HLA-associated outcomes in peanut oral immunotherapy trials identify mechanistic and clinical determinants of therapeutic success

Autor: Kanika Kanchan, Gautam Shankar, Michelle F. Huffaker, Henry T. Bahnson, R Sharon Chinthrajah, Srinath Sanda, Monali Manohar, Hua Ling, Justin E. Paschall, George Du Toit, Ingo Ruczinski, Alkis Togias, Gideon Lack, Kari C. Nadeau, Stacie M. Jones, Gerald T. Nepom, Rasika A. Mathias
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Immunology, Vol 13 (2022)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2022.941839
Popis: RationalePrevious studies identified an interaction between HLA and oral peanut exposure. HLA-DQA1*01:02 had a protective role with the induction of Ara h 2 epitope-specific IgG4 associated with peanut consumption during the LEAP clinical trial for prevention of peanut allergy, while it was a risk allele for peanut allergy in the peanut avoidance group. We have now evaluated this gene-environment interaction in two subsequent peanut oral immunotherapy (OIT) trials - IMPACT and POISED - to better understand the potential for the HLA-DQA1*01:02 allele as an indicator of higher likelihood of desensitization, sustained unresponsiveness, and peanut allergy remission.MethodsWe determined HLA-DQA1*01:02 carrier status using genome sequencing from POISED (N=118, age: 7-55yr) and IMPACT (N=126, age: 12-
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