Biomarkers for Clinical and Incipient Tuberculosis: Performance in a TB-endemic Country

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2008 May 1

PMID 18446210

Citations 19

Authors

Ajay Wanchu

Yuxin Dong

Sunil Sethi

V P Myneedu

Arthur Nadas

Zhentong Liu

John Belisle

Suman Laal

Affiliations

Soon will be listed here.

Abstract

Background: Simple biomarkers are required to identify TB in both HIV(-)TB(+) and HIV(+)TB(+) patients. Earlier studies have identified the M. tuberculosis Malate Synthase (MS) and MPT51 as immunodominant antigens in TB patients. One goal of these investigations was to evaluate the sensitivity and specificity of anti-MS and -MPT51 antibodies as biomarkers for TB in HIV(-)TB(+) and HIV(+)TB(+) patients from a TB-endemic setting. Earlier studies also demonstrated the presence of these biomarkers during incipient subclinical TB. If these biomarkers correlate with incipient TB, their prevalence should be higher in asymptomatic HIV(+) subjects who are at a high-risk for TB. The second goal was to compare the prevalence of these biomarkers in asymptomatic, CD4(+) T cell-matched HIV(+)TB(-) subjects from India who are at high-risk for TB with similar subjects from US who are at low-risk for TB.

Methods And Results: Anti-MS and -MPT51 antibodies were assessed in sera from 480 subjects including PPD(+) or PPD(-) healthy subjects, healthy community members, and HIV(-)TB(+) and HIV(+)TB(+) patients from India. Results demonstrate high sensitivity (approximately 80%) of detection of smear-positive HIV(-)TB(+) and HIV(+)TB(+) patients, and high specificity (>97%) with PPD(+) subjects and endemic controls. While approximately 45% of the asymptomatic HIV(+)TB(-) patients at high-risk for TB tested biomarker-positive, >97% of the HIV(+)TB(-) subjects at low risk for TB tested negative. Although the current studies are hampered by lack of knowledge of the outcome, these results provide strong support for the potential of these biomarkers to detect incipient, subclinical TB in HIV(+) subjects.

Conclusions: These biomarkers provide high sensitivity and specificity for TB diagnosis in a TB endemic setting. Their performance is not compromised by concurrent HIV infection, site of TB and absence of pulmonary manifestations in HIV(+)TB(+) patients. Results also demonstrate the potential of these biomarkers for identifying incipient subclinical TB in HIV(+)TB(-) subjects at high-risk for TB.

Citing Articles

Accuracy of anti-mycobacterial protein 51 antibodies as a biomarker for latent TB infection in asymptomatic HIV positive individuals: a cross-sectional diagnostic study.

Namugga J, Musubika C, Niwagaba S, Mayito J, Sande O BMC Res Notes. 2025; 18(1):73.

PMID: 39962598 PMC: 11834177. DOI: 10.1186/s13104-025-07134-1.

Exploring the Potential of Exosomes as Biomarkers in Tuberculosis and Other Diseases.

Arya R, Jit B, Kumar V, Kim J Int J Mol Sci. 2024; 25(5).

PMID: 38474139 PMC: 10931916. DOI: 10.3390/ijms25052885.

Composition and Clinical Significance of Exosomes in Tuberculosis: A Systematic Literature Review.

Biadglegne F, Konig B, Rodloff A, Dorhoi A, Sack U J Clin Med. 2021; 10(1).

PMID: 33406750 PMC: 7795701. DOI: 10.3390/jcm10010145.

Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection.

Drain P, Bajema K, Dowdy D, Dheda K, Naidoo K, Schumacher S Clin Microbiol Rev. 2018; 31(4).

PMID: 30021818 PMC: 6148193. DOI: 10.1128/CMR.00021-18.

Elevated serum β2-microglobulin in individuals coinfected with hepatitis B and hepatitis D virus in a rural settings in Southwest Nigeria.

Okoror L, Ajayi A, Ijalana O BMC Res Notes. 2017; 10(1):719.

PMID: 29221492 PMC: 5721584. DOI: 10.1186/s13104-017-3015-9.

References

Hendrickson R, DOUGLASS J, Reynolds L, McNEILL P, Carter D, Reed S . Mass spectrometric identification of mtb81, a novel serological marker for tuberculosis. J Clin Microbiol. 2000; 38(6):2354-61. PMC: 86802. DOI: 10.1128/JCM.38.6.2354-2361.2000. View

Lane H, Masur H, Edgar L, Whalen G, Rook A, Fauci A . Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983; 309(8):453-8. DOI: 10.1056/NEJM198308253090803. View

Pai M, Gokhale K, Joshi R, Dogra S, Kalantri S, Mendiratta D . Mycobacterium tuberculosis infection in health care workers in rural India: comparison of a whole-blood interferon gamma assay with tuberculin skin testing. JAMA. 2005; 293(22):2746-55. DOI: 10.1001/jama.293.22.2746. View

