Susanne Glaumann

Peanut component Ara h 8 sensitization and tolerance to peanut

BACKGROUND Isolated Ara h 8 sensitization is suggested to be associated with no or mild symptoms among peanut-sensitized subjects. OBJECTIVE We sought to investigate the occurrence of systemic reactions in children with isolated sensitization to Ara h 8. METHODS Participants were 144 children sensitized to Ara h 8 (≥ 0.35 kU(A)/L) but not to Ara h 1, Ara h 2, or Ara h 3 (<0.35 kU(A)/L). An open oral challenge with peanut was performed in those subjects who did not consume peanut regularly, and an extended IgE reactivity profile was obtained. If the child had a documented history of systemic reactions up to grade I anaphylaxis, double-blind, placebo-controlled food challenges were performed. RESULTS One hundred twenty-nine (89.5%) children were either peanut consumers or did not react to peanut challenge. Another 14 (9.7%) children experienced oral cavity symptoms at the first 2 but not subsequent challenge doses. At the time of the double-blind, placebo-controlled food challenge, 1 boy with a previous mild systemic reaction to peanut experienced lip swelling, stomach cramping, and objective tiredness. Reanalysis of IgE levels showed an increase in peanut IgE levels from 1.5 to 8.8 kU(A)/L, but IgE levels to Ara h 8 remained stable and IgE levels to Ara h 1, Ara h 2, and Ara h 3 were all still less than 0.35 kU(A)/L. The IgE level to Ara h 6 was 0.45 kU(A)/L. CONCLUSION Isolated Ara h 8 sensitization indicates tolerance to peanuts in almost all cases. However, sensitization against thus far unidentified determinants in peanut might cause symptoms in rare cases.

Basophil allergen threshold sensitivity, CD‐sens, IgE‐sensitization and DBPCFC in peanut‐sensitized children

To cite this article: Glaumann S, Nopp A, Johansson SGO, Rudengren M, Borres MP, Nilsson C. Basophil allergen threshold sensitivity, CD‐sens, IgE‐sensitization and DBPCFC in peanut‐sensitized children. Allergy 2012; 67: 242–247.

The utility of peanut components in the diagnosis of IgE-mediated peanut allergy among distinct populations.

BACKGROUND Increasing data suggest that analysis of IgE to peanut components can be clinically helpful and possibly more accurate than IgE to whole peanut. Not all studies examining this topic, however, have used prospective samples, multiple components, and peanut challenges. OBJECTIVE We sought to determine the utility of peanut component testing, using a standardized, commercially available test done before oral peanut challenge in various populations of patients with suspected peanut allergy from 2 different countries. METHODS IgE to whole peanut and the recombinant allergen components Ara h 1, 2, 3, and 8 were analyzed from serum samples drawn before double-blind peanut challenge from 4 distinct cohorts of patients with suspected peanut allergy from 2 nations (United States and Sweden). RESULTS Patients (n = 167; median age, 11.7 years; interquartile range, 7.0-15.0 years) had serum analyzed for peanut components and completed an oral food challenge to peanut. Although IgE to peanut was the most sensitive test (0.93), Ara h 2 was the most specific (0.92) and provided the best positive predictive value (0.94) of all the tests. Ara h 2 was also the best overall diagnostic test by receiver operating characteristic analysis (area under the curve, 0.84; P < .05). CONCLUSIONS In patients with suspected peanut allergy, IgE to peanut is a sensitive test but is not specific. IgE to Ara h 2 is a more specific and more accurate diagnostic test in this sampling of patients with suspected peanut allergy. Given each tests attributes, a stepwise approach to testing may provide clinicians with a way to minimize the need for peanut challenges.

