations led to the identification of Peamaclein, a new allergenic protein. It is a small, basic, cysteine-rich, heat-stable, digestion-resistant protein, homologous to a potato antimicrobial peptide. Peamaclein was able to trigger positive skin test reactions and to bind IgE in the ABA assay. It displays an electrophoretic mobility and chromatographic behaviour similar to that of Pru p 3; therefore, it can be hidden in Pru p 3 preparations. In fact, Pru p 3-enriched peach peel extracts were found to contain both Pru p 3 and Peamaclein by means of comparative in vivo testing, and by biochemical and immunochemical assays. Commercially available anti-Pru p 3 polyclonal antibodies were found to have a double specificity for the two molecules. A new allergen from peach belonging to a new family of allergenic proteins has been identified and characterized. This knowledge on Peamaclein will improve our understanding on the clinical aspects of the peach allergy and the quality of diagnostic reagents.Clinical & Experimental Allergy 01/2013; 43(1):128-40. DOI:10.1111/cea.12028 · 4.32 Impact Factor