Researchers find weaker immune response to viral infections in children with mitochondrial disorders

Newswise — A recent study conducted by researchers from the National Institutes of Health (NIH) has revealed that children with mitochondrial disorders exhibit impaired B cell function, resulting in a diminished and less diverse antibody response to viral infections. The study, published in Frontiers in Immunology, was spearheaded by scientists at the National Human Genome Research Institute (NHGRI). Through an analysis of immune cell gene activity in affected children, the researchers discovered that B cells, responsible for producing antibodies to combat viral infections, exhibit reduced survival capabilities under cellular stress.

Dr. Eliza Gordon-Lipkin, co-first author of the paper and an assistant research physician in NHGRI's Metabolism, Infection, and Immunity Section, emphasized the significance of their work in investigating the impact of mitochondrial disease on B cells among human patients. This study represents one of the initial endeavors to explore the effects of mitochondrial disorders on B cells, shedding light on the intricate relationship between these diseases and the human immune system.

Mitochondria play a critical role in almost every cell of the body, as they convert food and oxygen into energy. With over 350 genes associated with mitochondrial disorders, the symptoms vary depending on which cells are affected by genomic variants.

According to Peter McGuire, M.B.B.Ch., NHGRI investigator, head of the Metabolism, Infection, and Immunity Section, and senior author of the study, infections pose a severe threat to children with mitochondrial disorders and can even exacerbate the progression of their condition. The team aimed to comprehend the differences in immune cells among these patients and how these variances impact their response to infections.

Mitochondrial disorders affect approximately 1 in 5,000 individuals worldwide. Examples of such disorders include Leigh's syndrome, which primarily affects the nervous system, and Kearns-Sayre syndrome, which primarily affects the eyes and heart.

While the impact of mitochondrial disorders on organs like the heart, liver, and brain is relatively well-known, less is understood about their effects on the immune system.

In this study, researchers employed a genomic technique called single-cell RNA sequencing to examine immune cells present in the blood. These cells encompass various types of white blood cells that aid in combating infections. Under stressful conditions, these cells generate a microRNA known as mir4485. MicroRNAs are short RNA sequences that regulate the activation and deactivation of genes. mir4485 specifically governs cellular pathways crucial for cell survival.

According to Dr. McGuire, it is believed that B cells in patients with mitochondrial disorders experience cellular stress when they transform into plasma cells and generate antibodies. To cope with this stress, these B cells attempt to survive by producing the microRNA. However, due to their limited energy resources, these B cells are inherently fragile and incapable of enduring the challenging conditions.

The researchers employed a technique called VirScan to comprehensively analyze previous viral infections. This assessment allowed them to evaluate the efficacy of the immune system in combating those infections and observe the impact of B cells and plasma cells on antibody production. As a consequence of the weaker antibody response, the immune systems of children with mitochondrial disorders exhibit diminished capabilities in recognizing, neutralizing, and eliminating invading viruses.

The findings of this study aim to provide insights for future treatments of individuals with mitochondrial disorders. The researchers emphasize the need for further translational studies in this research domain to advance our understanding and develop targeted interventions.