A Blood Test for Susceptibility to Septic Shock?
Abstract & Commentary
Synopsis: TNF2, a specific polymorphism within the tumor necrosis factor-alpha gene promoter, was found more often in the blood of patients with septic shock than in healthy blood donors. Patients with the TNF2 allele were 3.7 times more likely to die than patients without this finding.
Source: Mira JP, et al. JAMA 1999;282(6):561-568.
The cytokine tumor necrosis factor-alpha (TNF-a) is believed to be involved in the pathogenesis of septic shock. A polymorphism within the TNF-a gene promoter called TNF2 has been shown to be associated with enhanced TNF-a production and also with worse clinical outcomes in certain types of severe infections. This multicenter European study sought to determine the frequency with which the TNF2 allele was present in the blood of patients with clinical septic shock, and also whether it was associated with mortality.
Blood was drawn from 89 patients with septic shock and also from 89 healthy unrelated blood donors. The investigators determined the frequency of the TNF2 allele and also the levels of TNF-a in the blood, and correlated these findings with the patients’ clinical outcomes. All the patients required mechanical ventilation, and 54% of them died. The polymorphism frequencies of the controls and the patients with septic shock differed significantly at only one allele—TNF2 (18% vs 39%; P = 0.002). The frequency of the TNF2 allele was 52% among septic shock patients who subsequently died, as compared to 24% among those who survived (P = 0.008). The concentrations of TNF-a in the blood of patients with the TNF2 allele vs. a comparison allele were not statistically different. By multiple logistic regression analysis of the data after controlling for age and the probability of death by SAPS II score, patients with the TNF2 allele were 3.7 times as likely to die than patients lacking the allele (95% confidence interval, 1.37-10.24-fold increased risk of death).
COMMENT BY DAVID J. PIERSON, MD, FACP, FCCP
This study showed an increased frequency of a particular identifiable genetic polymorphism, TNF2, in patients with septic shock. Further, it found that, among patients with septic shock, those with the allele in question were 3.7 times more likely to die than those without it. Although testing for TNF2 is not clinically available, and would be unlikely to help in the management of an individual patient at this point, this study raises some exciting possibilities. One is that it may one day be possible to develop specific therapies to prevent or counteract the effects of the TNF2 allele, modifying the individual’s susceptibility to and clinical manifestations of septic shock. Another, admittedly remote, possibility is that, as genetic testing becomes more practical and encompasses ever larger portions of the human genome, we may be able assemble a genetic profile on an individual at birth that could be used to identify susceptibilities and tailor therapies to a variety of diseases throughout that person’s life.
Tumor necrosis factor-a is:
a. an antibody that blunts the body’s response to infection.
b. a facilitator of phagocytosis by neutrophils that helps to control infection.
c. a cytokine believed to be involved in the pathogenesis of septic shock.
d. a new, genetically engineered vaccine against septic shock.
e. a naturally occurring antibacterial agent found in malignant tumors.
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