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

被引:4
作者
Acen, Ester Lilian [1 ]
Kateete, David Patrick [2 ]
Worodria, William [3 ]
Olum, Ronald [4 ]
Joloba, Moses L. [2 ]
Bbuye, Mudarshiru [4 ,5 ]
Biraro, Irene Andia [6 ,7 ]
机构
[1] Makerere Univ, Sch Biomed Sci, Dept Physiol, Coll Hlth Sci, Kampala, Uganda
[2] Makerere Univ, Sch Biomed Sci, Dept Immunol & Mol Biol, Coll Hlth Sci, Kampala, Uganda
[3] Mulago Natl Referral Hosp, Div Pulm, Dept Med, Kampala, Uganda
[4] Makerere Univ, Sch Med, Dept Med, Coll Hlth Sci Unit, Kampala, Uganda
[5] Makerere Univ, Makerere Lung Inst Coll Hlth Sci, Kampala, Uganda
[6] Uganda Virus Res Inst, Med Res Council, Entebbe, Uganda
[7] London Sch Hyg & Trop Med Uganda, Res Unit, Entebbe, Uganda
基金
美国国家卫生研究院; 英国惠康基金;
关键词
VITAMIN-D; ANTIMICROBIAL PEPTIDES; LL-37; EXPRESSION; DEFENSINS; INFECTION; PROTEINS; ROLES; CELLS; TNF;
D O I
10.1371/journal.pone.0272788
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:19
相关论文
共 52 条
[41]   Role of C-Reactive Protein at Sites of Inflammation and Infection [J].
Sproston, Nicola R. ;
Ashworth, Jason J. .
FRONTIERS IN IMMUNOLOGY, 2018, 9
[42]   Circulating Cathelicidin Concentrations in a Cohort of Healthy Children: Influence of Age, Body Composition, Gender and Vitamin D Status [J].
Stukes, Taylor M. ;
Shary, Judith R. ;
Wei, Wei ;
Ebeling, Myla D. ;
Dezsi, Kaleena B. ;
Shary, Frank S. ;
Forestieri, Nina E. ;
Hollis, Bruce W. ;
Wagner, Carol L. .
PLOS ONE, 2016, 11 (05)
[43]   A bioinformatics analysis to identify novel biomarkers for prognosis of pulmonary tuberculosis [J].
Sun, Yahong ;
Chen, Gang ;
Liu, Zhihao ;
Yu, Lina ;
Shang, Yan .
BMC PULMONARY MEDICINE, 2020, 20 (01)
[44]   Innate immunity to Mycobacterium tuberculosis [J].
van Crevel, R ;
Ottenhoff, THM ;
van der Meer, JWM .
CLINICAL MICROBIOLOGY REVIEWS, 2002, 15 (02) :294-+
[45]   Structures of Human Host Defense Cathelicidin LL-37 and Its Smallest Antimicrobial Peptide KR-12 in Lipid Micelles [J].
Wang, Guangshun .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (47) :32637-32643
[46]   The human cathelicidin LL-37 A pore-forming antibacterial peptide and host-cell modulator [J].
Xhindoli, Daniela ;
Pacor, Sabrina ;
Benincasa, Monica ;
Scocchi, Marco ;
Gennaro, Renato ;
Tossi, Alessandro .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2016, 1858 (03) :546-566
[47]   Vitamin D status and antimicrobial peptide cathelicidin (LL-37) concentrations in patients with active pulmonary tuberculosis [J].
Yamshchikov, Alexandra V. ;
Kurbatova, Ekaterina V. ;
Kumari, Meena ;
Blumberg, Henry M. ;
Ziegler, Thomas R. ;
Ray, Susan M. ;
Tangpricha, Vin .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 2010, 92 (03) :603-611
[48]   Significance of LL-37 on Immunomodulation and Disease Outcome [J].
Yang, Binbin ;
Good, David ;
Mosaiab, Tamim ;
Liu, Wei ;
Ni, Guoying ;
Kaur, Jasmine ;
Liu, Xiaosong ;
Jessop, Calvin ;
Yang, Lu ;
Fadhil, Rushdi ;
Yi, Zhengjun ;
Wei, Ming Q. .
BIOMED RESEARCH INTERNATIONAL, 2020, 2020
[49]   Association of Body Mass Index With Tuberculosis Mortality A Population-Based Follow-Up Study [J].
Yen, Yung-Feng ;
Chuang, Pei-Hung ;
Yen, Muh-Yong ;
Lin, Shu-Yi ;
Chuang, Peing ;
Yuan, Mei-Jen ;
Ho, Bo-Lung ;
Chou, Pesus ;
Deng, Chung-Yeh .
MEDICINE, 2016, 95 (01)
[50]   The role of cathelicidins in the innate host defenses of mammals [J].
Zanetti, M .
CURRENT ISSUES IN MOLECULAR BIOLOGY, 2005, 7 :179-196