Cargando…

Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children

We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT....

Descripción completa

Detalles Bibliográficos
Autores principales: Karisola, Piia, Palosuo, Kati, Hinkkanen, Victoria, Wisgrill, Lukas, Savinko, Terhi, Fyhrquist, Nanna, Alenius, Harri, Mäkelä, Mika J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714802/
https://www.ncbi.nlm.nih.gov/pubmed/34975829
http://dx.doi.org/10.3389/fimmu.2021.704633
_version_ 1784624003761045504
author Karisola, Piia
Palosuo, Kati
Hinkkanen, Victoria
Wisgrill, Lukas
Savinko, Terhi
Fyhrquist, Nanna
Alenius, Harri
Mäkelä, Mika J.
author_facet Karisola, Piia
Palosuo, Kati
Hinkkanen, Victoria
Wisgrill, Lukas
Savinko, Terhi
Fyhrquist, Nanna
Alenius, Harri
Mäkelä, Mika J.
author_sort Karisola, Piia
collection PubMed
description We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1–4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization.
format Online
Article
Text
id pubmed-8714802
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-87148022021-12-30 Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children Karisola, Piia Palosuo, Kati Hinkkanen, Victoria Wisgrill, Lukas Savinko, Terhi Fyhrquist, Nanna Alenius, Harri Mäkelä, Mika J. Front Immunol Immunology We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1–4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization. Frontiers Media S.A. 2021-12-15 /pmc/articles/PMC8714802/ /pubmed/34975829 http://dx.doi.org/10.3389/fimmu.2021.704633 Text en Copyright © 2021 Karisola, Palosuo, Hinkkanen, Wisgrill, Savinko, Fyhrquist, Alenius and Mäkelä https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Karisola, Piia
Palosuo, Kati
Hinkkanen, Victoria
Wisgrill, Lukas
Savinko, Terhi
Fyhrquist, Nanna
Alenius, Harri
Mäkelä, Mika J.
Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children
title Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children
title_full Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children
title_fullStr Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children
title_full_unstemmed Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children
title_short Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children
title_sort integrative transcriptomics reveals activation of innate immune responses and inhibition of inflammation during oral immunotherapy for egg allergy in children
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714802/
https://www.ncbi.nlm.nih.gov/pubmed/34975829
http://dx.doi.org/10.3389/fimmu.2021.704633
work_keys_str_mv AT karisolapiia integrativetranscriptomicsrevealsactivationofinnateimmuneresponsesandinhibitionofinflammationduringoralimmunotherapyforeggallergyinchildren
AT palosuokati integrativetranscriptomicsrevealsactivationofinnateimmuneresponsesandinhibitionofinflammationduringoralimmunotherapyforeggallergyinchildren
AT hinkkanenvictoria integrativetranscriptomicsrevealsactivationofinnateimmuneresponsesandinhibitionofinflammationduringoralimmunotherapyforeggallergyinchildren
AT wisgrilllukas integrativetranscriptomicsrevealsactivationofinnateimmuneresponsesandinhibitionofinflammationduringoralimmunotherapyforeggallergyinchildren
AT savinkoterhi integrativetranscriptomicsrevealsactivationofinnateimmuneresponsesandinhibitionofinflammationduringoralimmunotherapyforeggallergyinchildren
AT fyhrquistnanna integrativetranscriptomicsrevealsactivationofinnateimmuneresponsesandinhibitionofinflammationduringoralimmunotherapyforeggallergyinchildren
AT aleniusharri integrativetranscriptomicsrevealsactivationofinnateimmuneresponsesandinhibitionofinflammationduringoralimmunotherapyforeggallergyinchildren
AT makelamikaj integrativetranscriptomicsrevealsactivationofinnateimmuneresponsesandinhibitionofinflammationduringoralimmunotherapyforeggallergyinchildren