Evaluation of circulating serum cathelicidin levels as a potential biomarker to discriminate between active and latent tuberculosis in Uganda

Abstract

Background Tuberculosis remains a major public health problem worldwide accounting for 1.4 million deaths annually. LL-37 is an effector molecule involved in immunity with both antimicrobial and immunomodulatory properties. The purpose of this study was to compare LL-37 circulatory levels among participants with active and latent tuberculosis and to determine its ability to discriminate between the two infectious states. Methods A cross-sectional study was performed among 56 active tuberculosis patients, 49 latent tuberculosis individuals, and 43 individuals without tuberculosis infection. The enzyme-linked immunosorbent assay was used to assess LL-37 levels. Data analysis was performed using STATA software and Graph pad Prism version 8. Mann-Whitney U test was used for correlation between variables with two categories and the Kruskal-Wallis test for three or more categories. Results The study had more female participants than males, with similar median ages across the three groups, 29.5, 25.0, and 23.0 years respectively. Active tuberculosis patients had significantly higher LL-37 levels compared to those with latent tuberculosis and without tuberculosis. The median/interquartile ranges were 318.8 ng/ml (157.9–547.1), 242.2 ng/ml (136.2–579.3), 170.9 ng/ml (129.3–228.3); p = 0.002 respectively. Higher LL-37 was found in the male participant with median/interquartile range, 424.8 ng/ml (226.2–666.8) compared to the females 237.7 ng/ml (129.6–466.6); p = 0.045. LL-37 had better discriminatory potential between active tuberculosis and no tuberculosis (AUC = 0.71, sensitivity 71.4% specificity = 69.8%) than with latent tuberculosis (AUC = 0.55, sensitivity = 71.4%, specificity = 44.9%). There was moderate differentiation between latent tuberculosis and no tuberculosis (AUC = 0.63, sensitivity = 44.9% specificity = 90.7%). Conclusion Significantly higher LL-37 levels were observed among active tuberculosis patients than those without tuberculosis infection and were, therefore able to discriminate between active tuberculosis and other tuberculosis infectious states, especially with no tuberculosis. Further assessment of this biomarker as a screening tool to exclude tuberculosis is required.

Comparison of frailty in patients with nontuberculous mycobacterial lung disease and bronchiectasis: a prospective cohort study

“…Although not NTM disease, it has been reported, for example, that in leprae infections, serum hCAP/LL-37 is lower in the leprosy group than in healthy individuals, and even lower in the untreated group (more early infection) than in the treated group [ 31 ]. However, previous reports in patients with tuberculosis have shown a positive correlation between systemic hCAP/LL-37 secretion and disease severity, [ 32 ] so it is still susceptible to fluctuations depending on the progression of the disease, type of strains and the timing of blood sampling. The concentration of hCAP/LL-37 probably differs in the early, middle and long-term stages of infection, so the stage at which blood samples are taken is also an important factor.…”

A Comparison of Cathelicidin Levels in the Skin of Leprosy Patients and Their Household Contacts

“…In leprosy patients, the primary site of infection is in the skin, so the level of cathelicidin in infected skin scrapings represents the patient’s infection status ( 26 ). Other studies state that cathelicidin levels are identical to bacterial load or how many microorganisms there are in the body ( 27 , 28 ). The more bacteria or microorganisms in the body, the higher the production of cathelicidin ( 28 , 29 ).…”

“…Other studies state that cathelicidin levels are identical to bacterial load or how many microorganisms there are in the body ( 27 , 28 ). The more bacteria or microorganisms in the body, the higher the production of cathelicidin ( 28 , 29 ). This can explain why cathelicidin levels in the HC group are lower compared to leprosy patients.…”

Correlation Between Vitamin D Levels on Pregnant Women With Latent Tuberculosis Infection and Vitamin D Levels, Cathelicidin, Interferon γ, and Tlr2 Expression on Neonates in Medan, North Sumatera, Indonesia

“…This result is in accordance with prior researches where the increase of cathelicidin on the airway tract cells (trachea) on newborns with acute respiratory infection will established its function as one of the immune defense systems against respiratory infections, and TB infections. 35,36,37 Interferon γ is a strong cytokine response on neonates that plays a role in lowering the incidence of respiratory infections 9 and is an early cytokine response when infected with M. tuberculosis. The increase of cathelicidin and IFNγ levels on newborns happened because the newborn could have been exposed to bacteria during the delivery process.…”