Hereditary metabolic and immune disorders have more in common than previously thought, according to a new study published in the journal Science ImmunologyThe findings point to a new set of metabolic genes that are important for the function of the immune system’s T cells and offer insights that could improve care for patients with these disorders.
The study examined genes that cause inborn errors of metabolism (disorders of the processes cells use to convert food into energy) and inborn errors of immunity (disorders that affect how the immune system works). These rare and complex diseases are still not fully understood.
“Until now, there were only a small number of genes that appeared on both disease lists, but we found that many more overlap,” said Dr. Andrew Patterson, who led the study as a postdoctoral researcher with Dr. Jeffrey Rathmell 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 mutated.”
The findings suggest that patients with an inborn error of metabolism may also have immune defects that could affect their attention and, conversely, that metabolic defects may contribute to symptoms in patients with inborn errors of metabolism.
“There’s still a lot to learn, but these connections could point to the emergence of different therapies,” said Rathmell, the Cornelius Vanderbilt Professor of Immunobiology and director of the Vanderbilt Immunobiology Center. “Rather than being separate categories, these diseases are part of a continuum; there’s a gray area between them and a potential new class of inborn errors of immunometabolism that cuts across them.”
Patterson and the research team used a CRISPR gene-editing approach to detect immune defects in inborn errors of metabolism genes and metabolic defects in inborn errors of immunity genes. They also analyzed one example of each set (a metabolic gene that had an immune defect and an immunity gene that had a metabolic defect) to further examine the mechanistic impact.
In general, Rathmell’s team is interested in uncovering how metabolic pathways regulate T cell function, with the goal of developing therapies targeting immune-mediated disorders.
“What we’ve done is lay the groundwork 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’ve identified to analyze for their role in T cell function.”
The results are available at Functional Immunogenomics Resources (FIGS) Website so that other researchers can use them.
“If you’re trying to understand the connections between metabolism and immunity, this is a great place to start,” Rathmell said.
Patterson recently joined the faculty at the University of Louisville as an assistant professor of Biochemistry and Molecular Genetics. Vanderbilt collaborators Vivian Gama, PhD, assistant professor of Cell and Developmental Biology, and Janet Markle, PhD, assistant professor of Pathology, Microbiology and Immunology, were major contributors to the study.