title: Cytokine and Antibody Based Diagnostic Algorithms for Sputum Culture-Positive Pulmonary Tuberculosis.
abstract: BACKGROUND
  Tuberculosis (TB) is one of the most serious infectious diseases globally and has high mortality rates. A variety of diagnostic tests are available, yet none are wholly reliable. Serum cytokines, although significantly and frequently induced by different diseases and thus good biomarkers for disease diagnosis and prognosis, are not sufficiently disease-specific. TB-specific antibody detection, on the other hand, has been reported to be highly specific but not sufficiently sensitive. In this study, our aim was to improve the sensitivity and specificity of TB diagnosis by combining detection of TB-related cytokines and TB-specific antibodies in peripheral blood samples.
  
  
  METHODS
  TB-related serum cytokines were screened using a human cytokine array. TB-related cytokines and TB-specific antibodies were detected in parallel with microarray technology. The diagnostic performance of the new protocol for active TB was systematically compared with other traditional methods.
  
  
  RESULTS
  Here, we show that cytokines I-309, IL-8 and MIG are capable of distinguishing patients with active TB from healthy controls, patients with latent TB infection, and those with a range of other pulmonary diseases, and that these cytokines, and their presence alongside antibodies for TB-specific antigens Ag14-16kDa, Ag32kDa, Ag38kDa and Ag85B, are specific markers for active TB. The diagnostic protocol for active TB developed here, which combines the detection of three TB-related cytokines and TB-specific antibodies, is highly sensitive (91.03%), specific (90.77%) and accurate (90.87%).
  
  
  CONCLUSIONS
  Our results show that combining detection of TB-related cytokines and TB-specific antibodies significantly enhances diagnostic accuracy for active TB, providing greater accuracy than conventional diagnostic methods such as interferon gamma release assays (IGRAs), TB antibody Colloidal Gold Assays and microbiological culture, and suggest that this diagnostic protocol has potential for clinical application.
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou, 510630, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou, 510630, China.
authors.forename: Jinfei
authors.initials: J
authors.lastname: Lin
authors.affiliation: Foshan Fourth People's Hospital, Foshan, 528000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute of Biophysics, Chinese Academy of Science, Beijing, 100101, China.
authors.forename: Joy
authors.initials: J
authors.lastname: Fleming
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou, 510630, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Bao'an Chronic Diseases Prevention and Cure Hospital, Shenzhen, 518102, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou, 510630, China.
authors.forename: Haicheng
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou, 510630, China.
authors.forename: Huixin
authors.initials: H
authors.lastname: Guo
authors.affiliation: Foshan Fourth People's Hospital, Foshan, 528000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou, 510630, China.
authors.forename: Xunxun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou, 510630, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou, 510630, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou, 510630, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Guangzhou Chest Hospital, Guangzhou, 510095, China.
authors.forename: Yaoju
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Chinese Medicine Hospital of Huangpu District, Guang zhou, 510700, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Yu
authors.affiliation: Chronic Disease Control and Prevention Station of Dongguan, Guangdong, 523008, China.
authors.forename: Guozhou
authors.initials: G
authors.lastname: Li
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou, 510630, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou, 510630, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Institute of Biophysics, Chinese Academy of Science, Beijing, 100101, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Bi
authors.affiliation: GuangDong Provincial Hospital of Chinese Medicine, GuangDong, 510120, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Guo
authors.affiliation: Bao'an Chronic Diseases Prevention and Cure Hospital, Shenzhen, 518102, China.
authors.forename: Meigui
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D000907:Antibodies, Bacterial / Q000276:immunology*; D015415:Biomarkers; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D059425:Interferon-gamma Release Tests / Q000592:standards; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000379:methods* / Q000592:standards; D013183:Sputum / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G