Children with mitochondrial disorders have weaker immune response to infection

Key takeaways:

• A newly published study is one of the first to examine how mitochondrial function impacts humans’ immune response to infection.
• The findings will guide future treatment, according to researchers.

Children with mitochondrial disorders have altered B cell function, which weakens their immune response to viral infections, according to study results published in Frontiers in Immunology.

“Our work is one of the first examples to study how B cells are affected in mitochondrial disease by looking at human patients,” Eliza Gordon-Lipkin, MD, an assistant research physician in the section of metabolism, infection and immunity at the National Human Genome Research Institute (NHGRI), said in a press release issued by the NIH.

Although about one in 5,000 people worldwide have a mitochondrial disorder — such as Leigh syndrome or Kearns-Sayre syndrome — most studies on this topic have been conducted using mice.

“There are many recognized differences between mouse and human immunology,” Gordon-Lipkin and colleagues wrote. “Therefore, including humans as the ‘highest order experimental system’ is an imperative for translational immunometabolism studies.”

“For children with mitochondrial disorders, infections can be life threatening or they can worsen the progression of their disorder,” Peter McGuire, MBBCh, head of the NHGRI’s Metabolism, Infection and Immunity Section, said in the release. “We wanted to understand how immune cells differ in these patients and how that influences their response to infections.”

Researchers at the institute examined blood from eight children with mitochondrial disorders via single-cell RNA sequencing, which finds gene activity in different cell types, most notably in the blood.

They found that their B cells — which are crucial for producing antibodies against viruses — were less likely to survive cellular stress.

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

The researchers said they intend to use the results to guide future treatment.

References:

Gordon-Lipkin E, et al. Front Immunol. 2023;doi:10.3389/fimmu.2023.1142634.

Researchers find weaker immune response to viral infections in children with mitochondrial disorders. https://www.nih.gov/news-events/news-releases/researchers-find-weaker-immune-response-viral-infections-children-mitochondrial-disorders. Published July 7, 2023. Accessed July 7, 2023.