Elevated growth-arrest-specific protein 6 plasma levels in patients with severe sepsis

Objective: Growth-arrest-specific protein 6 (Gash), an intracellular protein released by apoptotic cells, has been detected in normal plasma. As the Gash system has been implicated in mouse susceptibility to sepsis, and as leukocyte apoptosis is thought to play a major role in the physiopathology of human severe sepsis, we studied Gash plasma levels and possibly related variables in patients with severe sepsis. Design: Matched case-control study. Setting: Adult intensive care unit in a university hospital. Patients: Thirty patients with severe sepsis, 30 patients with organ failure not related to infection, and 30 healthy subjects matched for age and gender. Interventions: Blood draw. Measurements and Main Results: Gash plasma levels were quantified using enzyme-linked immunosorbent assay. Whole-blood gash messenger RNA levels were measured by quantitative real-time polymerase chain reaction. Gash plasma levels were elevated (110 ng/mL [75, 139]; median values [interquartile range]) in severe sepsis patients compared with organ failure patients (85 ng/mL [56, 101]) and healthy subjects (54 ng/mL [49, 68]). In patients with severe sepsis, this increase correlated with the Acute Physiology and Chronic Health Evaluation II severity score, the organ failure Organ Dysfunction and Infection (ODIN) score, and the existence of a septic shock. Gash messenger RNA levels were increased in patients with severe sepsis and correlated specifically with the monocyte count. Conclusions: In severe sepsis, the recently described antiapoptotic protein Gash was found at high levels in plasma and correlated well with the degree of organ dysfunction.