PHOENIX -- An immune system gene variant may affect outcomes with oral immunotherapy treatments (OITs) for peanut allergies, an analysis of three different clinical trials showed.
In the IMPACT study, toddlers ages 12 to <48 months who carried the HLA-DQA1*01:02 allele were more likely to become desensitized to peanuts compared with noncarriers (93% of carriers vs 78% of noncarriers; OR 5.74, P=0.06), reported Kanika Kanchan, PhD, of the Johns Hopkins University School of Medicine in Baltimore, during a pre-recorded presentation at the American Academy of Allergy, Asthma & Immunology annual meeting.
Participants in the IMPACT trial were also more likely to be tolerant to OIT, "albeit to a lesser degree," if they were carriers versus noncarriers (35% vs 22%, OR 1.26, P=0.80), Kanchan noted.
In the POISED trial, a 2019 study looking at the long-term effects of peanut OITs in people ages 7 to 53, carriers of the HLA variant were more likely to reach sustained unresponsiveness and tolerance with OIT.
"Age, baseline characteristics, and HLA genetics may not only be an important part of a mechanism of antigen recognition in peanut allergy, but also potentially relevant for response to OIT," Kanchan said.
The POISED study had two treatment arms. Both arms built up tolerance to 4,000 mg of peanut powder; one arm then stopped peanut OIT for the following year (Peanut-0 group) and the other received 300 mg of peanut powder daily (Peanut-300 group).
Of the carriers in the Peanut-0 group, 52% achieved sustained unresponsiveness to peanuts compared with 31% of noncarriers (OR 2.32, P=0.19). As for the Peanut-300 group, 80% of carriers achieved tolerance versus 61% of noncarriers (OR 1.28, P=0.86).
"Based on these data, we can conclude that HLA carriers are more likely to achieve desensitization, tolerance, and sustained unresponsiveness, and this is a consistent pattern across both studies," Kanchan said.
Their results support previous findings from the LEAP study, which were reported last month in the Journal of Clinical Investigation by Kanchan and colleagues. They found that carriers of the HLA-DQA1*01:02 allele who consumed peanuts had higher levels of immunoglobulin G4 (IgG4) and were protected from peanut allergy. In contrast, carriers who avoided peanuts had no elevation in IgG4 levels and were at risk for peanut allergy.
In the IMPACT study, IgG4 profiles were similar to those reported in LEAP, Kanchan said, noting in particular the association with Ara h 2, a peanut component found in those with peanut allergies.
However, that association was not found in either treatment group in the POISED study, suggesting that age is an important factor, since the participants in the IMPACT study were much younger than those in the POISED study, she pointed out.
The analysis used whole-genome sequencing data from 126 patients in the IMPACT study, 24% of whom were carriers of the HLA variant, and 118 in the POISED study, 20% of whom were carriers.
"Given the small sample sizes, we did not attain statistical significance for any single observation, but we note a highly consistent pattern for both IMPACT and POISED," Kanchan acknowledged.
Kanchan reported no disclosures.
American Academy of Allergy, Asthma & Immunology