March 8, 2019
A follow-up analysis of the participants from ITN’s LEAP (Learning Early About Peanut Allergy) Study has identified a strong association between the development of peanut allergy and the MALT1 gene. These findings were recently published in the February 27th issue of the Journal of Allergy and Clinical Immunology.
The outcome of the LEAP trial led to a change in pediatric guidelines for the early introduction of peanut into the diet of infants as an effective strategy for the prevention of peanut allergy. The study found that introduction of peanut protein in the first 4-11 months of life significantly decreased the frequency of developing peanut allergy later in childhood in children at high risk for developing peanut allergy.
In this follow-up study, whole genome sequencing (WGS) was conducted in order to identify genetic factors involved in the development of peanut allergy among LEAP participants. Since the introduction of peanut was so successful at reducing peanut allergy, genome-wide associations for peanut allergy were assessed in participants from the avoidance arm. In this discovery analysis, the MALT1 (mucosa-associated lymphoid tissue lymphoma translocation) gene was found to have the highest association with peanut allergy, with the peak associated single nucleotide variant (SNV) being rs57265082. MALT1 rs57265082 carriers in the avoidance group were at increased risk for developing peanut allergy with 58.6% of carriers becoming peanut allergic compared to just 12.7% of non-carriers.
In the avoidance group, the levels of peanut-specific IgE between carriers and non-carriers differed, with rs57265082 carriers having the highest peanut-specific IgE levels compared to non-carriers. However, the MALT1 variant was significantly associated with peanut allergy even within the subset of sensitized peanut avoiders further supporting its role as a risk factor for peanut allergy and not just sensitization. In the consumption group, it was found that early dietary peanut exposure was equally effective at preventing peanut allergy and reducing peanut-specific IgE in both MALT1 carriers and non-carriers.
These results suggest the MALT1 gene is an independent risk factor for peanut allergy and implicates the MALT1 pathway in the progression to peanut allergy if peanut is avoided.
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