Understanding genes involved with weakened immunity during sepsis in kids

When a child's immune system overreacts to an infection during sepsis, it can have a damaging effect on their small body.

To protect itself from this overreaction, the body attempts to taper down the overwhelming immune reaction by weakening the immune system – but sometimes it may overly weaken the immune system.

Now, Michigan Medicine researchers are trying to better understand how a child develops this form of profoundly weakened immunity during sepsis, known as immunoparalysis, which is associated with increased morbidity and mortality.

"This phenomenon significantly dampens the immune system and is associated with poor outcomes in children, but how and why this happens is still unclear," said lead author Mohamed Farhat, M.D., a pediatric critical care physician at University of Michigan Health C.S. Mott Children's Hospital and researcher at Michigan Medicine.

"We are trying to better understand what changes are happening to the immune system when children go through sepsis, which is a leading cause of mortality. We are hoping that this information will eventually allow us to manage sepsis in a different way: adopting more precise approaches to diagnosis and treatment in the future."    

In the pilot study, the Michigan research team examined 26 children who had sepsis, severe sepsis or septic shock and were admitted to the pediatric intensive care unit.

Children were divided into two groups – one group who were immunoparalyzed (had weakened immunity) and a group that were not. Researchers compared groups to learn what genes are turned on and off during immunoparalysis.

Researchers identified several genes that are expressed differently between children who experienced immunoparalysis and those who didn't, for the first time linking these genes specifically to the phenomenon, according to the findings in Pediatric Critical Care Medicine.

Researchers plan to validate the study in a larger group of children with severe sepsis or septic shock. Further studies are also needed to identify more genes, proteins, and mechanisms involved with this phenomenon.

"We need more studies to gain enough knowledge, which would later allow us to test therapies that target certain genes or proteins involved in this condition that can potentially reverse it and improve outcomes in these kids," Farhat said.

Mary Dahmer, Ph.D., associate professor of pediatrics at the U-M Medical School, was the senior author of this study. Other authors include Jeffrey Shadley, Ph.D.; Nadine Halligan M.S.; Antonia Popova, M.D., and Michael Quasney, M.D., Ph.D., all of U-M, and Mark Hall, M.D., of Nationwide Children's Hospital.

Study cited: "Differences in the Genomic Profiles of Immunoparalyzed and Nonimmunoparalyzed Children With Sepsis: A Pilot Study," Pediatric Critical Care Medicine. DOI: 10.1097/PCC.0000000000002860