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 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. Electronic supplementary material The online version of this article (10.1186/s13601-019-0273-8) contains supplementary material, which is available to authorized users.

Food allergy as one of the faces of primary immunodeficiency

“…In general, the rates of FA and anaphylaxis in patients with HIES are significantly lower than in patients with atopic dermatitis and similarly elevated IgE levels (FA 38 percent versus 58 percent and food-induced anaphylaxis 8 percent versus 33 percent) (Figure 1) [23].…”

Grand challenges in genetics and epidemiology of allergic diseases: from genome to exposome and back

“…Preventing severe cases implies, again, predicting those cases. The study of phenotypes and endotypes of allergic diseases and how to predict them (21) can help in choosing the most efficacious approach to prevention and management. Genetics is fundamental in this respect (22).…”

“…We are trying to understand how certain genes are switched on or off, either by other genes or through interaction with the environment via epigenetic mechanisms (25). We are also trying to comprehend how the transcription of such genes is made and potentially modified (21).…”

Highlights and recent developments in allergic diseases in EAACI journals (2019)

“…Immune dysregulation may play a role in the pathogenesis. Molecular clustering of genes related to the atopic syndrome was carried out [ 29 ]. Twenty-two (5.3%) genes were overlapping between the atopy-related genes (n = 160) and primary immunodeficiency disease-related genes (n = 278).…”