Researchers find weaker immune response to viral infections in children
with mitochondrial disorders
One of the first human studies on how mitochondrial function impacts
immune cells to guide future treatments.

Date:
July 7, 2023
Source:
NIH/National Human Genome Research Institute
Summary:
Researchers found that altered B cell function in children with
mitochondrial disorders led to a weaker and less diverse antibody
response to viral infections. Researchers analyzed gene activity
of immune cells in children with mitochondrial disorders and found
that B cells, which produce antibodies to fight viral infections,
are less able to survive cellular stress.


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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. The
study, published in Frontiers in Immunology was led by researchers at
the National Human Genome Research Institute (NHGRI), who analyzed gene activity of immune cells in children with mitochondrial disorders and
found that B cells, which produce antibodies to fight viral infections,
are less able to survive cellular stress.

"Our work is one of the first examples to study how B cells are affected
in mitochondrial disease by looking at human patients," said Eliza Gordon-Lipkin, M.D., assistant research physician in NHGRI's Metabolism, Infection and Immunity Section and co-first author of the paper.

Mitochondria are important components of nearly every cell in the body
because they convert food and oxygen into energy. Genomic variants in
more than 350 genes have been linked to mitochondrial disorders with
varied symptoms depending on which cells are affected.

"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, head of the Metabolism,
Infection and Immunity Section 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." Around 1 in 5,000 people
worldwide have a mitochondrial disorder. Examples of mitochondrial
disorders are Leigh's syndrome, which primarily affects the nervous
system, and Kearns-Sayre syndrome, which primarily affects the eyes
and heart.

While mitochondrial disorders are known to affect organs such as the
heart, liver, and brain, less is known 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 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," said Dr. McGuire. "But
the B cells are too fragile due to their limited energy, so they are
unable to survive the stressful conditions." 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.

Researchers aim to use the results of this study to guide future treatment
of patients with mitochondrial disorders, noting that more translational studies are needed in this research area.

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========================================================================== Journal Reference:
1. Eliza M. Gordon-Lipkin, Payal Banerjee, Jose Luis Marin Franco,
Tatiana
Tarasenko, Shannon Kruk, Elizabeth Thompson, Derek E. Gildea,
Suiyuan Zhang, Tyra G. Wolfsberg, Willy A. Flegel, Peter
J. McGuire. Primary oxidative phosphorylation defects lead
to perturbations in the human B cell repertoire. Frontiers in
Immunology, 2023; 14 DOI: 10.3389/ fimmu.2023.1142634 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/07/230707111632.htm

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