Abstract
This review summarises recent advances in characterising the
transcriptional pathways associated with outcomes following Oral
Immunotherapy.
Recent technological advances including single-cell sequencing are
transforming the ways in which the transcriptional landscape is
understood. The application of these technologies is still in its
infancy in food allergy but here we summarise current understanding of
gene expression changes following oral immunotherapy for food allergy
and specific signatures underpinning the different clinical outcomes of
desensitisation and remission (sustained unresponsiveness).
T helper 2A cells have been identified as a cell type which correlates
with disease activity and is modified by treatment. Molecular features
at study entry may differentiate individuals who achieve more positive
outcomes during OIT. Recent findings point to T cell anergy and Type 1
interferon pathways as potential mechanisms supporting redirection of
the allergen-specific immune response away from allergy towards
remission.
Despite these developments in our understanding of immune mechanisms
following OIT, there are still significant gaps. Additional studies
examining immune signatures associated with long term and well-defined
clinical outcomes are required to gain a more complete understanding of
the pathways leading to remission of allergy, in order to optimise
treatments and gain improved outcomes for patients.
Key words : Food allergy; Transcriptomics; Systems biology; Oral
Immunotherapy; Gene expression; Remission; Desensitisation
Key Message: This review summarises the current understanding
of immune changes associated with food oral immunotherapy (OIT),
focusing on new discoveries gained from state of the art transcriptomic
approaches. Recent computational and technological advances have
transformed our understanding of immune mechanisms driving food allergy,
desensitisation and remission of food allergy. There is compelling
evidence that T cell anergy and type I interferons play important roles
in determining clinical outcomes following OIT. Future studies with
larger sample sizes, from individuals with well-defined clinical
outcomes and longitudinal sampling are needed to provide high quality
evidence of key mechanisms and further elucidate novel biomarkers of
treatment response.