title: IP-10 response to RD1 antigens might be a useful biomarker for monitoring tuberculosis therapy.
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.
authors: Department of Immunology, Tuberculosis Research Centre (ICMR), Tamil Nadu, Chennai, India.
authors: Basirudeen Syed Ahamed
authors: BS
authors: Kabeer
authors: Alamelu
authors: A
authors: Raja
authors: Balambal
authors: B
authors: Raman
authors: Satheesh
authors: S
authors: Thangaraj
authors: Marc
authors: M
authors: Leportier
authors: Giuseppe
authors: G
authors: Ippolito
authors: Enrico
authors: E
authors: Girardi
authors: Philippe Henri
authors: PH
authors: Lagrange
authors: Delia
authors: D
authors: Goletti
references: J Infect Dis. 2006 Feb 1;193(3):354-9
references: 16388482
references: Clin Diagn Lab Immunol. 2005 Nov;12(11):1311-6
references: 16275946
references: BMC Infect Dis. 2010 Nov 22;10:333
references: 21092156
references: BMC Res Notes. 2009 Feb 04;2:19
references: 19193208
references: BMC Infect Dis. 2006 Mar 30;6:66
references: 16573826
references: J Infect Dis. 2006 Oct 1;194(7):984-92
references: 16960787
references: PLoS One. 2010 Sep 07;5(9):e12577
references: 20830287
references: PLoS One. 2008;3(10):e3417
references: 18923709
references: Int J Tuberc Lung Dis. 2009 Jun;13(6):731-6
references: 19460249
references: Infect Immun. 1996 Jan;64(1):16-22
references: 8557334
references: Respirology. 2008 May;13(3):468-72
references: 18399875
references: Eur Respir J. 2008 Dec;32(6):1607-15
references: 18684849
references: Am J Respir Crit Care Med. 2006 Aug 1;174(3):349-55
references: 16690977
references: PLoS One. 2010 Feb 04;5(2):e9051
references: 20140219
references: J Infect Dis. 1997 May;175(5):1251-4
references: 9129098
references: J Infect. 2010 Jul;61(2):133-43
references: 20470822
references: BMC Infect Dis. 2010 May 27;10:138
references: 20507549
references: J Infect. 2009 Mar;58(3):197-204
references: 18848730
references: Curr Opin Pulm Med. 2009 May;15(3):188-200
references: 19387262
references: Microbes Infect. 2007 Jun;9(7):806-12
references: 17533146
references: PLoS One. 2008;3(12):e3901
references: 19065267
references: Br Med Bull. 2010;93:69-84
references: 19926636
references: Diagn Microbiol Infect Dis. 2009 Jan;63(1):43-51
references: 19026511
references: Microbes Infect. 2005 Jan;7(1):1-8
references: 15716076
references: Infection. 2007 Apr;35(2):98-103
references: 17401714
references: BMC Infect Dis. 2008 Jan 28;8:11
references: 18226199
references: Respir Res. 2007 Jan 27;8:5
references: 17257436
references: Ann Intern Med. 2008 Aug 5;149(3):177-84
references: 18593687
references: MMWR Recomm Rep. 2010 Jun 25;59(RR-5):1-25
references: 20577159
references: Respir Med. 2009 Jan;103(1):30-4
references: 18977647
references: Respirology. 2010 Feb;15(2):220-40
references: 20199641
references: J Immunol. 2003 Feb 15;170(4):2046-52
references: 12574375
references: Am J Respir Crit Care Med. 2007 Feb 1;175(3):282-7
references: 17082492
references: Clin Diagn Lab Immunol. 1999 Sep;6(5):675-82
references: 10473516
references: AIDS. 2010 Jan 16;24(2):323-5
references: 20010069
references: Mol Med. 2003 Mar-Apr;9(3-4):105-11
references: 12865946
references: Int J Tuberc Lung Dis. 2008 Oct;12(10):1146-52
references: 18812044
references: Am J Respir Crit Care Med. 2004 Jul 1;170(1):59-64
references: 15059788
references: Indian J Pediatr. 2004 Dec;71(12):1063-8
references: 15630312
references: PLoS One. 2009;4(4):e5187
references: 19365543
references: J Bacteriol. 1996 Mar;178(5):1274-82
references: 8631702
references: Indian J Med Res. 2006 Oct;124(4):439-42
references: 17159265
references: Eur Respir J. 2010 Dec;36(6):1488-90
references: 21119209
references: J Immunol. 2001 Nov 1;167(9):5217-25
references: 11673535
references: Clin Infect Dis. 2005 May 1;40(9):1301-8
references: 15825033
references: Clin Infect Dis. 2004 Mar 1;38(5):754-6
references: 14986262