Oral Peanut Challenge Identifies an Allergy but the Peanut Allergen Threshold Sensitivity Is Not Reproducible

Background Double-blind placebo-controlled food challenge, DBPCFC, the gold standard for diagnosing food allergy, is time-consuming and potentially dangerous. A basophil allergen threshold sensitivity test, CD-sens, has shown promising results as a diagnostic tool in food allergy. Objectives To evaluate the reproducibility of oral peanut challenge and compare the outcome to CD-sens in peanut-sensitized children. Methods Twenty-seven children (4–19 years) underwent a DBPCFC followed by a single-blind oral food-challenge. The peanut challenges (1 mg to 5 g) were evaluated by severity scoring. Blood samples were drawn for CD-sens before the two first challenges. Results Thirteen children (48%) did not react at any of the challenges. Fourteen reacted at both peanut challenges but not to placebo. Only two of these children reacted at the same threshold dose and with the same severity score. All other children scored differently or reacted at different doses. For children with a positive challenge the geometric mean of the ratio of the doses was 1.834 (p = 0.307) and the arithmetic mean of the difference between the severity scores was 0.143 (p = 0.952). No association was obtained between the two peanut challenges regarding severity score (rs = 0.11, p = 0.71) or threshold dose (rs = 0.35, p = 0.22). Among the children positive in peanut challenge, 12 were positive in CD-sens. Two were low-responders and could not be evaluated. Geometric mean of the ratio of CD-sens values in children with a positive challenge was 1.035 (p = 0.505) but unlike for the severity score and the threshold dose the association between the two CD-sens values was strong (rs = 0.94, P<0.001). Conclusions For a positive/negative test the reproducibility is 100% for both peanut challenge and CD-sens. However, a comparison of the degree of allergen threshold sensitivity between the two tests is not possible since the threshold dose and severity scoring is not reproducible.

Anaphylaxis to peanut in a patient predominantly sensitized to Ara h 6.

Diagnosis of peanut allergy has improved thanks to component-resolved diagnostics. Peanut allergen component Ara h 2 is considered to indicate true peanut allergy. The component Ara h 6 is structurally similar to Ara h 2, but the diagnostic value of analyzing IgE antibodies to Ara h 6 is unclear. A boy sensitized (≥0.35 kUA/l) to Ara h 8 but not to Ara h 1, Ara h 2 and Ara h 3 was challenged with peanut and developed grade II anaphylaxis. In serum collected at the time of challenge a doubling of IgE to the peanut allergen extract was observed compared to allergy testing 9 months earlier. In contrast, IgE levels to Ara h 1, Ara h 2, Ara h 3 and to Ara h 8 were rather unchanged. After another 2 months, Ara h 6 was analyzed and revealed a level of 24 kUA/l whilst Ara h 2 was 0.12 kUA/l. We suggest that IgE sensitization to Ara h 6 caused the reaction and conclude that analyses of IgE levels to peanut and peanut components should be performed in connection with a challenge. Furthermore, levels to Ara h 2 below 0.35 kUA/l may still indicate a risk of severe reaction at the time of challenge since in rare cases, Ara h 6 IgE antibodies may be present without occurrence of IgE antibodies to Ara h 2.

Anaphylaxis to peanuts in a 16-year-old girl with birch pollen allergy and with monosensitization to Ara h 8

Anaphylaxis to peanuts in a 16-year-old girl with birch pollen allergy and with monosensitization to Ara h 8

Evaluation of basophil allergen threshold sensitivity (CD-sens) to peanut and Ara h 8 in children IgE-sensitized to Ara h 8

