title: Validation of Mycobacterium tuberculosis Rv1681 protein as a diagnostic marker of active pulmonary tuberculosis.
abstract: The development of an accurate antigen detection assay for the diagnosis of active tuberculosis (TB) would represent a major clinical advance. Here, we demonstrate that the Mycobacterium tuberculosis Rv1681 protein is a biomarker for active TB with potential diagnostic utility. We initially identified, by mass spectroscopy, peptides from the Rv1681 protein in urine specimens from 4 patients with untreated active TB. Rabbit IgG anti-recombinant Rv1681 detected Rv1681 protein in lysates and culture filtrates of M. tuberculosis and immunoprecipitated it from pooled urine specimens from two TB patients. An enzyme-linked immunosorbent assay formatted with these antibodies detected Rv1681 protein in unconcentrated urine specimens from 11/25 (44%) TB patients and 1/21 (4.8%) subjects in whom TB was initially clinically suspected but then ruled out by conventional methods. Rv1681 protein was not detected in urine specimens from 10 subjects with Escherichia coli-positive urine cultures, 26 subjects with confirmed non-TB tropical diseases (11 with schistosomiasis, 5 with Chagas' disease, and 10 with cutaneous leishmaniasis), and 14 healthy subjects. These results provide strong validation of Rv1681 protein as a promising biomarker for TB diagnosis.
authors: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. nira.pollock@childrens.harvard.edu
authors: Nira R
authors: NR
authors: Pollock
authors: Lilia
authors: L
authors: Macovei
authors: Kelly
authors: K
authors: Kanunfre
authors: Rakesh
authors: R
authors: Dhiman
authors: Blanca I
authors: BI
authors: Restrepo
authors: Izelda
authors: I
authors: Zarate
authors: Paula A
authors: PA
authors: Pino
authors: Francisco
authors: F
authors: Mora-Guzman
authors: Ricardo T
authors: RT
authors: Fujiwara
authors: Gerd
authors: G
authors: Michel
authors: Suely S
authors: SS
authors: Kashino
authors: Antonio
authors: A
authors: Campos-Neto
mesh_terms: D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D014355:Chagas Disease / Q000652:urine; D004926:Escherichia coli / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000652:urine; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000652:urine; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D012552:Schistosomiasis / Q000652:urine; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; D007074:Immunoglobulin G; C584456:Rv1681 protein, Mycobacterium tuberculosis
references: Nature. 2009 Nov 26;462(7272):461-4
references: 19940916
references: FEMS Microbiol Rev. 2011 Nov;35(6):1126-57
references: 21521247
references: J Clin Microbiol. 1991 Nov;29(11):2468-72
references: 1774251
references: Clin Exp Immunol. 2008 Jul;153(1):56-62
references: 18460016
references: J Microbiol Methods. 2006 Nov;67(2):220-9
references: 16678925
references: Curr Opin Pulm Med. 2010 May;16(3):262-70
references: 20375787
references: Bull World Health Organ. 2011 May 1;89(5):352-9
references: 21556303
references: Clin Diagn Lab Immunol. 2004 Mar;11(2):280-6
references: 15013976
references: Tuberculosis (Edinb). 2011 Dec;91 Suppl 1:S43-8
references: 22088321
references: Lancet. 2010 May 29;375(9729):1920-37
references: 20488517
references: J Infect Dis. 2012 May 15;205 Suppl 2:S147-58
references: 22496353
references: Clin Vaccine Immunol. 2008 Apr;15(4):638-43
references: 18305107
references: Expert Rev Anti Infect Ther. 2007 Jun;5(3):327-31
references: 17547496
references: PLoS One. 2010 Mar 24;5(3):e9848
references: 20352098
references: Biochem J. 1971 Dec;125(3):781-91
references: 5145899
references: J Immunol. 2005 Oct 15;175(8):5298-305
references: 16210635
references: Nature. 2006 Nov 23;444 Suppl 1:49-57
references: 17159894
references: J Immunol Methods. 1992 Jun 24;150(1-2):23-32
references: 1613256
references: BMC Infect Dis. 2012 Apr 26;12:103
references: 22536883
references: Lancet Infect Dis. 2006 Oct;6(10):664-74
references: 17008175
references: J Infect Dis. 2011 Nov 15;204 Suppl 4:S1196-202
references: 21996702