A study led by researchers from the National Institutes of Health (NIH) has found that children with mitochondrial disorders exhibit a weaker and less varied immune response to viral infections. This finding, published in Frontiers in Immunology, traces back to the compromised function of B cells, which are crucial in producing antibodies to counteract viral infections. The study stands as one of the earliest to explore the relationship between B cells and mitochondrial disorders in human subjects.
Mitochondria are important for converting food and oxygen into the energy that the body needs to function. Genomic variants in more than 350 genes have been linked to mitochondrial disorders. Symptoms vary depending on which cells are affected. The disorders include Leigh’s syndrome, affecting primarily the nervous system, and Kearns-Sayre syndrome, which mostly impacts the eyes and heart. Worldwide, approximately 1 in 5,000 people have a mitochondrial disorder.
“For children with mitochondrial disorders, infections can be life-threatening or they can worsen the progression of their disorder,” said Peter McGuire, M.B.B.Ch., NHGRI investigator and senior author of the study. “We wanted to understand how immune cells differ in these patients and how that influences their response to infections.”
Notably, mitochondrial disorders have been recognized for affecting various organs like the heart, liver, and brain. However, their impact on the immune system remains relatively understudied.
Leveraging the power of single-cell RNA sequencing—a genomic technique that scrutinizes gene activity in different cell types—the researchers analyzed immune cells in children with mitochondrial disorders. Under stressful conditions, these cells produce a microRNA called mir4485, which regulates cellular pathways essential for cell survival.
“We think that B cells in these patients undergo cellular stress when they turn into plasma cells and produce antibodies, and these B cells then try to survive by producing the microRNA to cope,” explained Dr. McGuire. “But the B cells are too fragile due to their limited energy, so they are unable to survive the stressful conditions.”
The study utilized the VirScan technique to review all past viral infections and gauge the effectiveness of the immune response, specifically examining the role of B cells and plasma cells in antibody production. The findings suggested that due to a weaker antibody response, the immune systems in children with mitochondrial disorders struggle to identify, neutralize, and clear invading viruses and infections.
These novel findings are expected to inform future treatments for patients with mitochondrial disorders. However, researchers note that further translational studies are essential in this emerging field of research.
Mitochondria are important for converting food and oxygen into the energy that the body needs to function. Genomic variants in more than 350 genes have been linked to mitochondrial disorders. Symptoms vary depending on which cells are affected. The disorders include Leigh’s syndrome, affecting primarily the nervous system, and Kearns-Sayre syndrome, which mostly impacts the eyes and heart. Worldwide, approximately 1 in 5,000 people have a mitochondrial disorder.
“For children with mitochondrial disorders, infections can be life-threatening or they can worsen the progression of their disorder,” said Peter McGuire, M.B.B.Ch., NHGRI investigator and senior author of the study. “We wanted to understand how immune cells differ in these patients and how that influences their response to infections.”
Notably, mitochondrial disorders have been recognized for affecting various organs like the heart, liver, and brain. However, their impact on the immune system remains relatively understudied.
Leveraging the power of single-cell RNA sequencing—a genomic technique that scrutinizes gene activity in different cell types—the researchers analyzed immune cells in children with mitochondrial disorders. Under stressful conditions, these cells produce a microRNA called mir4485, which regulates cellular pathways essential for cell survival.
“We think that B cells in these patients undergo cellular stress when they turn into plasma cells and produce antibodies, and these B cells then try to survive by producing the microRNA to cope,” explained Dr. McGuire. “But the B cells are too fragile due to their limited energy, so they are unable to survive the stressful conditions.”
The study utilized the VirScan technique to review all past viral infections and gauge the effectiveness of the immune response, specifically examining the role of B cells and plasma cells in antibody production. The findings suggested that due to a weaker antibody response, the immune systems in children with mitochondrial disorders struggle to identify, neutralize, and clear invading viruses and infections.
These novel findings are expected to inform future treatments for patients with mitochondrial disorders. However, researchers note that further translational studies are essential in this emerging field of research.