Dataset Information

Clinical efficacy and immune regulation with peanut oral immunotherapy.

ABSTRACT:

Background

Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported.

Objective

The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT.

Methods

Children with peanut allergy underwent an OIT protocol including initial day escalation, buildup, and maintenance phases, and then oral food challenge. Clinical response and immunologic changes were evaluated.

Results

Of 29 subjects who completed the protocol, 27 ingested 3.9 g peanut protein during food challenge. Most symptoms noted during OIT resolved spontaneously or with antihistamines. By 6 months, titrated skin prick tests and activation of basophils significantly declined. Peanut-specific IgE decreased by 12 to 18 months, whereas IgG(4) increased significantly. Serum factors inhibited IgE-peanut complex formation in an IgE-facilitated allergen binding assay. Secretion of IL-10, IL-5, IFN-gamma, and TNF-alpha from PBMCs increased over a period of 6 to 12 months. Peanut-specific forkhead box protein 3 T cells increased until 12 months and decreased thereafter. In addition, T-cell microarrays showed downregulation of genes in apoptotic pathways.

Conclusion

Oral immunotherapy induces clinical desensitization to peanut, with significant longer-term humoral and cellular changes. Microarray data suggest a novel role for apoptosis in OIT.

SUBMITTER: Jones SM

PROVIDER: S-EPMC2725434 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Publications

Clinical efficacy and immune regulation with peanut oral immunotherapy.

Jones Stacie M SM Pons Laurent L Roberts Joseph L JL Scurlock Amy M AM Perry Tamara T TT Kulis Mike M Shreffler Wayne G WG Steele Pamela P Henry Karen A KA Adair Margaret M Francis James M JM Durham Stephen S Vickery Brian P BP Zhong Xiaoping X Burks A Wesley AW

The Journal of allergy and clinical immunology 20090703 2

<h4>Background</h4>Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported.<h4>Objective</h4>The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT.<h4>Methods</h4>Children with peanut allergy underwent an OIT protocol including initial day escalation, buildup, and maintenance phases, and then oral food ...[more]

PMID: 19577283

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Project description: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-<48mo). We tested for association with remission, sustained unresponsiveness (SU), and desensitization in the OIT groups, as well as peanut component specific IgG4 (psIgG4) using generalized linear models and adjusting for relevant covariates and ancestry.ResultsWhile not quite statistically significant, a higher proportion of HLA-DQA1*01:02 carriers receiving OIT in IMPACT were desensitized (93%) compared to non-carriers (78%); odds ratio (OR)=5.74 (p=0.06). In this sample we also observed that a higher proportion of carriers achieved remission (35%) compared to non-carriers (22%); OR=1.26 (p=0.80). In POISED, carriers more frequently attained continued desensitization (80% versus 61% among non-carriers; OR=1.28, p=0.86) and achieved SU (52% versus 31%; OR=2.32, p=0.19). psIgG4 associations with HLA-DQA1*01:02 in the OIT arm of IMPACT which included younger study subjects recapitulated patterns noted in LEAP, but no associations of note were observed in the older POISED study subjects.ConclusionsFindings across three clinical trials show a pattern of a gene environment interaction between HLA and oral peanut exposure. Age, and prior sensitization contribute additional determinants of outcomes, consistent with a mechanism of restricted antigen recognition fundamental to driving protective immune responses to OIT.

Dataset Information

Clinical efficacy and immune regulation with peanut oral immunotherapy.

Background

Objective

Methods

Results

Conclusion

Publications

Clinical efficacy and immune regulation with peanut oral immunotherapy.

Similar Datasets

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