Genetic risk factor can lead to hyperinflammatory disorder, death after viral infection

A group of people with fatal H1N1 flu died after their viral infections triggered a deadly hyperinflammatory disorder in susceptible individuals with gene mutations linked to the overactive immune response, according to a study.

Researchers at Cincinnati Children’s Hospital Medical Center, the University of Alabama Birmingham and Children’s of Alabama led the study. They suggest people with other types of infections and identical gene mutations also may be prone to the disorder, known as reactive HLH (rHLH), or haemophagocytic lymphohistiocytosis.

HLH causes the immune system to essentially overwhelm the body with inflammation that attacks vital organs, often leading to death. Study authors raise the possibility of screening children for HLH genes to identify those who may be at risk during a viral infection.

“Viruses that cause robust immune responses may be more likely to trigger rHLH in genetically susceptible people,” said Randy Cron, M.D., Ph.D., a senior investigator on the study and physician in paediatric rheumatology at UAB and Children’s of Alabama. “Prenatal screening for mutations in common HLH-associated genes may find as much as 10 percent of the general population who are at risk for HLH when an inflammation threshold is reached from H1N1 or other infection triggers.”

This study is the first to identify mutations of HLH-associated genes in H1N1 cases where patients had clinical symptoms of rHLH and a related condition called macrophage activation syndrome, or MAS. An outbreak of H1N1 in 2009 turned into a global pandemic. H1N1 has since become part of the viral mix for the annual flu season and preventive vaccine, the authors note. University of Alabama Birmingham