Annebeth E. Flinterman

Acute allergic reactions in children with AEDS after prolonged cow's milk elimination diets

Background:  Food allergy is not always correctly diagnosed in children with atopic eczema dermatitis syndrome (AEDS) and treatment with an avoidance diet is not without danger.

Peanut epitopes for IgE and IgG4 in peanut-sensitized children in relation to severity of peanut allergy

BACKGROUND Better understanding of the relationship between antibody response to peanut and clinical sensitivity might lead to more accurate prognostication. OBJECTIVE We sought to investigate peanut-specific IgE and IgG4 epitope diversity in relation to challenge-defined clinical sensitivity to peanut in a group of peanut-sensitized children. METHODS Clinical sensitivity was determined by means of double-blind, placebo-controlled peanut challenges in 24 sensitized children. Six atopic control subjects were included. Specific IgE and IgG4 binding to 419 overlapping 15-amino-acid peptides representing the sequence of recombinant Ara h 1, Ara h 2, and Ara h3 was analyzed by means of microarray immunoassay. RESULTS Peanut-sensitized patient sera bound significantly more IgE and IgG4 epitopes than control sera. This patient group reacted to the same Ara h 1, Ara h 2, and Ara h 3 epitopes as reported previously. There was a positive correlation between IgE epitope diversity (ie, number of epitopes recognized) and clinical sensitivity (r = 0.6), such that patients with the greatest epitope diversity were significantly more sensitive than those with the lowest diversity (P = .021). No specific epitopes were associated with severe reactions to peanut. IgG4 binding was observed to largely similar epitopes but was less pronounced than IgE binding and did not relate to the clinical sensitivity to peanut. IgE and IgG4 epitope-recognition patterns were largely stable over a 20-month period. CONCLUSION Clinical sensitivity, as determined by means of double-blind, placebo-controlled peanut challenge, is positively related to a more polyclonal IgE response, which remains stable over time.

Children with peanut allergy recognize predominantly Ara h2 and Ara h6, which remains stable over time

Background In peanut‐allergic adults, IgE is mainly directed to Ara h1 and Ara h2. More recently, a role for Ara h6 has been suggested. In contrast to adults, IgE in children can fluctuate over time. Therefore, children may have a more dynamic reactivity to peanut.

Hazelnut allergy: from pollen-associated mild allergy to severe anaphylactic reactions

Purpose of reviewHazelnut allergy can vary between mild oral symptoms and potentially dangerous anaphylaxis. There is a need to predict which subjects are at risk for severe reactions. In this study, possibilities for ‘component-resolved diagnosis’, based on sensitization to different allergens in hazelnut, are discussed. Recent findingsOne type of hazelnut allergy can be associated with sensitization to homologues of pollen allergens, predominantly birch, in hazelnut: Cor a 1 (Bet v 1) and Cor a 2 (profilin). These allergens account for relatively mild symptoms. However, subjects can also be sensitized to several other allergens in hazelnut that are related to more severe symptoms. These allergens are homologues of allergens in other nuts and peanut: Cor a 8 (lipid transfer protein) and Cor a 9 (11S globulin) and perhaps Cor a 11 (7S globulin). The clinical relevance of these and other potential hazelnut allergens has to be further defined. The diagnosis of hazelnut has to be confirmed by oral double-blind placebo-controlled food challenge. SummarySensitization to hazelnut can either be associated with mild oral symptoms, depending on sensitization to pollen, or with more serious allergic symptoms, related to sensitization to homologues of nut and peanut allergens.

