Serological Assessment of Patients Undergoing Peanut Oral Immunotherapy: The Role of IgG4

Peanut oral immunotherapy (OIT) aims to increase the safety of individuals with peanut allergy by gradual exposure to small, measured amounts of peanuts. Many studies use a maintenance dose of 300mg to achieve clinical desensitization. OIT is limited by frequent dose-related adverse reactions, leading to participant withdrawals. Data on immunologic parameters associated with maintenance doses lower than 300mg are limited.
Seventeen peanut-allergic children aged 1 to 17 years were enrolled in a trial (NCT03532360) of low or high-maintenance dose peanut OIT. Patients were randomized to 300mg (N=9) or 30mg (N=8) groups. Blood was drawn at three timepoints: oral food challenge, post-escalation challenge and exit challenge. Serum samples were used for quantitative detection of total peanut- and Arah2-specific immunoglobulin (Ig) E and IgG4 levels by ELISA.
After a median escalation phase of 15 months, peanut-specific-IgG4 significantly increased from a median baseline of 148.55 μg/mL (IQR 68.95-243.41) to 989.09 μg/mL (IQR 392.55-1905.33) (p < 0.05) in the 300mg group and from 58.13 μg/mL (IQR 20.54-303.92) to 277.91 μg/mL (IQR 64.85-634.99) in the 30mg group (p < 0.05). Peanut-specific-IgE did not significantly decrease in either group. The IgG4/IgE ratio significantly increased over the course of peanut OIT in both groups (p < 0.05). From the low-dose and high-dose groups, 6/8 and 6/9 subjects were clinically desensitized respectively.
Both low-dose and high-dose OIT maintenance doses resulted in significant increases in peanut-specific IgG4. Our findings suggest that changes in IgG4, rather than IgE, better reflect clinical desensitization. Large-scale studies are required to establish the role of IgGs versus IgE in OIT.