Children with mitochondrial disorders show weaker immune response to viral infections

In a new study, National Institutes of Health (NIH) researchers found that altered B cell function in children with mitochondrial disorders led to a weaker and less diverse antibody response to viral infections. While mitochondrial disorders are known to affect organs such as the heart, liver, and brain, less is known about how they affect the immune system.

Using a genomic technique called single-cell RNA sequencing, which analyzes gene activity in different cell types, researchers studied immune cells found in the blood. These cells include different types of white blood cells that help the body fight infections. During stressful conditions, these cells produce a microRNA called mir4485. MicroRNAs are small strings of RNA that help control when and where genes are turned on and off. mir4485 controls cellular pathways that help cells survive.

“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. But the B cells are too fragile due to their limited energy, so they are unable to survive the stressful conditions,” said Dr. McGuire.

Researchers used a technique called VirScan to look at all past viral infections, assess how well the immune system fought those infections, and see the effects of B cells and plasma cells on antibody production. With a weaker antibody response, the immune systems in children with mitochondrial disorders are less able to recognize and neutralize invading viruses and clear infections.

Reference: Primary oxidative phosphorylation defects lead to perturbations in the human B cell repertoire, Frontiers in Immunology, DOI 10.3389/fimmu.2023.1142634