Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine?

• Research
• Open Access

• Jill de Wit†View ORCID ID profile,
• 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†Email author and
• the Academic Center of Excellence (ACE) workgroups Allergic Diseases and Rare Immunological Disease Centre (RIDC)

†Contributed equally

Clinical and Translational Allergy20199:34

Abstract

Background

Venn diagram illustrating the overlap of the disease causing genes
of monogenic primary immunodeficiency diseases and the atopy-related genes
identified in the Human Gene Mutation Database

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.

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