Is IP-10 an accurate marker for detecting M. tuberculosis-specific response in HIV-infected persons

Delia Goletti, Alamelu Raja, Basirudeen S. Kabeer, Camilla Rodrigues, Archana Sodha, Stefania Carrara, Guy Vernet, Christophe Longuet, Giuseppe Ippolito, Satheesh Thangaraj, Marc Leportier, Enrico Girardi, Philippe Henri Lagrange

Research output: Contribution to journalArticle

68 Citations (Scopus)

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. Methodology/Principal Findings: 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.

Original languageEnglish
Article numbere12577
Pages (from-to)1-9
Number of pages9
JournalPLoS One
Volume5
Issue number9
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

tuberculosis
Assays
Tuberculosis
Interferons
HIV
Chemokine CCL8
interferons
Proteins
Antigens
proteins
Interleukin-2
assays
Chemokine CXCL10
interleukin-2
antigens
Biomarkers
Mitogens
Gold
Blood
immunocompromised population

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Goletti, D., Raja, A., Kabeer, B. S., Rodrigues, C., Sodha, A., Carrara, S., ... Lagrange, P. H. (2010). Is IP-10 an accurate marker for detecting M. tuberculosis-specific response in HIV-infected persons. PLoS One, 5(9), 1-9. [e12577]. https://doi.org/10.1371/journal.pone.0012577

Is IP-10 an accurate marker for detecting M. tuberculosis-specific response in HIV-infected persons. / Goletti, Delia; Raja, Alamelu; Kabeer, Basirudeen S.; Rodrigues, Camilla; Sodha, Archana; Carrara, Stefania; Vernet, Guy; Longuet, Christophe; Ippolito, Giuseppe; Thangaraj, Satheesh; Leportier, Marc; Girardi, Enrico; Lagrange, Philippe Henri.

In: PLoS One, Vol. 5, No. 9, e12577, 2010, p. 1-9.

Research output: Contribution to journalArticle

Goletti, D, Raja, A, Kabeer, BS, Rodrigues, C, Sodha, A, Carrara, S, Vernet, G, Longuet, C, Ippolito, G, Thangaraj, S, Leportier, M, Girardi, E & Lagrange, PH 2010, 'Is IP-10 an accurate marker for detecting M. tuberculosis-specific response in HIV-infected persons', PLoS One, vol. 5, no. 9, e12577, pp. 1-9. https://doi.org/10.1371/journal.pone.0012577
Goletti, Delia ; Raja, Alamelu ; Kabeer, Basirudeen S. ; Rodrigues, Camilla ; Sodha, Archana ; Carrara, Stefania ; Vernet, Guy ; Longuet, Christophe ; Ippolito, Giuseppe ; Thangaraj, Satheesh ; Leportier, Marc ; Girardi, Enrico ; Lagrange, Philippe Henri. / Is IP-10 an accurate marker for detecting M. tuberculosis-specific response in HIV-infected persons. In: PLoS One. 2010 ; Vol. 5, No. 9. pp. 1-9.
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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. Methodology/Principal Findings: 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.",
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AU - Goletti, Delia

AU - Raja, Alamelu

AU - Kabeer, Basirudeen S.

AU - Rodrigues, Camilla

AU - Sodha, Archana

AU - Carrara, Stefania

AU - Vernet, Guy

AU - Longuet, Christophe

AU - Ippolito, Giuseppe

AU - Thangaraj, Satheesh

AU - Leportier, Marc

AU - Girardi, Enrico

AU - Lagrange, Philippe Henri

PY - 2010

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N2 - 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. Methodology/Principal Findings: 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.

AB - 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. Methodology/Principal Findings: 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.

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