title: Is IP-10 an accurate marker for detecting M. tuberculosis-specific response in HIV-infected persons?
abstract: BACKGROUND
  The suboptimal sensitivity of Interferon (IFN)-γ-based in-vitro assays, especially in immunocompromised individuals, emphasizes the need for alternative markers for diagnosing tuberculosis (TB). The objective of this study was to evaluate whether interferon-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-2 and interleukin (IL)-2 can be useful biomarkers for evaluating a specific response to RD1 antigens associated to active TB disease in HIV-infected individuals.
  
  
  RESULTS
  The study was carried out in India, the country with the highest TB burden in the world. Sixty-six HIV-infected individuals were prospectively enrolled, 28 with active-pulmonary-TB and 38 without. The whole blood assay based on RD1-selected peptides (experimental test) and QuantiFERON-TB Gold In tube (QFT-IT) was performed. Plasma was harvested at day-1-post-culture and soluble factors were evaluated by ELISA. The results indicate that by detecting IP-10, the sensitivity of the experimental test and QFT-antigen (75% and 85.7% respectively) for active TB was higher compared to the same assays based on IFN-γ (42.9% and 60.7% respectively) and was not influenced by the ability to respond to the mitogen. By detecting IP-10, the specificity of the experimental test and QFT-antigen (57.9% and 13.2% respectively) for active TB was lower than what was reported for the same assays using IFN-γ-detection (78.9% and 68.4% respectively). On the other side, in vitro IL-2 and MCP-2 responses were not significantly associated with active TB.
  
  
  CONCLUSIONS
  HIV infection does not impair RD1-specific response detected by IP-10, while it significantly decreases IFN-γ-mediated responses. At the moment it is unclear whether higher detection is related to higher sensitivity or lower specificity of the assay. Further studies in high and low TB endemic countries are needed to elucidate this.
authors.affiliation: Translational Research Unit, Department of Epidemiology and Preclinical Research, Lazzaro Spallanzani National Institute for Infectious Diseases (INMI), Rome, Italy. delia.goletti@inmi.it
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
authors.forename: Alamelu
authors.initials: A
authors.lastname: Raja
authors.forename: Basirudeen
authors.initials: B
authors.lastname: Syed Ahamed Kabeer
authors.forename: Camilla
authors.initials: C
authors.lastname: Rodrigues
authors.forename: Archana
authors.initials: A
authors.lastname: Sodha
authors.forename: Stefania
authors.initials: S
authors.lastname: Carrara
authors.forename: Guy
authors.initials: G
authors.lastname: Vernet
authors.forename: Christophe
authors.initials: C
authors.lastname: Longuet
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.forename: Satheesh
authors.initials: S
authors.lastname: Thangaraj
authors.forename: Marc
authors.initials: M
authors.lastname: Leportier
authors.forename: Enrico
authors.initials: E
authors.lastname: Girardi
authors.forename: Philippe Henri
authors.initials: PH
authors.lastname: Lagrange
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000097:blood / Q000175:diagnosis*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D054412:Chemokine CCL8 / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D011446:Prospective Studies; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000209:etiology
chemical_list: D015415:Biomarkers; D054412:Chemokine CCL8; D054357:Chemokine CXCL10; D007376:Interleukin-2