Abstract
The functional significance of extracellular Niemann–Pick disease type C2 protein (NPC2) is poorly defined. It is not known whether there is an association between plasma NPC2 and sepsis. Our exploratory, quantitative proteomic analysis showed a significant increase in the level of plasma NPC2 in moribund sepsis patients. Thus, we subsequently determined NPC2 concentration in plasma from healthy subjects, pneumonia patients and sepsis patients with comorbid pneumonia; and analyzed the association of plasma NPC2 with organ dysfunction and prognosis of sepsis patients. Our data shows that plasma NPC2 concentration was significantly higher in pneumonia and sepsis patients than healthy subjects, and was further increased in sepsis patients when the SOFA score reached 14. In addition, NPC2 concentration was significantly higher in patients that subsequently developed septic shock or died within 30 days. Moreover, NPC2 level showed the strongest association with the degree of renal dysfunction in sepsis patients. In moribund sepsis patients, however, NPC2 had highest correlation coefficient with indicators of coagulation anomaly. Based on these results, we conclude that the increase in plasma NPC2 in sepsis patients is associated with multiple organ failure, possibly results from a deficiency in renal clearance, and may serve as a prognostic marker for sepsis.
Highlights
Sepsis is considered as a life-threatening organ dysfunction caused by infection-induced host r esponses1
There was no significant difference in the levels of plasma albumin between these two groups (p = 0.51). These results suggest that the deterioration of organ dysfunction was accompanied by an accumulation of plasma Niemann–Pick disease type C2 protein (NPC2) in these sepsis patients
In NPC1-deficient mice, plasma NPC2 level correlates to its hepatic expression, leading to the suggestion that liver is a major source of circulating NPC211
Summary
Sepsis is considered as a life-threatening organ dysfunction caused by infection-induced host r esponses. Reduced expression of NPC2 is associated with alveolar proteinosis and macrophage accumulation in the lung, liver and spleen, in human as well as rodents, suggesting that NPC2 may play an important role in the pathophysiology of multiple tissues/organs. Reduced expression of NPC2 is associated with alveolar proteinosis and macrophage accumulation in the lung, liver and spleen, in human as well as rodents, suggesting that NPC2 may play an important role in the pathophysiology of multiple tissues/organs6,7 It is not clear whether these pathological effects of NPC2-defficiency reflect a role of intracellular or extracellular NPC2. Understood, but may be involved in the regulation of innate immunity in multiple o rgans7,14 It is currently not known whether extracellular NPC2 is associated with organ dysfunction in sepsis
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