Deciphering immune response

French researchers offer new global approach for predicting individual immune responses

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PARIS—Although each person’s response to infection is highly variable and often a mystery, current genetics and technology have uncovered a way to predict individual immune responses, due to a “new approach” by the Milieu Intérieur Consortium, led by researchers at Institut Pasteur—Dr. Matthew Albert of the Immunobiology of Dendritic Cells Unit and Dr. Lluis Quintana-Murci of the Human Evolutionary Genetics Unit—in seeking to establish the parameters that characterize the immune system of healthy individuals and its natural variability.
In a study published August 25 in Cell Reports, co-authored by Magnus Fontes of Lund University in Sweden and International Group for Data Analysis at Institut Pasteur, along with one of bioinformatics software company Qlucore’s founders, the researchers analyzed the inflammatory response at the gene expression level in blood samples from healthy individuals, which reproduces the conditions of in-vivo stimulation.
What the study authors found is that the immune response to complex stimuli such as bacteria, viruses and fungi could be defined and distinguished based on a small number of genes induced by four key immune proteins or cytokines.
As few as 44 genes that were identified by machine learning techniques could explain the variance present within such diverse immune responses. At a time of high-throughput sequencing approaches which create huge challenges for data analysis and medical applications, this study suggests that simplified approaches—if properly targeted—may provide more effective solutions with easier clinical translation.
“The next step is to push this to a global study to be able to include more genetic and environmental variability,” Fontes says.
Furthermore, the study highlights that the utilization of highly standardized techniques for all steps (including sample collection, sample preparation and data analysis) has resulted in the generation of higher quality and more informative data.
“We are excited by the results of this study which demonstrated that a relatively small subset of identified genes could explain the variability in responses to different complex immune stimuli,” states Dr. Darragh Duffy, an immunologist and manager of the Milieu Interieur Consortium.
“In support of the published article, reference values are provided for each immune stimuli which reflects the natural variation of immune responses in humans,” the authors state in the Cell Reports paper. “An online application was also released which provides an opportunity for the scientific community to exploit these data and to explore which genes are induced by a variety of immune stimuli.”
“This newly established approach is now being applied to the 1,000 healthy donors within the Milieu Intérieur cohort, which will enable the dissection of how age, gender, environment, lifestyle, and genetics contribute to variable immune responses,” the authors state. “This is a first necessary step on the path towards precision medicine approaches.”
While the immune system is “highly complex and responses are known to vary across individuals and populations, medical practices and public health policies remain based on a single model of patient care and drug development,” according to the study authors. “The Milieu Intérieur project was initiated specifically to address this discrepancy.”
The Milieu Intérieur project “is poised to have a strong impact on public health, as the data generated will greatly improve our understanding of individual variability in immune responses,” the authors state. “In doing so, we will provide new strategies for adapting treatments with a view to developing a personalized approach to patient care.”
The Milieu Intérieur project is an ambitious population-based study coordinated by the Institut Pasteur with the objective to dissect the interplay between genetics and environment and their impact on the immune system.
This project is named after the French physiologist Claude Bernard’s concept of milieu intérieur and aims to establish the determinants of a healthy immune response by identifying genetic and environmental factors that contribute to the observed heterogeneity of immune responses. Restoring the “personal” in medical care is a major challenge for medicine and the driving vision of the project.
Several of the data analyses in this study were carried out using Qlucore Omics Explorer. Most of the upstream analyses in the study can quickly be reproduced using Qlucore Omics Explorer, directly downloading the data from Gene Expression Omnibus. This work is one example of how Qlucore Omics Explorer is used by scientists, who can browse an extensive list of links to more than 300 scientific articles from peer-reviewed journals written by Qlucore clients.

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