A group of researchers have discovered a gene expression pattern that they believe could lead to improved diagnosis and treatment of pediatric septic shock. The study found new evidence linking adverse clinical outcomes with the decreased expression of genes that encode proteins involved in zinc regulation.
The scientists analyzed blood samples from 57 children, which included 15 control patients without septic shock and 42 patients with septic shock, including nine fatal cases.
They found that there were 2,482 differentially regulated gene probes (1,081 upregulated and 1,401 downregulated) between patients with septic shock and controls. Many of the genes downregulated in those with septic shock participate in gene ontologies related to metal or zinc homeostasis.
Comparison of septic shock survivors and nonsurvivors demonstrated differential regulation of 63 gene probes. Among these gene probes, two isoforms of metallothionein (MT) demonstrated increased expression in the nonsurvivors. Consistent with the ability of MT to sequester zinc in the intracellular compartment, nonsurvivors had lower serum zinc levels compared with survivors. In a corroborating study of murine sepsis, MT-null mice demonstrated a survival advantage compared with wild-type mice, report the researchers.
The consortium was composed of 10 medical centers: Cincinnati Children’s, Mott Children’s Hospital at the University of Michigan, Children’s Hospital and Research Center Oakland, Children’s Hospital of Philadelphia, Children’s Mercy Hospital, Penn State Children’s Hospital, University of Virginia Medical Center, Newark Beth Israel Medical Center, The University of Alabama, and DuPont Hospital for Children.
The study is published in the July issue of Physiological Genomics.