Singh K, Dong Y, Belisle J, Harder J, Arora V, Laal S . Antigens of Mycobacterium tuberculosis recognized by antibodies during incipient, subclinical tuberculosis. Clin Diagn Lab Immunol. 2005; 12(2):354-8. PMC: 549317. DOI: 10.1128/CDLI.12.2.354-358.2005. View

Wood R, Middelkoop K, Myer L, Grant A, Whitelaw A, Lawn S . Undiagnosed tuberculosis in a community with high HIV prevalence: implications for tuberculosis control. Am J Respir Crit Care Med. 2006; 175(1):87-93. PMC: 1899262. DOI: 10.1164/rccm.200606-759OC. View

Samanich K, Belisle J, Laal S . Homogeneity of antibody responses in tuberculosis patients. Infect Immun. 2001; 69(7):4600-9. PMC: 98537. DOI: 10.1128/IAI.69.7.4600-4609.2001. View

Laal S, Samanich K, Sonnenberg M, Belisle J, OLeary J, Simberkoff M . Surrogate marker of preclinical tuberculosis in human immunodeficiency virus infection: antibodies to an 88-kDa secreted antigen of Mycobacterium tuberculosis. J Infect Dis. 1997; 176(1):133-43. DOI: 10.1086/514015. View

Houghton R, Lodes M, Dillon D, Reynolds L, Day C, McNeill P . Use of multiepitope polyproteins in serodiagnosis of active tuberculosis. Clin Diagn Lab Immunol. 2002; 9(4):883-91. PMC: 120014. DOI: 10.1128/cdli.9.4.883-891.2002. View

Singh K, Dong Y, Patibandla S, McMurray D, Arora V, Laal S . Immunogenicity of the Mycobacterium tuberculosis PPE55 (Rv3347c) protein during incipient and clinical tuberculosis. Infect Immun. 2005; 73(8):5004-14. PMC: 1201194. DOI: 10.1128/IAI.73.8.5004-5014.2005. View

10.

Moore D, Evans C, Gilman R, Caviedes L, Coronel J, Vivar A . Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med. 2006; 355(15):1539-50. PMC: 1780278. DOI: 10.1056/NEJMoa055524. View

11.

Steingart K, Henry M, Laal S, Hopewell P, Ramsay A, Menzies D . Commercial serological antibody detection tests for the diagnosis of pulmonary tuberculosis: a systematic review. PLoS Med. 2007; 4(6):e202. PMC: 1891320. DOI: 10.1371/journal.pmed.0040202. View

12.

Laal S, Samanich K, Sonnenberg M, Zolla-Pazner S, Phadtare J, Belisle J . Human humoral responses to antigens of Mycobacterium tuberculosis: immunodominance of high-molecular-mass antigens. Clin Diagn Lab Immunol. 1997; 4(1):49-56. PMC: 170474. DOI: 10.1128/cdli.4.1.49-56.1997. View

13.

Ansari N, Kombe A, Kenyon T, Hone N, Tappero J, Nyirenda S . Pathology and causes of death in a group of 128 predominantly HIV-positive patients in Botswana, 1997-1998. Int J Tuberc Lung Dis. 2002; 6(1):55-63. View

14.

Barrera L, de Kantor I, Ritacco V, Reniero A, Lopez B, Benetucci J . Humoral response to Mycobacterium tuberculosis in patients with human immunodeficiency virus infection. Tuber Lung Dis. 1992; 73(4):187-91. DOI: 10.1016/0962-8479(92)90084-w. View

15.

Weldingh K, Rosenkrands I, Okkels L, Doherty T, Andersen P . Assessing the serodiagnostic potential of 35 Mycobacterium tuberculosis proteins and identification of four novel serological antigens. J Clin Microbiol. 2005; 43(1):57-65. PMC: 540170. DOI: 10.1128/JCM.43.1.57-65.2005. View

16.

Huebner R, Schein M, Hall C, Barnes S . Delayed-type hypersensitivity anergy in human immunodeficiency virus-infected persons screened for infection with Mycobacterium tuberculosis. Clin Infect Dis. 1994; 19(1):26-32. DOI: 10.1093/clinids/19.1.26. View

17.

Abebe F, Holm-Hansen C, Wiker H, Bjune G . Progress in serodiagnosis of Mycobacterium tuberculosis infection. Scand J Immunol. 2007; 66(2-3):176-91. DOI: 10.1111/j.1365-3083.2007.01978.x. View

18.

Corbett E, Charalambous S, Moloi V, Fielding K, Grant A, Dye C . Human immunodeficiency virus and the prevalence of undiagnosed tuberculosis in African gold miners. Am J Respir Crit Care Med. 2004; 170(6):673-9. DOI: 10.1164/rccm.200405-590OC. View

19.

Getahun H, Harrington M, OBrien R, Nunn P . Diagnosis of smear-negative pulmonary tuberculosis in people with HIV infection or AIDS in resource-constrained settings: informing urgent policy changes. Lancet. 2007; 369(9578):2042-2049. DOI: 10.1016/S0140-6736(07)60284-0. View

20.

Foulds J, OBrien R . New tools for the diagnosis of tuberculosis: the perspective of developing countries. Int J Tuberc Lung Dis. 1998; 2(10):778-83. View