# Leukocyte esterase

Leukocyte esterase (LE) is a type of esterase enzyme released by white blood cells (leukocytes), particularly neutrophils, when they are activated or recruited to a site of infection or inflammation. Although the exact structure and biological function remains unclear, leukocyte esterase represents a type of biomarker for leukocytes and thus can be utilized as a screening or diagnostic tool for various clinical pathologies.

## Structure and function

In a study using cytochemical methods and polyacrylamide gel electrophoresis, nine different esterase isozymes have been identified in human leukocytes with somewhat varying substrate specificities.
Esterase enzymes have the activity of hydrolyzing ester bonds in various substrates. In an electrochemical study using an ester substrate called 4-((tosyl-l-alanyl)oxy)phenyl tosyl-l-alaninate (TAPTA), direct esterolytic activity of leukocyte esterase (LE) could be demonstrated. LE was found to hydrolyze TAPTA, releasing a redox-active fragment that provided a numerical measure of LE activity when oxidized at an electrode.
Studies on the direct immune function of leukocyte esterase activity, however, are unclear. Although leukocyte esterase is released by neutrophils in response to infection, there is limited research on its direct role in the degradation of pathogens or foreign substances during phagocytosis by neutrophils. Instead, leukocyte esterase serves more as an indicator of an immune response, as it reflects the presence of active white blood cells.

## Clinical applications

Leukocyte esterase (LE) can be detected in various bodily fluids such as urine, synovial fluid and ascitic fluid, using reagent strips that are sensitive to LE. The presence of LE is often correlated with the presence of active leukocytes, which can indicate infection or inflammation in those areas. The clinical applications of LE detection include:

### Urinary tract infections (UTI)

A leukocyte esterase test (LE test) is a urine test for the presence of white blood cells and other abnormalities associated with infection.
White blood cells in the urine can indicate a urinary tract infection (UTI). Positive test results may be clinically significant in the right context. The combination of the LE test with the urinary nitrite test provides an excellent screen for establishing the presence of a UTI. Urine test strips (dipsticks) can screen for both. A urine sample that tests positive for both nitrite and leukocyte esterase should be cultured for pathogenic bacteria.

### Spontaneous bacterial peritonitis (SBP)

Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascitic fluid, commonly associated with cirrhosis. The gold standard for diagnosing SBP is an ascitic fluid culture that shows a polymorphonuclear (PMN) cell count of ≥250 cells/mm³. However, leukocyte esterase reagent strips (LERS) show promise as an inexpensive, rapid, non-invasive alternative for detecting the presence of PMNs to diagnose or screen for SBP. A 2021 systematic review and meta-analysis found that LERS demonstrated good overall sensitivity and specificity for diagnosing SBP, although there were some variations depending on the manufacturer.
"It has been proposed that the reagent strip for leukocyte esterase designed for the testing of urine (Combur test UX) could be a useful tool for diagnosing spontaneous bacterial peritonitis (SBP)." Braga et al. concluded that the Combur test UX urine screening test is a very sensitive and specific method for diagnosing SBP in the ascitic fluid of cirrhotic patients who have undergone paracentesis."

### Peri-prosthetic joint infections (PJI)

Leukocyte esterase strip tests also have value in testing for peri-prosthetic joint infections, a potentially devastating complication of joint replacement surgery that can be challenging to diagnose.
In a 2017 systemic review and meta-analysis study, the diagnostic value of leukocyte esterase (LE) testing in synovial fluid for peri-prosthetic joint infections (PJI) was evaluated. The findings suggested that LE had high specificity in excluding PJI. Subsequent 2019 and 2020 meta-analysis studies compared two biomarkers in synovial fluid—alpha-defensin and leukocyte esterase (LE)—to assess their ability to reliably diagnose peri-prosthetic joint infection (PJI). Diagnostic accuracy was measured in terms of sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). The results indicated that both biomarkers demonstrated valuable diagnostic accuracy, with high sensitivity and high specificity. Both are excellent biomarkers for PJI but LE strip testing has the advantage of being much less expensive than alpha-defensin.