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A new study published in the journal Science Immunology reveals that there is more overlap between inherited diseases of metabolism and immunity than previously recognized. The researchers, led by Dr. Andrew Patterson and Dr. Jeffrey Rathmell of Vanderbilt University Medical Center, investigated genes that cause inborn errors of metabolism and inborn errors of immunity. These rare and complex diseases are not fully understood, but the study found that a large number of genes associated with inborn errors of metabolism can also potentially affect T cell function when mutated. This suggests that patients with metabolic disorders may also have immune defects, and vice versa, highlighting the need for improved care for these patients.

The study suggests that patients with inborn errors of metabolism may have immune defects that could impact their care, and metabolic defects may contribute to symptoms in patients with inborn errors of immunity. Dr. Rathmell, who is the director of the Vanderbilt Center for Immunobiology, believes that these diseases are part of a continuum and that there is a potential new class of inborn errors of immunometabolism that intersects the two categories. 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. Further analysis of one example from each set revealed new insights into the mechanistic impact of these mutations.

Dr. Rathmell’s team is particularly interested in understanding how metabolic pathways regulate T cell function, with the goal of developing targeted therapies for immune-mediated disorders. Dr. Patterson emphasized that the study has laid the foundation for further investigation into the hundreds of other genes identified for their roles in T cell function. The findings have been made available on the Functional ImmunoGenomices reSource (FIGS) website for other researchers to utilize. This research provides a starting point for understanding the connections between metabolism and immunity, offering potential new avenues for therapeutic interventions.

Dr. Patterson, who recently joined the faculty of the University of Louisville, worked closely with Vanderbilt collaborators Dr. Vivian Gama and Dr. Janet Markle on this study. The team’s detailed investigation of two specific genes revealed new biology and mechanisms that could lead to novel treatment strategies for patients with inherited diseases of metabolism and immunity. By identifying the overlap between these two types of disorders, the study opens up possibilities for targeted therapies that address both metabolic and immune defects in patients. This research highlights the importance of understanding the relationship between metabolism and immunity in order to provide more effective care for patients with these complex and rare diseases.

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