title: CXCL10/IP-10 release is induced by incubation of whole blood from tuberculosis patients with ESAT-6, CFP10 and TB7.7.
abstract: IFN-gamma responses to Mycobacterium tuberculosis specific antigens are used as in vitro diagnostic tests for tuberculosis infection. The tests are sensitive and specific for latent and active tuberculosis disease, but sensitivity may be reduced during immunosuppression. The objective of the study was to explore new ways to improve the diagnosis of tuberculosis infection using CXCL10 and IL-2 as alternative markers to IFN-gamma. CXCL10, IL-2, and IFN-gamma responses to stimulation with ESAT-6/CFP10/TB7.7 were assessed in 12 Quantiferon positive, 8 Quantiferon negative tuberculosis patients and 11 Quantiferon negative controls. CXCL10 and IL-2 were determined by multiplex and IFN-gamma by the Quantiferon ELISA. The median antigen specific CXCL10, IFN-gamma, and IL-2 responses in patients with tuberculosis were 870 pg/ml (range 261-1576 pg/ml), 217 pg/ml (81-1273 pg/ml), 59 pg/ml (14-276 pg/ml) respectively, and the CXCL10 responses were significantly higher than any of the other cytokines measured (p=0.001). In 4/7 individuals with a negative (n=6) or indeterminate (n=1) Quantiferon test, antigen specific CXCL10 responses were detectable at high levels ranging from 196-532 pg/ml. In conclusion CXCL10 was strongly induced after M. tuberculosis specific stimulation and sensitivity appeared superior to the Quantiferon test. Our findings suggest that CXCL10 may serve as an alternative or additional marker for the immunodiagnosis of tuberculosis.
authors.affiliation: Department of Infectious Diseases 144, Copenhagen University Hospital, Kettegaards Alle 30, DK-2650 Hvidovre, Denmark. mruhwald@mail.dk
authors.forename: Morten
authors.initials: M
authors.lastname: Ruhwald
authors.forename: Morten
authors.initials: M
authors.lastname: Bjerregaard-Andersen
authors.forename: Paulo
authors.initials: P
authors.lastname: Rabna
authors.forename: Kristian
authors.initials: K
authors.lastname: Kofoed
authors.forename: Jesper
authors.initials: J
authors.lastname: Eugen-Olsen
authors.forename: Pernille
authors.initials: P
authors.lastname: Ravn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry; D015415:Biomarkers / Q000032:analysis; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D014376:Tuberculosis / Q000097:blood* / Q000175:diagnosis / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; C117940:CFP-10 protein, Mycobacterium tuberculosis; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007376:Interleukin-2; D007371:Interferon-gamma