title: IP-10 and MIG are compartmentalized at the site of disease during pleural and meningeal tuberculosis and are decreased after antituberculosis treatment.
abstract: The diagnosis of active tuberculosis (TB) disease remains a challenge, especially in high-burden settings. Cytokines and chemokines are important in the pathogenesis of TB. Here we investigate the usefulness of circulating and compartmentalized cytokines/chemokines for diagnosis of TB. The levels of multiple cytokines/chemokines in plasma, pleural fluid (PF), and cerebrospinal fluid (CSF) were determined by Luminex liquid array-based multiplexed immunoassays. Three of 26 cytokines/chemokines in plasma were significantly different between TB and latent tuberculosis infection (LTBI). Among them, IP-10 and MIG had the highest diagnostic values, with an area under the receiver operating characteristic curve (ROC AUC) of 0.92 for IP-10 and 0.86 for MIG for distinguishing TB from LTBI. However, IP-10 and MIG levels in plasma were not different between TB and non-TB lung disease. In contrast, compartmentalized IP-10 and MIG in the PF and CSF showed promising diagnostic values in discriminating TB and non-TB pleural effusion (AUC = 0.87 for IP-10 and 0.93 for MIG), as well as TB meningitis and non-TB meningitis (AUC = 0.9 for IP-10 and 0.95 for MIG). A longitudinal study showed that the plasma levels of IP-10, MIG, granulocyte colony-stimulating factor (G-CSF), and gamma interferon (IFN-γ) decreased, while the levels of MCP-1/CCL2 and eotaxin-1/CCL11 increased, after successful treatment of TB. Our findings provide a practical methodology for discriminating active TB from LTBI by sequential IFN-γ release assays (IGRAs) and plasma IP-10 testing, while increased IP-10 and MIG at the site of infection (PF or CSF) can be used as a marker for distinguishing pleural effusion and meningitis caused by TB from those of non-TB origins.
authors.affiliation: Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China Guangdong Key Lab of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: Qianting
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China Guangdong Key Lab of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China Guangdong Key Lab of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China Guangdong Key Lab of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China Guangdong Key Lab of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China Guangdong Key Lab of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Luo
authors.affiliation: Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Liu
authors.affiliation: Guangdong Key Lab of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: Boping
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Hardy
authors.initials: H
authors.lastname: Kornfeld
authors.affiliation: Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China Guangdong Key Lab of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China chenxinchun@hotmail.com.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood / Q000378:metabolism*; D054370:Chemokine CXCL9 / Q000097:blood / Q000378:metabolism*; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D055985:Latent Tuberculosis / Q000175:diagnosis; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D014390:Tuberculosis, Meningeal / Q000276:immunology*; D014396:Tuberculosis, Pleural / Q000276:immunology*
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines; D016207:Cytokines