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Open Access Research article

IP-10 response to RD1 antigens might be a useful biomarker for monitoring tuberculosis therapy

Basirudeen Syed Ahamed Kabeer1, Alamelu Raja1, Balambal Raman2, Satheesh Thangaraj3, Marc Leportier3, Giuseppe Ippolito4, Enrico Girardi5, Philippe Henri Lagrange6 and Delia Goletti7*

Author Affiliations

1 Department of Immunology, Tuberculosis Research Centre (ICMR), Tamil Nadu, Chennai, India

2 Department of Clinical Research, Tuberculosis Research Centre (ICMR), Mayor V.R. Ramanathan Road, Chetpet, Chennai -- 600 031, Tamil Nadu, India

3 Biomérieux, Research & Development Immunoassays, Chemin de l'Orme, Marcy L'Etoile, France

4 Scientific Direction, Lazzaro Spallanzani National Institute for Infectious Diseases (INMI), Rome, Italy

5 Department of Epidemiology and Preclinical Research, INMI, Rome, Italy

6 Microbiology Service, Saint Louis Hospital, Paris, France

7 Translational Research Unit, Department of Epidemiology and Preclinical Research, (INMI), Rome, Italy

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BMC Infectious Diseases 2011, 11:135  doi:10.1186/1471-2334-11-135

Published: 19 May 2011

Abstract

Background

There is an urgent need of prognosis markers for tuberculosis (TB) to improve treatment strategies. The results of several studies show that the Interferon (IFN)-γ-specific response to the TB antigens of the QuantiFERON TB Gold (QFT-IT antigens) decreases after successful TB therapy. The objective of this study was to evaluate whether there are factors other than IFN-γ [such as IFN-γ inducible protein (IP)-10 which has also been associated with TB] in response to QFT-IT antigens that can be used as biomarkers for monitoring TB treatment.

Methods

In this exploratory study we assessed the changes in IP-10 secretion in response to QFT-IT antigens and RD1 peptides selected by computational analysis in 17 patients with active TB at the time of diagnosis and after 6 months of treatment. The IFN-γ response to QFT-IT antigens and RD1 selected peptides was evaluated as a control. A non-parametric Wilcoxon signed-rank test for paired comparisons was used to compare the continuous variables at the time of diagnosis and at therapy completion. A Chi-square test was used to compare proportions.

Results

We did not observe significant IP-10 changes in whole blood from either NIL or QFT-IT antigen tubes, after 1-day stimulation, between baseline and therapy completion (p = 0.08 and p = 0.7 respectively). Conversely, the level of IP-10 release to RD1 selected peptides was significantly different (p = 0.006). Similar results were obtained when we detected the IFN-γ in response to the QFT-IT antigens (p = 0.06) and RD1 selected peptides (p = 0.0003). The proportion of the IP-10 responders to the QFT-IT antigens did not significantly change between baseline and therapy completion (p = 0.6), whereas it significantly changed in response to RD1 selected peptides (p = 0.002). The proportion of IFN-γ responders between baseline and therapy completion was not significant for QFT-IT antigens (p = 0.2), whereas it was significant for the RD1 selected peptides (p = 0.002), confirming previous observations.

Conclusions

Our preliminary study provides an interesting hypothesis: IP-10 response to RD1 selected peptides (similar to IFN-γ) might be a useful biomarker for monitoring therapy efficacy in patients with active TB. However, further studies in larger cohorts are needed to confirm the consistency of these study results.