Pfiffner P, Stadler BM, Rasi C, et al. Cross-reactions vs co-sensitization evaluated by in silico motifs and in vitro IgE microarray testing

University Institute of Immunology, University of Bern, Switzerland.
Allergy (Impact Factor: 6.03). 11/2011; 67(2):210-6. DOI: 10.1111/j.1398-9995.2011.02743.x
Source: PubMed


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.

7 Reads
  • Source
    • "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. [16] 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. "
    [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    ABSTRACT: The specific allergy diagnosis is based on: anamnesis, skin prick test, in vitro diagnostic and provocation test. There is no doubt that the measurement of specific IgE antibodies (slgE) in sera is the most important and also practical available in vitro-test. The detection and quantification of IgE - the same is true for the skin prick test - indicate a specific sensitization against the relevant allergen. The significance of the allergy diagnostic depends on the quality of the allergen extract used and also on the different methods. Used antigens and allergens have to be characterized and standardized (major and marker allergens). The importance of recombinant allergens is increasing. The exclusive measurement of total IgE for the allergy diagnostic is not reasonable because no allergen specific conclusion is possible, but gives additional information concerning the interpretation of allergen-specific IgE in patient's sera. The production of allergen specific IgG-antibo-dies is part of the normal immune response to a xenobiotic exposure; there is no correlation between clinical symptoms of immediate type hypersensitivity reactions and specific IgG-antibo-dies. Antigen-specific IgG is an important tool in the diagnosis of hypersensitivity pneumonitis. Cellular test systems are methodologically complex, expensive, normally poorly dedicated for the sample transport and sophisticated in performance and interpretation. They are complementary tools for a specific in vitro-allergy diagnostic with a clinical indication and under controlled procedures. Standard protocols including round robin tests and quality controls for each of these in vitro-tests are highly recommended.
    Tagliche Praxis 55(2):233-245.
  • [Show abstract] [Hide abstract]
    ABSTRACT: We present a case of anaphylactic shock induced by celery ingestion in a 28-year old woman with pollinosis during allergen (50% birch, 50% grass) immunotherapy. A female patient, aged 28 was admitted to the clinic due to a serious anaphylactic reaction. The event took place 15 min after ingesting fresh celery. She recovered after routine treatment with adrenaline, corticosteroids and antazoline. Our case shows the possibility of simultaneous occurrence of hypersensitivity to inhaled allergens and food. In such cases, it is considered part of cross-reactivity We discuss the importance of cross- reactivity associated with sensitization to pollen and vegetable foods.
    Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine) 01/2012; 66:132-4. DOI:10.5604/17322693.986123 · 0.57 Impact Factor
Show more