Characteristics and future prospects of sepsis biomarkers using limulus clotting enzymes

Abstract

 It is widely recognized that an early detection of life-threatening sepsis or septic shock using biomarkers is of great importance for successful treatment of diseases. Bacterial endotoxins in human blood are one of the target analytes to identify sepsis patients. It has been half a century since endotoxin determination techniques with Limulus Amebocyte Lysate (LAL) were applied to human plasma using the gel-clot method. Thereafter, chromogenic and turbidimetric techniques with high specificity to endotoxin or β-D-glucan were successfully developed, and these technologies enable detection of trace amounts of the analytes in blood. With reference to FDA-approved β-D-glucan detection, it became a global standard to aim for early diagnosis of invasive fungal diseases. A number of questions and problems with endotoxin detection, however, still remain unsolved from the standpoint of clinical significance.

 In this review, firstly we focus on development history, recent advances and limitations of LAL techniques coupled with extraction methodologies from blood, and secondly, we suggest a new approach to the solution of the above for biomarker-guided therapy and clinical investigations.