Variable IgE Cross-Reactivity Between Peanut 2S-Albumins: The Case for Measuring IgE to Both Ara h 2 and Ara h 6

To quantify the IgE cross-reactivity between Ara h 2 and Ara h 6. Allergic antibodies to these potent 2S-albumin proteins are good predictors of clinical reactivity to peanut. Because of structural homologies, Ara h 6 is generally considered to cross-react extensively with Ara h 2; therefore questioning the usefulness of testing both 2S-albumins for diagnosis of peanut allergy. However, there are reports of peanut allergic patients only sensitized to Ara h 6 or highly variable ratios between Ara h 2 and Ara h 6, suggesting that cross-reactivity between these peanut 2S-albumin proteins was not as consistent as previously theorized.

Sera was collected from 20 French peanut-allergic children and 12 US peanut-allergic children with a strong history of peanut-induced allergic reactions.

Peanut 2S-albumins were purified from raw peanuts. Cross-reactivity between Ara h 2 and Ara h 6 was quantified using two different approaches: solid-phase coated allergens and competitive fluid-phase assay. Sera reactivity was measured using the residual IgE binding to one 2S-albumin after depletion of IgE antibodies recognizing the other 2S-albumin. Cross-reactivity was further evaluated by competitive inhibition of IgE-binding and by a model of mast cell degranulation.

The authors found highly variable levels of IgE cross-reactivity among the patients’ sera. Depletion of Ara h 6 induced a mean decrease of IgE-binding to Ara h 2 of 24% indicating that about 76% of IgE binding to Ara h 2 was mediated by non-cross-reactive proteins. Depletion of Ara h 2 specific antibodies induced a higher mean decrease of IgE-binding to Ara h 6 of 46%. The mean cross-reactive antibodies represented only 17.1% of 2S albumins. The higher level of Ara h 2 specific IgE was due to IgE binding capacity of an insertion containing the repeated immunodominant linear epitope DPYSP^OHS. The authors investigated cross-reactivity between the 2S-albumins with a competitive fluid-phase assay which confirmed that IgE reactivity of Ara h 2 and Ara h 6 was mainly mediated by non–cross-reactive antibodies.

Ara h 6 should be considered as allergenic as Ara h 2, and both allergens should be measured as part of an optimal approach for diagnostic testing. Testing IgE-binding to a mixture of 2S-albumins rather than to each separate component may also improve the accuracy of peanut allergy diagnosis.

Diagnostic testing to allergenic components has helped clinicians to categorize clinically relevant reactivity from clinically irrelevant sensitization. Measuring IgE to both Ara h 2 and Ara h 6, specifically as a 2S albumin mixture, could be an additional tool in the allergist’s armamentarium.