MSGID: 1:317/3 64a8e69f   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/07/230707111632.htm   
      
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