Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine?
Abstract Background The atopic syndrome consists of heterogeneous manifestations, in which multiple associated genetic loci have recently been identified. It is hypothesized that immune dysregulation plays a role in the pathogenesis. In primary immunodeficiency diseases (PIDs), which are often monog...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2019-07-01
|
Series: | Clinical and Translational Allergy |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s13601-019-0273-8 |
id |
doaj-78337cf0578f4e428b3c719ef009a7a6 |
---|---|
record_format |
Article |
spelling |
doaj-78337cf0578f4e428b3c719ef009a7a62021-09-02T12:16:34ZengWileyClinical and Translational Allergy2045-70222019-07-019111010.1186/s13601-019-0273-8Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine?Jill de Wit0Rogier T. A. van Wijck1Virgil A. S. H. Dalm2Kristen L. Snyder3Joan E. E. Totté4Suzanne G. M. A. Pasmans5Peter J. van der Spek6the Academic Center of Excellence (ACE) workgroups Allergic Diseases and Rare Immunological Disease Centre (RIDC)Department of Dermatology, Erasmus MC University Medical CenterDepartment of Internal Medicine, Division of Clinical Immunology, Erasmus MC University Medical CenterDepartment of Internal Medicine, Division of Clinical Immunology, Erasmus MC University Medical CenterDepartment of Pathology, Division of Bioinformatics, Erasmus MC University Medical CenterDepartment of Dermatology, Erasmus MC University Medical CenterDepartment of Dermatology, Erasmus MC University Medical CenterDepartment of Pathology, Division of Bioinformatics, Erasmus MC University Medical CenterAbstract Background The atopic syndrome consists of heterogeneous manifestations, in which multiple associated genetic loci have recently been identified. It is hypothesized that immune dysregulation plays a role in the pathogenesis. In primary immunodeficiency diseases (PIDs), which are often monogenic immunodysregulation disorders, the atopic syndrome is a frequently occurring comorbidity. Based on the genetic defects in PIDs, novel gene/pathway-targeted therapies have been evaluated, which could be relevant in the atopic syndrome as well. Therefore, we aimed to define subclasses within the atopic syndrome based on the expression profiles of immune cell lineages of healthy mice. Methods Overlap between known atopy-related genes as described in the Human Gene Mutation Database and disease-causing genes of monogenic PIDs was evaluated. Clusters of atopy-related genes were based on the overlap in their co-expressed genes using the gene expression profiles of immune cell lineages of healthy mice from the Immunological Genome Project. We analyzed pathways involved in the atopic syndrome using Ingenuity Pathway Analysis. Results Twenty-two (5.3%) genes were overlapping between the atopy-related genes (n = 160) and PID-related genes (n = 278). We identified seven distinct clusters of atopy-related genes. Functional pathway analysis of all atopy-related genes showed relevance of T helper cell-mediated pathways. Conclusions This study shows a model to define clusters within the atopic syndrome based on gene expression profiles of immune cell lineages. Our results support the hypothesis that both genetic mechanisms and immune dysregulation play a role in the pathogenesis. It also opens up the possibility for novel therapeutic targets and a more tailored approach towards personalized medicine.http://link.springer.com/article/10.1186/s13601-019-0273-8AtopyEndotypesPersonalized medicinePrimary immunodeficiency disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jill de Wit Rogier T. A. van Wijck Virgil A. S. H. Dalm Kristen L. Snyder Joan E. E. Totté Suzanne G. M. A. Pasmans Peter J. van der Spek the Academic Center of Excellence (ACE) workgroups Allergic Diseases and Rare Immunological Disease Centre (RIDC) |
spellingShingle |
Jill de Wit Rogier T. A. van Wijck Virgil A. S. H. Dalm Kristen L. Snyder Joan E. E. Totté Suzanne G. M. A. Pasmans Peter J. van der Spek the Academic Center of Excellence (ACE) workgroups Allergic Diseases and Rare Immunological Disease Centre (RIDC) Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine? Clinical and Translational Allergy Atopy Endotypes Personalized medicine Primary immunodeficiency disease |
