Rare Diseases Highlight Connections Between Metabolism and Immunity

A recent study published in Science Immunology reveals significant connections between inherited diseases of metabolism and immunity. Researchers found a new group of metabolic genes essential for the functioning of T cells in the immune system. These insights could enhance the care of patients afflicted with these disorders.

The study focused on the genes responsible for inborn errors of metabolism, related to how cells convert food into energy, and inborn errors of immunity, which compromise immune system performance. These rare diseases are complex and not yet fully understood.

Andrew Patterson, Ph.D., who led the research at Vanderbilt University Medical Center, noted, "Previously, only a handful of genes appeared on both disease lists; we've discovered many more with overlap." He stated, "This investigation revealed that several genes linked to metabolic errors can also influence T cell function when mutated."

The research indicates that patients with metabolic disorders might also possess immune deficiencies that could complicate their treatment. Inversely, metabolic dysfunctions might influence symptoms in those with disorders of immunity.

"There’s much more to uncover, but these findings could point to innovative therapies," remarked Jeffrey Rathmell, Ph.D., Cornelius Vanderbilt Professor of Immunobiology. He further explained, "Instead of viewing these conditions as separate categories, they form a continuum, suggesting a potential new class of inborn errors of immunometabolism that bridges both fields."

Patterson and his team employed a CRISPR gene-editing method to screen for immune defects in metabolism genes and metabolic issues in immunity genes. They conducted detailed analyses of one gene from each category—one metabolic gene with an associated immune defect and one immune gene displaying metabolic defects.

Overall, Rathmell's team aims to understand how metabolic pathways regulate T cell function, directing their efforts towards targeted therapies for immune-mediated disorders.

"We’ve laid a foundation for deeper research," Patterson stated. "The two cases we examined closely indicate new biological mechanisms, with many other genes pending further exploration for their T cell roles."

The findings are shared on a dedicated website for wider research dissemination.

Rathmell concluded, "If you're keen to explore the interactions between metabolism and immunity, this resource serves as a valuable starting point."

Patterson has recently taken a faculty position at the University of Louisville as an assistant professor of Biochemistry and Molecular Genetics. Key collaborators from Vanderbilt include Vivian Gama, Ph.D., and Janet Markle, Ph.D., who contributed significantly to the study.

Earlier SSP wrote about the new insights into the aging immune system.