Newly Identified Biomarkers Could Help Asthma and Allergy Diagnosis


Genetic biomarkers can be linked to severity and development of asthma.

International researchers have recently collaborated on an in-depth study of genetic biomarkers and their connection to severity and development of asthma.

The study validated the existence of "molecular biomarkers related to asthmatic disease types in peripheral blood samples”.

The team from the Immunology and Allergy departments of The Jimenez Dias Foundation, Virgen del Rocio University Hospital, Can Cecilio University Hospital and the Biomedical Research Networking Center for Respiratory Diseases (CIBERES) in Spain sought to define the specific biomarkers differentiating asthma from allergic reactions in order to establish non-invasive means of predicting disease and disease severity in clinical populations.

In recent years researchers and healthcare professionals focusing on respiratory diseases categorized asthma into endotypes based on features of the disease. However, there has been some difficulty in clearly defining these endotypes due to overlapping symptoms. "It is well-known that reaction to treatment varies between different asthma patients," Selene Baos, PhD, from the Immunology Department of Jimenez Dias Foundation explained.

Baos and team believed that description of these different endotypes might rely on identification of specific biomarkers. According to Baos, biomarker identification may be the key to finding the "signature of a complex underlying pathway or key molecule associated with or playing a role in a particular disease endotype" like asthma. Identification of endotypes could result in targeted therapies and reduce delays in diagnoses for patients with these newly identified biomarkers.

Baos explained that specific asthma therapies targeting patients with T-helper 2 (Th2) biomarkers have already been developed, while other "biologically targeted therapies are still in their infancy."

In the study, Baos and fellow researchers analyzed 94 different genes using quantitative real-time polymerase chain reaction (qRT-PCR) transcripts. qRT-PCR is one of the most sensitive assays for identifying infections and diseases using single or multiple gene expressions. The study used qRT-PCR to analyze gene expression, regulation, and differentiation "in 30 healthy control subjects, 30 patients with non-allergic asthma, 30 with allergic asthma, and 14 pages with allergy (rhinitis) but without asthma."

The resulting data from the gene expression analysis showed there were four clusters of biomarkers, which correlated with the four clinical groups (healthy control, non-allergic asthmatic subjects, asthmatic allergic subjects, and non-asthmatic allergic subjects). Researchers then performed a functional analysis comparing the genetic data of patients in each of the clinical groups to the healthy control groups in an attempt to locate genes specifically related to asthma and allergy.

The study identified four gene clusters that "correlated with the four clinical phenotypes." and analysis of differential gene expression between the four clinical groups revealed 26 statistically relevant genes in subjects with non-allergic asthma, and 69 statistically relevant genes in subjects with allergic asthma. According to study data, many of these genes were highly overexpressed in asthmatic subjects, and many were "differently expressed" in allergic asthmatic subjects.

An additional analysis of genes based on severity of asthma revealed "interesting data" — a large number of highly under expressed genes were evident in patients with severe allergic asthma as compared to the other clinical patients.

Particularly significant was the connection between macrophage scavenger receptor 1 (MRS1) and the patients with allergic and non-allergic asthma. According to Baos, MRS1 protein expression was "the most highly overexpressed gene in NA subjects, mainly in severe asthmatic patients." Similarly, the study found statistically significant links between asthma, severity and interleukin 8 (IL-8), tumor necrosis factor (TNF), and a range of peptidase inhibitors.

The study concluded that genetic identification of biomarkers might be used as a means of introducing endotype-driven diagnostic and prognostic tools for analyzing asthma and allergic phenotypes. The data produced by the researchers could also be useful in developing new therapeutic tools for asthma sufferers.

The article, "Biomarkers Associated with Disease Severity in Allergic and Nonallergic Asthma," appeared in the February 2017 issue of Molecular Immunology.

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