%0 Clinical Trial, Phase I
%T Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3).
%A Syed A
%A Garcia MA
%A Lyu SC
%A Bucayu R
%A Kohli A
%A Ishida S
%A Berglund JP
%A Tsai M
%A Maecker H
%A O'Riordan G
%A Galli SJ
%A Nadeau KC
%J J Allergy Clin Immunol
%V 133
%N 2
%D Feb 2014
%M 24636474
%F 14.29
%R 10.1016/j.jaci.2013.12.1037
%X <B>BACKGROUND: </B>The mechanisms contributing to clinical immune tolerance remain incompletely understood. This study provides evidence for specific immune mechanisms that are associated with a model of operationally defined clinical tolerance.<BR><B>OBJECTIVE: </B>Our overall objective was to study laboratory changes associated with clinical immune tolerance in antigen-induced T cells, basophils, and antibodies in subjects undergoing oral immunotherapy (OIT) for peanut allergy.<BR><B>METHODS: </B>In a phase 1 single-site study, we studied participants (n = 23) undergoing peanut OIT and compared them with age-matched allergic control subjects (n = 20) undergoing standard of care (abstaining from peanut) for 24 months. Participants were operationally defined as clinically immune tolerant (IT) if they had no detectable allergic reactions to a peanut oral food challenge after 3 months of therapy withdrawal (IT, n = 7), whereas those who had an allergic reaction were categorized as nontolerant (NT; n = 13).<BR><B>RESULTS: </B>Antibody and basophil activation measurements did not statistically differentiate between NT versus IT participants. However, T-cell function and demethylation of forkhead box protein 3 (FOXP3) CpG sites in antigen-induced regulatory T cells were significantly different between IT versus NT participants. When IT participants were withdrawn from peanut therapy for an additional 3 months (total of 6 months), only 3 participants remained classified as IT participants, and 4 participants regained sensitivity along with increased methylation of FOXP3 CpG sites in antigen-induced regulatory T cells.<BR><B>CONCLUSIONS: </B>In summary, modifications at the DNA level of antigen-induced T-cell subsets might be predictive of a state of operationally defined clinical immune tolerance during peanut OIT.