Peanut Oral Immunotherapy Yields Distinct IgE, IgG4 Profiles in Kids After 5 Years

Yamini Virkud, MD, FAAAI, MPH

Credit: UNC Health

At least 5 years after the IMPACT study, children who had undergone peanut oral immunotherapy maintained different allergen-specific IgE and IgG4 profiles than children who had taken placebo.¹ The study is a late-breaker at the 2025 American Academy of Allergy, Asthma, & Immunotherapy (AAAAI) annual meeting in San Diego from February 28 through March 3.

“These findings suggest that the early adoption of peanut [oral immunotherapy has lasting immunologic impact correlating with clinical outcomes,” wrote investigators, led by Yamini Virkud, MD, FAAAI, MPH, from the University of North Carolina, Chapel Hill.

The IMPACT trial demonstrated the success of peanut oral immunotherapy in terms of desensitization, and in some cases, remission, in children 1 – 3 years old.² Investigators sought to expand on IMPACT, assessing the long-term effects of early oral immunotherapy on allergen-specific antibody profiles.¹ The team had follow-up data on 51 of 143 IMPACT participants (35%) from 5 – 7 years following IMPACT.

Investigators measured plasma antibody concentrations for total IgE peanut-specific IgE and IgG4 and Ara h 2 specific IgE and IgG4. They compared median concentrations between peanut oral immunotherapy and placebo, desensitization, and remission, desensitization and non-remission, non-desensitization and non-remission, and current peanut consumers and non-consumers.

The analysis revealed that 5 – 7 years after IMPACT, children treated with peanut oral immunotherapy maintained lower peanut-specific IgE (3.6 vs 18.7 kUA/L; P = .002) and Ara h 2 specific IgE (1.0 vs 7.0 kUA/L; P < .001) compared with children who had received placebo. Moreover, children about 6 years following peanut oral immunotherapy had greater ratios of peanut IgG4 IgE (P = .004) to Arah2 IgG4 (P = .001), indicating a shift to immune tolerance.

Furthermore, children who reached remission had the lowest peanut-specific IgE (2.0 vs 3.5; P = .02 kUA/L) and Arah2 IgE (0.9 vs 1.0 kUA/L; P = .002) compared with children who were desensitized or non-desensitized. These children also had the greatest IgG4 to IgE ratio (P = .007). Both findings suggest children who achieved remission on peanut oral immunotherapy had a stronger immunological shift toward tolerance.

Non-responders to oral immunotherapy had the greatest peanut-specific IgE (17.6) and Arah2 IgE levels (6.2), showing they remained allergic. Children who continued eating peanuts had greater levels of protective IgG4 (P < .001) and Arah2-IgG4 (P < .0001) but lower IgE (P ≤ .001) and Arah2-IgE (P ≤ .001), indicating that ongoing exposure may help maintain tolerance.

“Five plus years after the IMPACT study, children maintained differences in allergen-specific IgE and IgG4 profiles when comparing active versus placebo, consumers versus non-consumers, and by remission status,” investigators concluded.

References

1. Virkud, Y, Dantzer, J, Cox, A, et al. Long-Term Assessment of Antibody Profiles after the IMPACT Peanut Oral Immunotherapy Trial: Findings from the IMPACT-PLuS Follow-up. Late breaker presented at the AAAAI 2025 in San Diego from February 28 through March 3.

2. Jones SM, Kim EH, Nadeau KC, Nowak-Wegrzyn A, Wood RA, Sampson HA, Scurlock AM, Chinthrajah S, Wang J, Pesek RD, Sindher SB, Kulis M, Johnson J, Spain K, Babineau DC, Chin H, Laurienzo-Panza J, Yan R, Larson D, Qin T, Whitehouse D, Sever ML, Sanda S, Plaut M, Wheatley LM, Burks AW; Immune Tolerance Network. Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study. Lancet. 2022 Jan 22;399(10322):359-371. doi: 10.1016/S0140-6736(21)02390-4. PMID: 35065784; PMCID: PMC9119642.