Ara h 2 is the dominant peanut allergen despite similarities with Ara h 6 https://doi.org/10.1016/j.jaci.2020.03.026 Abstract Background Ara h 2 specific-IgE (sIgE) is to date the best serologic marker to diagnose peanut allergy. Ara h 6 shares ~60% sequence identity and multiple epitopes with Ara h 2. Objectiv To assess the diagnostic utility and relative importance of Ara h 2 and Ara h 6 in peanut allergy. Methods A cohort (n=100) of peanut allergic (PA), peanut sensitized but tolerant (PS) and non-sensitized non-allergic (NA) children were studied. sIgE levels to peanut and individual allergens were quantified using ImmunoCAP. ImmunoCAP inhibition experiments and mast-cell activation tests (MAT) were performed to both Ara h 2 and Ara h 6. Statistical analyses were performed using SPSS v14 and Prism v7. Results Ara h 2-sIgE and Ara h 6-sIgE showed the greatest diagnostic accuracy for peanut allergy compared with sIgE to peanut and other peanut allergens. Most PA patients were sensitized to both Ara h 2 and Ara h 6. Ara h 2 reduced Ara h 2-sIgE binding more than Ara h 6 (p<0.001) whereas Ara h 6-sIgE binding was inhibited to a similar degree by Ara h 2 and Ara h 6 (p=0.432). On the MAT, Ara h 2 induced significantly greater maximal reactivity (p=0.001) and lower EC50 (p=0.002) than Ara h 6 when testing co-sensitized individuals. Conclusions Ara h 2-sIgE and Ara h 6-sIgE provide the greatest accuracy for diagnosis peanut allergy. Ara h 2 is the dominant conglutin in peanut allergy in the UK, despite a degree of cross-reactivity with Ara h 6. All authors: OliverHemmings GeorgeDu ToitFRCPCH SuzanaRadulovic GideonLack FRCPCH Alexandra F.Santos