23
Jan.
2012
Journal: The Journal of Allergy and Clinical Immunology
Author: Moisés A. Calderón, Linda Cox, Thomas B. Casale, Philippe Moingeon, Pascal Demoly
Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: Looking at the published evidence
In allergen immunotherapy there is debate as to whether polysensitized patients are best treated with many allergens simultaneously (chosen according to the sensitization profile, a predominantly North American approach) or a single allergen (chosen according to the most clinically problematic allergy, a predominantly European approach). In patients seeking treatment for moderate-to-severe respiratory allergies, polysensitization is more prevalent (range, 50% to 80%) than monosensitization in both the United States and Europe. Safe, effective, single-allergen preparations will most likely have been tested in polysensitized patients. In robust, large-scale clinical trials of grass pollen sublingual tablets, polysensitized patients benefited at least as much from allergen immunotherapy as monosensitized patients. A recent review of multiallergen immunotherapy concluded that simultaneous delivery of multiple unrelated allergens can be clinically effective but that there was a need for additional investigation of therapy with more than 2 allergen extracts (particularly in sublingual allergen immunotherapy). More work is also required to determine whether single-allergen and multiallergen immunotherapy protocols elicit distinct immune responses in monosensitized and polysensitized patients. Sublingual and subcutaneous multiallergen immunotherapy in polysensitized patients requires more supporting data to validate its efficacy in practice.
16
Jan.
2012
Journal: Allergy
Author: R. I. Monsalve, A. Vega, L. Marqués, A. Miranda, J. Fernández, V. Soriano, S. Cruz, C. Domínguez-Noche, L. Sánchez-Morillas, M. Armisen-Gil, R. Guspí, D. Barber
Component-resolved diagnosis of vespid venom-allergic individuals: phospholipases and antigen 5s are necessary to identify Vespula or Polistes sensitization
Background: Cross-reactivity between hymenoptera species varies according to the different allergenic components of the venom. The true source of sensitization must therefore be established to ensure the efficacy of venom immunotherapy.
Objective: In the Mediterranean region, Polistes dominulus and Vespula spp. are clinically relevant cohabitating wasps. A panel of major vespid venom allergens was used to investigate whether serum-specific IgE (sIgE) could be used to distinguish sensitization to either vespid.
Methods: Fifty-nine individuals with allergic reactions to vespid stings and positive ImmunoCAP and/or intradermal tests to vespid venoms were studied. sIgE against recombinant and natural venom components from each wasp species was determined using the ADVIA Centaur® system.
Results: sIgE against recombinant antigen 5s sensitization to be detected in 52% of the patients tested (13/25). The sensitivity increased to 80% (20/25), when using natural antigen 5s, and to 100% with the complete panel of purified natural components, because the sIgE was positive to either the antigen 5s (Pol d 5/Ves v 5) or to the phospholipases (Pol d 1/Ves v 1) of the two vespids, or to both components at the same time. In 69% of cases, it was possible to define the most probable sensitizing insect, and in the rest, possible double sensitization could not be excluded. Vespula hyaluronidase was shown to have no additional value as regards the specificity of the assay.
Conclusions: The major allergens of P. dominulus’ and Vespula vulgaris’ venom, namely phoshpholipases and antigen 5s, are required to discriminate the probable sensitizing species in vespid-allergic patients.
16
Jan.
2012
Journal: Allergy
Author: K. Gerhold, A. Avagyan, E. Reichert, C. Seib, D. V. Van, E. O. Luger, A. Hutloff, E. Hamelmann
Prenatal allergen exposures prevent allergen-induced sensitization and airway inflammation in young mice
Background: Immune-modulation such as tolerance induction appears to be an upcoming concept to prevent development of atopic diseases. Pregnancy might present a critical period for preventing allergic sensitization of the progeny. We investigated the effect of maternal allergen exposures during pregnancy on allergen-induced sensitization and airway inflammation in the offspring in a murine model.
Methods: BALB/c mice were exposed to aerosolized ovalbumin (OVA) three times per week from day 7 of pregnancy until delivery (day 0). Offspring were systemically sensitized by six intraperitoneal injections with OVA between postnatal days 21 and 35, prior to airway allergen challenges on days 48, 49, and 50. Analyses were performed on day 52. To examine long-lasting effects of maternal OVA exposures some offspring were sensitized between days 115 and 129; analyses took place on day 147.
