Mycobacterium tuberculosis thymidylate kinase antigen assays for designating incipient, high-risk latent M.tb infection.

Publisher: BioMed Central Country of Publication: England NLM ID: 100968551 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2334 (Electronic) Linking ISSN: 14712334 NLM ISO Abbreviation: BMC Infect Dis Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Disease Progression*; Latent Tuberculosis/*diagnosis ; Mycobacterium tuberculosis/*enzymology ; Nucleoside-Phosphate Kinase/*metabolism ; Tuberculin Test/*methods; Adult ; Antibodies, Bacterial/analysis ; Biomarkers/analysis ; Coinfection ; Female ; HIV Infections/complications ; HIV-1 ; Humans ; Immunoglobulin G/analysis ; Immunoglobulin M/analysis ; Latent Tuberculosis/complications ; Latent Tuberculosis/microbiology ; Male ; Mycobacterium tuberculosis/isolation & purification ; Risk Assessment

Background: Precise designation of high risk forms of latent Mycobacterium tuberculosis-M.tb infections (LTBI) is impossible. Delineation of high-risk LTBI can, however, allow for chemoprophylaxis and curtail majority cases of active tuberculosis (ATB). There is epidemiological evidence to support the view that LTBI in context of HIV-1 co-infection is high-risk for progression to ATB relative to LTBI among HIV-ve persons. We recently showed that assays of M.tb thymidylate kinase (TMKmt) antigen and host specific IgG can differentiate ATB from LTBI and or no TB (NTB, or healthy controls). In this study, we aimed to expose the differential levels of TMKmt Ag among HIV+ve co-infected LTBI relative to HIV-ve LTBI as a strategy to advance these assays for designating incipient LTBI.
Methods: TMKmt host specific IgM and IgG detection Enzyme Immuno-Assays (EIA) were conducted on 40 TB exposed house-hold contacts (22 LTBI vs. 18 no TB (NTB) by QunatiFERON-TB GOLD®); and TMKmt Ag detection EIA done on 82 LTBI (46 HIV+ve vs 36 HIV-ve) and 9 NTB (American donors). Purified recombinant TMKmt protein was used as positive control for the Ag assays.
Results: IgM levels were found to be equally low across QuantiFERON-TB GOLD® prequalified NTB and TB exposed house-hold contacts. Higher TMKmt host specific IgG trends were found among TB house-hold contacts relative to NTB controls. TMKmt Ag levels among HIV+ve LTBI were 0.2676 ± 0.0197 (95% CI: 0.2279 to 0.3073) relative to 0.1069 ± 0.01628 (95% CI: 0.07385 to 0.14) for HIV-ve LTBI (supporting incipient nature of LTBI in context of HIV-1 co-infection). NTB had TMKmt Ag levels of 0.1013 ± 0.02505 (5% CI: 0.0421 to 0.1606) (intimating that some were indeed LTBI).
Conclusions: TMKmt Ag levels represent a novel surrogate biomarker for high-risk LTBI, while host-specific IgG can be used to designate NTB from LTBI.

