Ara h 2 and Ara 6 are the best predictors of severe peanut allergy: a double‐blind placebo‐controlled study

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Component‐resolved diagnostics offers a modern tool in peanut allergy, but studies applying consistently double‐blind placebo‐controlled challenges are lacking. We aimed to optimize diagnostics for moderate‐to‐severe peanut allergy in a birch‐endemic region and to create an oral‐peanut challenge with its allergen activity characterized.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We performed double‐blind placebo‐controlled peanut challenges for a referred sample of 6‐ to 18‐year‐olds with peanut sensitization or a high suspicion of peanut allergy, including anaphylaxis. We measured specific IgE (<jats:styled-content style="fixed-case">sIgE</jats:styled-content>) to Ara h 1, 2, 3, 6, 8, and 9. Testing of allergen activity of the challenge products was by IgE microarray inhibition.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Of the 102 patients, 69 were challenge positive: 25 (36%) had severe, 36 (52%) moderate, and 8 (12%) mild symptoms; 38 (37%) received adrenalin. <jats:styled-content style="fixed-case">SI</jats:styled-content>gE to Ara h 6 <jats:styled-content style="fixed-case">AUC</jats:styled-content> 0.98 (95%<jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.96–1.00) was the best marker of moderate‐to‐severe allergy. When <jats:styled-content style="fixed-case">sIgE</jats:styled-content> to Ara h 2 and Ara h 6 was measured together, all (100%) severe reactions at low doses were successfully diagnosable. <jats:styled-content style="fixed-case">SI</jats:styled-content>gE to Ara h 8 had no diagnostic value, <jats:styled-content style="fixed-case">AUC</jats:styled-content> 0.42 (95%<jats:styled-content style="fixed-case">CI</jats:styled-content>, 0.30–0.52). Both nonroasted and roasted peanut inhibited 100% of IgE binding to Ara h 1, 2, 3, and 6. Nonroasted peanut inhibited 87% of IgE binding to Ara h 8, roasted inhibited 30%. The products lacked Ara h 9 activity.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Co‐sensitization to Ara h 2 and Ara h 6 was associated with severe reactions distinguishing severe allergy from mild symptoms. <jats:styled-content style="fixed-case">SI</jats:styled-content>gE to Ara h 8 added no diagnostic value. Component‐resolved diagnostics reduce the need for oral challenges in peanut allergy.</jats:p></jats:sec>