WASHINGTON: A new study suggests that inherited immune and metabolism disorders are more similar than previously thought. The findings provide new information that may help better care for patients with these diseases by highlighting a new collection of metabolic genes that are critical for the immune system. T cell activity.
The results of the study were published in the journal Science Immunology.
The study examined the genes that congenital defects of immunity, these are diseases that affect immune system Function and inborn errors of metabolism, i.e. disorders of the mechanisms by which cells convert food into energy. We do not yet fully understand these rare and complex disorders.
“Previously, there were only a few genes that were on both disease lists, but we found that there is much more overlap,” said Dr. Andrew Patterson, who led the study as a postdoctoral fellow at Vanderbilt University Medical Center and worked with Dr. Jeffrey Rathmell. “Our study has shown that a large number of genes associated with inborn errors of metabolism may also have the potential to impair T cell function when mutated.”
The results suggest that patients with inborn errors of metabolism may also have immune deficiencies that could impact their treatment, and conversely that metabolic defects may contribute to symptoms in patients with inborn immunodeficiencies.
“There is much more to learn, but these connections could point to different therapies,” said Rathmell, Cornelius Vanderbilt Professor of Immunobiology and director of the Vanderbilt Center for Immunobiology. “Rather than forming distinct categories, these diseases are part of a continuum; there is a gray area between them and a potential new class of inborn errors of immune metabolism that overlaps the two.”
Patterson and the research team used a CRISPR gene editing approach to examine the inborn errors of metabolism genes for immune defects and the inborn errors of immunity genes for metabolism defects. They also analyzed one example from each set—a metabolism gene with an immune defect; an immunity gene with a metabolism defect—to examine the mechanistic effects in more detail.
Overall, Rathmell’s team is interested in understanding how metabolic pathways regulate T cell function with the goal of developing targeted therapies for immune-mediated diseases.
“We have laid the groundwork for further investigation,” said Patterson. “The two examples we have studied in detail point to new biological events and new mechanisms. In addition, we have identified hundreds of other genes whose role in T cell function needs to be analyzed.”
“If you’re trying to understand the links between metabolism and immunity, this is a good starting point,” Rathmell said.
Patterson recently joined the University of Louisville as an assistant professor of biochemistry and molecular genetics. Vanderbilt collaborators Vivian Gama, PhD, associate professor of cell and developmental biology, and Janet Markle, PhD, assistant professor of pathology, microbiology and immunology, made significant contributions to the study.
The results of the study were published in the journal Science Immunology.
The study examined the genes that congenital defects of immunity, these are diseases that affect immune system Function and inborn errors of metabolism, i.e. disorders of the mechanisms by which cells convert food into energy. We do not yet fully understand these rare and complex disorders.
“Previously, there were only a few genes that were on both disease lists, but we found that there is much more overlap,” said Dr. Andrew Patterson, who led the study as a postdoctoral fellow at Vanderbilt University Medical Center and worked with Dr. Jeffrey Rathmell. “Our study has shown that a large number of genes associated with inborn errors of metabolism may also have the potential to impair T cell function when mutated.”
The results suggest that patients with inborn errors of metabolism may also have immune deficiencies that could impact their treatment, and conversely that metabolic defects may contribute to symptoms in patients with inborn immunodeficiencies.
“There is much more to learn, but these connections could point to different therapies,” said Rathmell, Cornelius Vanderbilt Professor of Immunobiology and director of the Vanderbilt Center for Immunobiology. “Rather than forming distinct categories, these diseases are part of a continuum; there is a gray area between them and a potential new class of inborn errors of immune metabolism that overlaps the two.”
Patterson and the research team used a CRISPR gene editing approach to examine the inborn errors of metabolism genes for immune defects and the inborn errors of immunity genes for metabolism defects. They also analyzed one example from each set—a metabolism gene with an immune defect; an immunity gene with a metabolism defect—to examine the mechanistic effects in more detail.
Overall, Rathmell’s team is interested in understanding how metabolic pathways regulate T cell function with the goal of developing targeted therapies for immune-mediated diseases.
“We have laid the groundwork for further investigation,” said Patterson. “The two examples we have studied in detail point to new biological events and new mechanisms. In addition, we have identified hundreds of other genes whose role in T cell function needs to be analyzed.”
“If you’re trying to understand the links between metabolism and immunity, this is a good starting point,” Rathmell said.
Patterson recently joined the University of Louisville as an assistant professor of biochemistry and molecular genetics. Vanderbilt collaborators Vivian Gama, PhD, associate professor of cell and developmental biology, and Janet Markle, PhD, assistant professor of pathology, microbiology and immunology, made significant contributions to the study.