Probiotics Have a Different Immunomodulatory Potential in vitro versus ex vivo upon Oral Administration in Children with Food Allergy

Background: Previous studies suggest that administration of probiotics in vitro can stimulate regulatory and Th1 immune responses. We studied both the in vitro immunological effects of probiotics and the ex vivo immunological effects after oral administration of probiotics in children with food allergy, a Th2-mediated disease. Methods: Thirteen children were enrolled. Probiotics (n = 7) or placebo (n = 6) were orally administered during 3 months. At baseline and after 1 and 3 months, peripheral blood mononuclear cells were stimulated with crude peanut extract, anti-CD3, or anti-CD40 and IL-4 in the presence (in vitro response) or absence (ex vivo response) of probiotics. The proliferation and production of IFN-γ, IL-5, IL-13, IL-10, TNF-α, IL-6 and IgE were analyzed. Sensitization to peanut, cow’s milk and hen’s egg was determined before and after treatment. Results: The in vitro addition of probiotics to peripheral blood mononuclear cell cultures resulted in enhanced proliferation and production of IFN-γ, IL-10 and TNF-α. After oral treatment, proliferation in the presence of probiotics increased, whereas in vitro IgE production decreased in the probiotics group compared to baseline. The ex vivo production of IL-10, TNF-α and IL-6 tended to decrease. Th1 and Th2 cytokines were not altered. Sensitization remained unchanged. Conclusion: Probiotics enhanced the production of Th1 and regulatory cytokines in vitro. Oral administration of probiotics resulted in a slightly decreased ex vivo production of IL-10, TNF-α and IL-6. This indicates that probiotics have a different potential to modulate the immune response in vitro versus ex vivo.

T cell responses to major peanut allergens in children with and without peanut allergy

Background T cell responses involved in peanut allergy are poorly understood.

Parental anxiety before and after food challenges in children with suspected peanut and hazelnut allergy

Zijlstra WT, Flinterman AE, Soeters L, Knulst AC, Sinnema G, L’Hoir MP, Pasmans SG. Parental anxiety before and after food challenges in children with suspected peanut and hazelnut allergy.
Pediatr Allergy Immunol 2010: 21: e439–e445.
© 2009 John Wiley & Sons A/S

Diagnostic value of hazelnut allergy tests including rCor a 1 spiking in double-blind challenged children

The diagnostic value of hazelnut allergy tests in double‐blind challenged children is largely unknown. The aim of this study was to analyze the performance of current diagnostic tests for hazelnut allergy in children and the effect of spiking.

The level of specific IgE is a moderate predictor for the outcome of a double-blind placebo-controlled food challenge for hazelnut in children

Literature about the value of diagnostic tests for hazelnut allergy in children is scarce. For peanut allergy cutoff levels of specific IgE with a 95% positive predictive value (PPV) were published. To evaluate current diagnostics for hazelnut allergy in children, data of 151 children, who underwent a double-blind placebo-controlled food challenge (DBPCFC) for hazelnut were analyzed. The PPV or negative predictive value (NPV) of the level of specific IgE (CAP) for hazelnut and the size of the skin prick test (SPT) for hazelnut was determined. The influence of spiking of the CAP for hazelnut with rCor a 1 was analyzed. The level of specific IgE for hazelnut was a moderate predictor for a positive DBPCFC for hazelnut. No cutoff levels of specific IgE for hazelnut with a 95% PPV could be determined. Before Cor a 1 spiking the maximum reached PPV was 73% for a cutoff level of 26 kUA/L, after spiking the maximum reached PPV was 64% for a cutoff level of 31 kUA/L. The spiking increased the NPV from 91% to 100% for a cutoff level of 0.35 kUA/L. SPT was a better predictor for a positive DBPCFC compared to the level of specific IgE. When the SPT >16 mm, the PPV was 100%. By combining both tests, the PPV reached 100% when the level of specific IgE for hazelnut was >5 kUA/L and the level of SPT was >12mm. However, the PPV of 100% for SPT alone and the combination of CAP and SPT accounted for only 11% respectively 13% of the children undergoing a DBPCFC for hazelnut. So, the level of specific IgE and reactivity of SPT are moderate predictors for the outcome of a DBPCFC for hazelnut in children. New diagnostic tools are needed to replace the DBPCFC which is burdensome, expensive and limited available.