To identify why some patients with peanut IgE clinically react to peanut (peanut allergy) while others are tolerant (peanut sensitized) by studying differences in IgE and IgG4 binding to peanut allergen epitopes.

The study population consisted of 108 participants. Fifty-six were classified as peanut allergic, confirmed by either oral food challenge (OFC) or by skin prick test (SPT) wheal greater than 8 mm or peanut specific IgE greater than 15 kU/L; 42 peanut sensitized patients determined by SPT with wheal size ≥1 mm and/or peanut specific IgE ≥ 0.10 kUA/L; and 10 nonsensitized, nonallergic patients.

Synthetic Ara h 1–11 with 15-mer overlapping peptides were printed on microarray slides and incubated with individual patient’s plasma. IgE and IgG4 binding was then measured by immunofluorescence. Using ImmunoCAP, binding of IgE and IgG4 were quantified, and IgG4/IgE ratios were then calculated.

There was no statistically significant difference between total IgE and peanut specifc IgG4 in peanut allergic and peanut sensitized patients. Peanut allergic patients had higher levels of peanut specific IgE, Ara h 1, Ara h 2, and Ara h 3, when compared with peanut sensitized patients (P < .001, P = .007, P < .001, P = .17, respectively). Peanut allergic patients had a higher degree of IgE binding to 7 peptides identified to be associated with Ara h 1, Ara h 2, and Ara h 3. Specific IgE to the four Ara h 2 peptides increased the accuracy of Ara h 2-specific IgE. IgE binding of one peptide on Ara h 5 was higher in peanut sensitized patients when compared with peanut allergic patients, as was IgG4 to one peptide of Ara h 9. Peanut sensitized patients also had elevated IgG4/IgE ratios to 4 out of the 7 peptides.

This study found that there were differences in IgE binding to specific peptides associated with Ara h 1, Ara h 2, and Ara h 3, with increased IgE binding in peanut allergic patients compared with peanut sensitized, nonallergic patients. The accuracy of Ara h 2-specific IgE is increased when used in conjunction with IgE to the 4 peptides of Ara h 2.

Use of IgE to Ara h 2 specific peptides can guide diagnosis of true peanut allergy versus a patient who is only sensitized to peanut. This could be used when making decisions regarding food introduction in patients who report no history of peanut consumption, but test positive on ImmunoCAP. This may help differentiate patients who may benefit from OFC from those who may not need supervised OFC. Improved understanding could also lead to potential treatment options for patients with peanut allergy.