TY - JOUR
T1 - Antibodies against native proteins of Mycobacterium tuberculosis can detect pulmonary tuberculosis patients
AU - Dewi, Desak Nyoman Surya Suameitria
AU - Mertaniasih, Ni Made
AU - Soedarsono,
AU - Hagino, Kimika
AU - Yamazaki, Tomoya
AU - Ozeki, Yuriko
AU - Artama, Wayan Tunas
AU - Kobayashi, Haruka
AU - Inouchi, Erina
AU - Yoshida, Yutaka
AU - Ishikawa, Satoshi
AU - Shaban, Amina Kaboso
AU - Tateishi, Yoshitaka
AU - Nishiyama, Akihito
AU - Ato, Manabu
AU - Matsumoto, Sohkichi
N1 - Funding Information:
We want to thank all the members of the Department of Bacteriology, Niigata University School of Medicine. We also want to thank the Ministry of Research, Technology, and Higher Education of the Republic of Indonesia. Last but not least, we thank the Director of Soetomo General Academic Hospital, Surabaya, Indonesia, and the Chairman of the Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
Funding Information:
This work was supported by the Research Program on Emerging and Re-emerging Infectious Diseases from AMED under Grant Number JP18fk0108005 and 22fk0108129h0403, MEXT KAKENHI under Grant Number 21KK0136 by MEXT and The United States–Japan Cooperative Medical Science Program against Tuberculosis and Leprosy to Sohkichi Matsumoto. In addition, Grant Number 200/UN3.14/LT/2018 from the Directorate General of Higher Education, the Ministry of Research Technology, and the High Education Republic of Indonesia, also aided this study.
Funding Information:
We want to thank all the members of the Department of Bacteriology, Niigata University School of Medicine. We also want to thank the Ministry of Research, Technology, and Higher Education of the Republic of Indonesia. Last but not least, we thank the Director of Soetomo General Academic Hospital, Surabaya, Indonesia, and the Chairman of the Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - Accurate point-of-care testing (POCT) is critical for managing tuberculosis (TB). However, current antibody-based diagnosis shows low specificity and sensitivity. To find proper antigen candidates for TB diagnosis by antibodies, we assessed IgGs responsiveness to Mycobacterium tuberculosis proteins in pulmonary TB (PTB) patients. We employed major secreted proteins, such as Rv1860, Ag85C, PstS1, Rv2878c, Ag85B, and Rv1926c that were directly purified from M. tuberculosis. In the first screening, we found that IgG levels were significantly elevated in PTB patients only against Rv1860, PstS1, and Ag85B among tested antigens. However, recombinant PstS1 and Ag85B from Escherichia coli (E. coli) couldn’t distinguish PTB patients and healthy controls (HC). Recombinant Rv1860 was not checked due to its little expression. Then, the 59 confirmed PTB patients from Soetomo General Academic Hospital, Surabaya, Indonesia, and 102 HC were tested to Rv1860 and Ag85B only due to the low yield of the PstS1 from M. tuberculosis. The ROC analysis using native Ag85B and Rv1860 showed an acceptable area under curve for diagnosis, which is 0.812 (95% CI 0.734–0.890, p < 0.0001) and 0.821 (95% CI 0.752–0.890, p < 0.0001). This study indicates that taking consideration of native protein structure is key in developing TB’s POCT by antibody-based diagnosis.
AB - Accurate point-of-care testing (POCT) is critical for managing tuberculosis (TB). However, current antibody-based diagnosis shows low specificity and sensitivity. To find proper antigen candidates for TB diagnosis by antibodies, we assessed IgGs responsiveness to Mycobacterium tuberculosis proteins in pulmonary TB (PTB) patients. We employed major secreted proteins, such as Rv1860, Ag85C, PstS1, Rv2878c, Ag85B, and Rv1926c that were directly purified from M. tuberculosis. In the first screening, we found that IgG levels were significantly elevated in PTB patients only against Rv1860, PstS1, and Ag85B among tested antigens. However, recombinant PstS1 and Ag85B from Escherichia coli (E. coli) couldn’t distinguish PTB patients and healthy controls (HC). Recombinant Rv1860 was not checked due to its little expression. Then, the 59 confirmed PTB patients from Soetomo General Academic Hospital, Surabaya, Indonesia, and 102 HC were tested to Rv1860 and Ag85B only due to the low yield of the PstS1 from M. tuberculosis. The ROC analysis using native Ag85B and Rv1860 showed an acceptable area under curve for diagnosis, which is 0.812 (95% CI 0.734–0.890, p < 0.0001) and 0.821 (95% CI 0.752–0.890, p < 0.0001). This study indicates that taking consideration of native protein structure is key in developing TB’s POCT by antibody-based diagnosis.
UR - http://www.scopus.com/inward/record.url?scp=85166598434&partnerID=8YFLogxK
U2 - 10.1038/s41598-023-39436-4
DO - 10.1038/s41598-023-39436-4
M3 - Article
C2 - 37542102
AN - SCOPUS:85166598434
SN - 2045-2322
VL - 13
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 12685
ER -
