October 2010 Clinical Laboratory News: Diagnostic Profiles

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October 2010: Volume 36, Number 10

Detecting IL-2 and IFN-γ Discriminates Between Active and Latent TB Infection

New research indicates that detecting interleukin-2 (IL-2) in addition to interferon-γ (IFN-γ) discriminates active from latent Mycobacterium tuberculosis infection (Clin Microbiol Infect 2010;16:1282-1284). The research builds on recent studies demonstrating the utility of assays that measure IFN-γ release in blood cells stimulated with M. tuberculosis antigens, according to the authors. IFN-γ release assays accurately diagnose tuberculosis (TB) infection, but do discriminate active from latent TB.

The researchers stimulated whole blood with M. tuberculosis-specific antigens and used the QuantiFERON-TB Gold In Tube test to measure IFN-γ release and a commercially available ELISA assay to measure IL-2 release after 18 and 72 hours of incubation. The specimens came from patients hospitalized in an infectious diseases unit and from control subjects without known exposure to TB. Participants also underwent tuberculin skin testing (TST); those with positive test results and positive M. tuberculosis culture from sputum were considered to have active TB. Latent infection was defined as positive tests in exposed individuals with no signs of active disease.

The investigators found that subjects with either latent or active TB had significantly higher levels of IFN-γ than controls. However, IFN-γ levels between individuals with latent or active TB were not significantly different at 18 or 72 hours after incubation. In contrast, after 72 hours’ incubation, IL-2 levels were significantly higher in patients with latent TB infection than either active TB or healthy controls. The area under the receiver operator characteristic curve was 0.99, and a threshold of 2.0 U/mL yielded a sensitivity of 90% and specificity of 97.5%.

The authors speculate that the increased levels of IL-2 observed in latent TB infection likely reflect more IL-2 secreting and IL-2/IFN-γ-secreting central memory T-cells along with fewer IFN-γ-secreting effector memory T-cells in individuals with latent as opposed to active TB. 

BNP Levels Do Not Predict Intracranial Hemorrhage in Pediatric Trauma Patients

Researchers at Children’s Hospital Los Angeles found that B-type natriuretic peptide (BNP) levels measured during an emergency visit do not predict intracranial hemorrhage (ICH) in pediatric trauma patients (J Trauma 2010;68:1401–5). They conducted the study to determine whether BNP might help identify children most in need of computed tomography (CT) scans. Emerging evidence indicates there is a significantly increased risk of cancer among pediatric patients who have CTs, and protocols to deploy CT more selectively have been implemented. At the same time, emerging evidence suggests that BNP levels are elevated in adults with head injuries. Since BNP tests are readily available and can be performed quickly, the researchers hypothesized that this analyte might predict ICH and help guide physicians in determining whether a CT would be needed.

They enrolled 100 consecutive pediatric patients presenting at the emergency department who were classified as Level I trauma status with the most critical injuries and physiologic parameters. However, of 95 patients who remained in the study for analysis, they did not find a relationship between BNP levels and the presence of various trauma injury measurements such as injury severity score, Glasgow coma scale, or loss of consciousness. In fact, BNP levels for 57.9% of patients were below the assay’s lower limit of detection, and mean BNP levels among patients in the positive ICH group were slightly less than those who were negative for ICH.

While the researchers conclude that based on their study, BNP levels are not clinically relevant to predict CTs with positive results for ICH, they underscored that specimens drawn for the study were taken only upon arrival at the emergency department. However, evidence in adults indicates that BNP levels in aneurysm and subarachnoid hemorrhage did not rise significantly until hours or days later. The authors suggest that further investigation of pediatric BNP levels outside the emergency setting is warranted.

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