BackgroundDiagnosing peanut allergy properly is important and can be achieved by combining clinical history with various diagnostic methods such as IgE-antibody (IgE-ab) measurements, skin-prick test, basophil allergen threshold sensitivity (CD-sens) and food challenge. We aimed to evaluate CD-sens to peanut, Ara h 8 and Gly m 4 in relation to an oral peanut challenge in children IgE-sensitized to birch, peanut and Ara h 8 avoiding peanuts.MethodsTwenty children IgE-sensitized to birch pollen and Ara h 8, but not to Ara h 1, Ara h 2 or Ara h 3 were challenged orally with roasted peanuts. Blood samples were drawn for IgE-ab and CD-sens analysis. To measure CD-sens, basophils were stimulated in vitro with decreasing doses of allergens until threshold sensitivity was reached.ResultsAll children passed challenge without objective symptoms, but mild oral allergy syndrome (OAS) symptoms were reported in 6/20 children. Nineteen of twenty children were negative in CD-sens to peanut but 17/20 were positive to rAra h 8. Eleven of twenty children were positive in CD-sens to rGly m 4.ConclusionPositive CD-sens to rAra h 8 show that the Ara h 8 IgE-ab sensitized basophils can be activated by a rAra h 8 allergen and initiate an allergic inflammation despite a negative challenge. Hence, children sensitized to Ara h 8 but not to peanut storage proteins may be at risk for systemic allergic reaction when eating larger amounts of peanuts but most likely don’t have to fear smaller amounts.

IgG4 antibodies and peanut challenge outcome in children IgE-sensitized to peanut

1. Kawada T. Sleep in children with atopic dermatitis. Pediatr Allergy Immunol 2015: doi:10.1111/pai.12363. 2. Rolinck-Werninghaus C, Trentmann M, Reich A, Lehmann C, Staab D. Improved management of childhood atopic dermatitis after individually tailored nurse consultations: a pilot study. Pediatr Allergy Immunol 2015: doi:10.1111/pai.12338. 3. Lawson V, Lewis-Jones M, Finlay A, Reid P, Owens R. The family impact of childhood atopic dermatitis: the Dermatitis Family Impact questionnaire. Br J Dermatol 1998: 138: 107–13. 4. Moore K, David T, Murray C, Child F, Arkwright P. Effect of childhood eczema and asthma on parental sleep and wellbeing: a prospective comparative study. Br J Dermatol 2006: 154: 514–8.

Is molecular allergology cost-effective and cost saving in children with suspected peanut allergy compared to double blind placebo controlled food challenge (DBPCFC), open oral food challenge and skin prick test in Sweden?

Background Peanuts are one of the most common foods causing allergic reactions in children. IgE-ab sensitization to peanut has been reported in 7–11% of children in Western countries and the prevalence of peanut allergy (PA) in children varies between 0.75% and 3%. Given the PA impact on quality-of-life (QoL), accurate diagnosis is crucial because many sensitized individuals are actually tolerant to peanut. Peanut sensitization established by IgE antibodies (IgE-ab) in blood or skin prick test (SPT) often needs to be confirmed by the “gold standard” Doubleblind placebo-controlled food challenge (DBPCFC), a risky and expensive procedure. In clinical practice an open oral food challenge (OC) is performed instead of a DBPCFC. PA can be effectively diagnosed using molecular allergology (MA), identifying subjects at risk for PA reactions (IgE-ab to Ara h 1-2-3). No cost-effectiveness (CE) analyses are available on MA for allergy. Methods Three 5-year Markov models simulate the flow of 200 children PA suspected presenting to the general practitioner. The models compare different diagnostic approaches (DBPCFC, OC, SPT and MA), computing the cost-perQALY (Quality Adjusted Life Year) gained based on data from the literature. Calculations were performed for Sweden and BaseCase ® was used to present results. Care giver indirect costs are included in a sensitivity analysis. Results

Basophil allergen threshold sensitivity, and peanut allergen components in relation to DBPCFC in children with suspected peanut allergy

Methods DBPCFC was performed with increasing concentrations of peanut allergen (1 mg to 5 g of peanut) in 42 children with suspected IgE-mediated peanut-allergy. Blood samples were taken for analyses of CD-sens and quantification of IgE-antibodies to peanut and Ara h 1-3, 8-9. Basophils were stimulated in vitro with peanut allergen in descending doses until the threshold sensitivity was reached. CD-sens was defined on the basis of the allergen dose giving 50% of maximal basophil response, measured as expression of CD63. A positive challenge was defined as objective allergic symptoms.