Results: Compared to maternal placebo exposures, maternal OVA exposures suppressed OVA-specific IgE serum levels and inhibited development of allergen-induced airway inflammation in the OVA-sensitized offspring on both days 52 and 147. This protective effect was associated with a shift from a predominant Th2 immune response toward a predominant production of the cytokines IFN-γ and IL-10. Further, maternal OVA exposures were associated with development of CD25+Foxp3+ regulatory T cells (Tregs) in the OVA-sensitized offspring. Depletion of Tregs or neutralization of IL-10 prior to allergen sensitization re-established OVA-induced sensitization and eosinophilic airway inflammation in the OVA-sensitized offspring.
Conclusions: In our model, maternal allergen exposures during pregnancy prevented later allergen-mediated sensitization and airway inflammation by allergen-specific tolerance induction in the offspring.
04
Jan.
2012
Journal: The Journal of Allergy and Clinical Immunology
Author: Salvatore Tripodi, Tullio Frediani, Sandra Lucarelli, Francesco Macrì, Giuseppe Pingitore, Andrea Di Rienzo Businco, Arianna Dondi, Paola Pansa, Giovanni Ragusa, Riccardo Asero, Diego Faggian, Mario Plebani, Paolo Maria Matricardi
Molecular profiles of IgE to Phleum pratense in children with grass pollen allergy: Implications for specific immunotherapy
Background
The so-called component-resolved immunotherapy of allergies proposes an immunization tailored to the molecular sensitization profiles of individual patients.
Objectives
We sought (1) to investigate the profiles of IgE sensitization to Phleum pratense in children with grass pollen allergy and (2) to define the compatibility of these profiles with a mixture of recombinant allergenic molecules of P pratense previously proposed for specific immunotherapy.
Methods
We examined 200 children (age, 4-18 years; 126 boys) with allergic rhinitis, asthma, or both ascertained through validated questionnaires. Each child underwent skin prick testing (ALK-Abelló) and serum IgE assays (ImmunoCAP, Phadia) with 9 pollen extracts. Sera reacting against P pratense were tested for the individual molecules (rPhl p 1, rPhl p 2, rPhl p 4, nPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11, and Phl p 12). Through a combinatorial approach, the IgE individual sensitization profiles were matched against an experimental allergen-specific immunotherapy (SIT) preparation containing Phl p 1, Phl p 2, Phl p 5, and Phl p 6.
Results
Among the 176 of 200 children with IgE sensitization to P pratense extract, 39 profiles of sensitization to the 8 allergenic molecules tested (cutoff, 0.35 kU/L) were identified. This high heterogeneity was reduced by considering only 6 or 4 P pratense molecules but not by increasing the cutoff levels of IgE positivity. The molecular profile of the experimental SIT preparation matched that of 7 (4%) of 176 patients only; the remaining 169 patients were classified in 4 mismatch categories: underpowered (29%), overpowered (32%), underpowered/overpowered (32%), and unrelated (3%).
Conclusions
IgE sensitization profiles to P pratense are highly heterogeneous. Molecularly designed SIT preparations tailored to patients’ needs should consider this high heterogeneity and be driven by locally performed population studies.
23
Dec.
2011
Journal: Pediatric Allergy and Immunology
Author: Simona E. K. Žitnik, Tina Vesel, Tadej Avčin, Mira Šilar, Mitja Košnik, Peter Korošec
Monitoring honeybee venom immunotherapy in children with the basophil activation test
Abstract
Background: New in vitro methods are essential for developing better follow-up criteria for venom immunotherapy (VIT).
Methods: Thirty-one children with a history of honeybee venom–induced systemic anaphylaxis were included in this prospective, single-blinded study. The basophil CD63 activation test (BAT) was assessed before starting VIT, at the end of the build-up phase (day 5), 6 months later, and after 2–4 yr of VIT.
Results: Basophil CD63 activation test allowed identification of the culprit insect in 74% of honeybee venom–allergic children. In comparison, IgE reactivity was single positive in only 52% of children. Five days after starting VIT, BAT was highly comparable to before VIT. However, after 6 months and further after 2–4 yr of VIT, a significant and approximately fourfold decrease was demonstrated in CD63 response at sub-maximal 0.1 μg/ml allergen concentration, which mainly represents cellular sensitivity. No such differences were found at a higher 1 μg/ml of allergen concentration. Person-to-person analyses showed that after 2–4 yr of VIT, a marked CD63 decrease was evident in 85% of children. In addition, elevated basophil sensitivity measured before VIT was associated with the appearance of side effects observed during the build-up phase of VIT.
Conclusion: Basophil CD63 allergen–specific sensitivity seems to be a promising tool for monitoring protective immune response in honeybee VIT.