Lancet. 2011 Jan 8;377(9760):113-4. (PMID: 21226229)
BMC Res Notes. 2017 Aug 8;10 (1):368. (PMID: 28789704)
BMC Microbiol. 2005 Oct 03;5:55. (PMID: 16202138)
PLoS One. 2008 Apr 23;3(4):e1978. (PMID: 18431468)
Microbes Infect. 2003 Feb;5(2):159-67. (PMID: 12650774)
Int J Tuberc Lung Dis. 2008 Feb;12(2):168-73. (PMID: 18230249)
Wkly Epidemiol Rec. 1999 Nov 19;74(46):385-98. (PMID: 10611855)
AIDS. 2006 Aug 1;20(12):1605-12. (PMID: 16868441)
Infection. 2009 Dec;37(6):508-13. (PMID: 19669088)
Trans R Soc Trop Med Hyg. 2005 Dec;99(12):893-900. (PMID: 16139316)
Indian J Chest Dis Allied Sci. 2005 Jan-Mar;47(1):31-7. (PMID: 15704713)
Indian J Exp Biol. 2009 Jun;47(6):447-53. (PMID: 19634710)
BMC Infect Dis. 2005 Jul 28;5:62. (PMID: 16050959)
PLoS Pathog. 2017 Nov 16;13(11):e1006687. (PMID: 29145483)
Lancet Infect Dis. 2004 Dec;4(12):761-76. (PMID: 15567126)
J Infect Dis. 2005 Jan 15;191(2):150-8. (PMID: 15609223)
Nat Rev Immunol. 2005 Oct;5(10):819-26. (PMID: 16200083)
Mycobact Dis. 2017 Jun;7(2):null. (PMID: 28856068)
Tuber Lung Dis. 2000;80(3):131-40. (PMID: 10970761)
Cytokine. 2008 Mar;41(3):307-14. (PMID: 18226915)
Arch Intern Med. 2003 May 12;163(9):1009-21. (PMID: 12742798)
Trends Microbiol. 1995 Mar;3(3):83-5. (PMID: 7773592)
JAMA. 2008 Jul 23;300(4):423-30. (PMID: 18647985)
Indian J Med Microbiol. 2010 Oct-Dec;28(4):281-9. (PMID: 20966555)
Lancet. 2004 Dec 18-31;364(9452):2196-203. (PMID: 15610806)
Am J Respir Crit Care Med. 2007 Mar 1;175(5):514-20. (PMID: 17158278)
Indian J Med Microbiol. 2005 Jul;23(3):151-8. (PMID: 16100419)
Int J Tuberc Lung Dis. 2004 Jun;8(6):792-5. (PMID: 15182152)
PLoS Med. 2007 Jun;4(6):e202. (PMID: 17564490)
JAMA. 2005 Jun 8;293(22):2785-7. (PMID: 15941809)
Curr Opin HIV AIDS. 2009 Jul;4(4):325-33. (PMID: 19532072)
J Lab Clin Med. 2005 Feb;145(2):88-93. (PMID: 15746651)
J Acquir Immune Defic Syndr. 2009 Oct 1;52(2):145-51. (PMID: 19692904)
Int J Tuberc Lung Dis. 2009 Oct;13(10):1253-9. (PMID: 19793430)
PLoS Med. 2011 Aug;8(8):e1001074. (PMID: 21857810)
Lancet. 2016 Jun 4;387(10035):2312-2322. (PMID: 27017310)
Nat Rev Microbiol. 2008 Jul;6(7):520-8. (PMID: 18536727)
Theor Biol Med Model. 2009 Mar 18;6:4. (PMID: 19296833)
Int J Tuberc Lung Dis. 2006 May;10 (5):523-9. (PMID: 16704034)
Clin Infect Dis. 2010 May 15;50 Suppl 3:S201-7. (PMID: 20397949)
Clin Infect Dis. 2000 Jun;30 Suppl 3:S243-6. (PMID: 10875791)
Indian J Med Res. 2011 Dec;134(6):850-65. (PMID: 22310818)
PLoS One. 2011;6(9):e25078. (PMID: 21966416)
PLoS Med. 2008 Jul 22;5(7):e156. (PMID: 18651788)

D43-TW009607-01 International NIH Forgarty; D43 TW009607 United States TW FIC NIH HHS; R24 TW008886 United States TW FIC NIH HHS; N/A International Sida Makerere University; 5R24TW008886 International GF

Keywords: Latent M.tb infections (LTBI);Thymidylate Kinase; Mycobacterium tuberculois; Serodiagnosis; Tuberculosis

0 (Antibodies, Bacterial)
0 (Biomarkers)
0 (Immunoglobulin G)
0 (Immunoglobulin M)
EC 2.7.4.4 (Nucleoside-Phosphate Kinase)
EC 2.7.4.9 (dTMP kinase)

Date Created: 20180318 Date Completed: 20180619 Latest Revision: 20181114

20240628

PMC5857104

10.1186/s12879-018-3007-y

29548281