Metabolic and Immune Disorders: A Study on Gene Overlap in Rare Diseases

The genes responsible for inborn errors of immunity (disorders affecting immune system function) and metabolism (disorders of the processes that cells utilize to transform food into energy) were investigated. Rare and complex diseases are not well understood(1^✔ ✔Trusted Source
Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities

Go to source). A recent study published in the journal Science Immunology suggests that inherited illnesses of metabolism and immunology have more similarities than previously thought. The results provide information that may help patients with these illnesses receive better care by pointing to a novel collection of metabolic genes that are critical for immune system T cell function.

Gene Overlaps Identified

“There had previously been only a small number of genes that were on both lists of diseases, but we found that many more have overlap,” said Andrew Patterson, PhD, who led the study as a postdoctoral fellow working with Jeffrey Rathmell, PhD, at Vanderbilt University Medical Center. “Our study showed that a large number of genes associated with inborn errors of metabolism can also potentially affect T cell function when they are mutated.”

The findings suggest that patients with an inborn error of metabolism may also have immune defects that could impact their care, and conversely, that metabolic defects may contribute to symptoms in patients with inborn errors of immunity.

New Perspective on Rare Diseases Classification

“There’s a lot more that will have to be learned, but these connections might point to different therapies,” said Rathmell, Cornelius Vanderbilt Professor of Immuno-biology and director of the Vanderbilt Center for Immunobiology. “Rather than different categories, these diseases are part of a continuum; there’s a gray zone between them and a potential new class of inborn errors of immuno-metabolism that intersects the two”.

Patterson and the research team used a gene-editing CRISPR approach to screen the inborn errors of metabolism genes for immune defects and the inborn errors of immunity genes for metabolic defects. CRISPR or clustered regularly interspaced short palindromic repeats is a genetic engineering technique that allows scientists to modify the DNA of living organisms.They further analyzed one example from each set one metabolic gene that had an immune defect; and one immunity gene that had a metabolic defect to more carefully examine the mechanistic impact.

Overall, Rathmell’s team is interested in discovering how metabolic pathways regulate T cell function, to develop targeted therapies for immune-mediated disorders.

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“What we’ve done is lay the foundation for further investigation,” Patterson said. “The two examples we studied in detail point to new biology and new mechanisms, and there are hundreds of other genes we identified to analyze for their roles in T cell function”.

Reference:

1. Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities - (https:www.science.org/doi/10.1126/sciimmunol.adh0368)

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Source-Eurekalert