Serum inflammatory profiles in pulmonary tuberculosis and their association with treatment response.
The aim of this study was to evaluate serum cytokines and natural antimicrobial peptide profiles in pulmonary tuberculosis, and compare them with levels in controls without tuberculosis, to explore the associations between these biomarkers and response to antituberculosis treatment. Serum levels of 10 biomarkers were measured using a Luminex bead array platform. Tuberculosis biosignatures were identified from the discovery cohort (n=148) and were validated in the independent cohort (n=148). Association between biosignatures and clinical outcome was investigated with negative conversion in follow-up sputum culture after 2months of treatment. Serum concentrations of eotaxin, MIP-1α, sIL-2Rα, and lipocalin 2 were significantly different between pulmonary tuberculosis patients and controls (P<0.05). Serum concentrations of eotaxin and sIL-2Rα were higher in pulmonary tuberculosis patients than in controls, while those of MIP-1α and lipocalin 2 were lower (P<0.05). Eotaxin concentrations were significantly higher in good responders to treatment (P<0.05), indicating this immunomolecule may serve as a positive predictor for therapy response in pulmonary tuberculosis. The magnitude serum eotaxin, MIP-1α, sIL-2Rα, and lipocalin 2 are important indicators for pulmonary tuberculosis. These biomarkers alone or combinatorial detections have potential applicability in monitoring tuberculosis patients during antituberculosis treatment.



Cytokines and endogenous antimicrobial peptides represent an important part of immune system and the identification of a pattern of differentially expressed those biomarkers (a "biosignature") could help to differentiate tuberculosis infection from the non-infected state which might eventually assist case identification and accelerate access to treatment. In this direction, cytokine analysis including multiple serum biomarkers to evaluate biosignatures of pulmonary tuberculosis would provide basic knowledge to aid understanding of the pathophysiology of tuberculosis infection and for the development of future diagnostic methods, treatments, and monitoring for pulmonary tuberculosis.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: rihwa.choi@samsung.com.
Rihwa
R
Choi
Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, Republic of Korea. Electronic address: kyunga.j.kim@samsung.com.
Kyunga
K
Kim
Biostatistics Team, Samsung Biomedical Research Institute, Seoul, Republic of Korea. Electronic address: minji93.kim@samsung.com.
Min-Ji
MJ
Kim
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: suyoung5505@hanmail.net.
Su-Young
SY
Kim
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: ojung.kwon@samsung.com.
O Jung
OJ
Kwon
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: kyeongman.jeon@samsung.com.
Kyeongman
K
Jeon
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: kerrybe.park@samsung.com.
Hye Yun
HY
Park
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: bh82.jeong@samsung.com.
Byeong-Ho
BH
Jeong
Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: sjshin@yuhs.ac.
Sung Jae
SJ
Shin
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: wjkoh@skku.edu.
Won-Jung
WJ
Koh
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: sy117.lee@samsung.com.
Soo-Youn
SY
Lee
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D054405:Chemokine CCL3 / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000031:analogs & derivatives / Q000097:blood; D000071068:Lipocalin-2 / Q000097:blood; D008297:Male; D008875:Middle Aged; D013183:Sputum / Q000737:chemistry / Q000382:microbiology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D055815:Young Adult
D000995:Antitubercular Agents; D015415:Biomarkers; D054405:Chemokine CCL3; D016207:Cytokines; D007376:Interleukin-2; D000071068:Lipocalin-2; C067246:interleukin-2, succinyl-
Antituberculosis treatment; Biomarker; Immunomolecule; Serum; Tuberculosis