author_facet |
Jill de Wit Rogier T. A. van Wijck Virgil A. S. H. Dalm Kristen L. Snyder Joan E. E. Totté Suzanne G. M. A. Pasmans Peter J. van der Spek the Academic Center of Excellence (ACE) workgroups Allergic Diseases and Rare Immunological Disease Centre (RIDC) |
author_sort |
Jill de Wit |
title |
Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine? |
title_short |
Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine? |
title_full |
Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine? |
title_fullStr |
Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine? |
title_full_unstemmed |
Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine? |
title_sort |
molecular clustering of genes related to the atopic syndrome: towards a more tailored approach and personalized medicine? |
publisher |
Wiley |
series |
Clinical and Translational Allergy |
issn |
2045-7022 |
publishDate |
2019-07-01 |
description |
Abstract Background The atopic syndrome consists of heterogeneous manifestations, in which multiple associated genetic loci have recently been identified. It is hypothesized that immune dysregulation plays a role in the pathogenesis. In primary immunodeficiency diseases (PIDs), which are often monogenic immunodysregulation disorders, the atopic syndrome is a frequently occurring comorbidity. Based on the genetic defects in PIDs, novel gene/pathway-targeted therapies have been evaluated, which could be relevant in the atopic syndrome as well. Therefore, we aimed to define subclasses within the atopic syndrome based on the expression profiles of immune cell lineages of healthy mice. Methods Overlap between known atopy-related genes as described in the Human Gene Mutation Database and disease-causing genes of monogenic PIDs was evaluated. Clusters of atopy-related genes were based on the overlap in their co-expressed genes using the gene expression profiles of immune cell lineages of healthy mice from the Immunological Genome Project. We analyzed pathways involved in the atopic syndrome using Ingenuity Pathway Analysis. Results Twenty-two (5.3%) genes were overlapping between the atopy-related genes (n = 160) and PID-related genes (n = 278). We identified seven distinct clusters of atopy-related genes. Functional pathway analysis of all atopy-related genes showed relevance of T helper cell-mediated pathways. Conclusions This study shows a model to define clusters within the atopic syndrome based on gene expression profiles of immune cell lineages. Our results support the hypothesis that both genetic mechanisms and immune dysregulation play a role in the pathogenesis. It also opens up the possibility for novel therapeutic targets and a more tailored approach towards personalized medicine. |
topic |
Atopy Endotypes Personalized medicine Primary immunodeficiency disease |
url |
http://link.springer.com/article/10.1186/s13601-019-0273-8 |
work_keys_str_mv |
AT jilldewit molecularclusteringofgenesrelatedtotheatopicsyndrometowardsamoretailoredapproachandpersonalizedmedicine AT rogiertavanwijck molecularclusteringofgenesrelatedtotheatopicsyndrometowardsamoretailoredapproachandpersonalizedmedicine AT virgilashdalm molecularclusteringofgenesrelatedtotheatopicsyndrometowardsamoretailoredapproachandpersonalizedmedicine AT kristenlsnyder molecularclusteringofgenesrelatedtotheatopicsyndrometowardsamoretailoredapproachandpersonalizedmedicine AT joaneetotte molecularclusteringofgenesrelatedtotheatopicsyndrometowardsamoretailoredapproachandpersonalizedmedicine AT suzannegmapasmans molecularclusteringofgenesrelatedtotheatopicsyndrometowardsamoretailoredapproachandpersonalizedmedicine AT peterjvanderspek molecularclusteringofgenesrelatedtotheatopicsyndrometowardsamoretailoredapproachandpersonalizedmedicine AT theacademiccenterofexcellenceaceworkgroupsallergicdiseasesandrareimmunologicaldiseasecentreridc molecularclusteringofgenesrelatedtotheatopicsyndrometowardsamoretailoredapproachandpersonalizedmedicine |
_version_ |
1721175628670042112 |