Serological Markers of Pulmonary Tuberculosis and of Response to Anti-Tuberculosis Treatment in a Patient Population in Guinea

Abstract

The aim of the study was to evaluate serological correlates of active tuberculosis and of response to antituberculosis treatment in a cohort of HIV-negative patients with pulmonary tuberculosis studied at diagnosis and during treatment at the Service de Pneumo-Phtisiologie, Centre Hospitalier-Universitaire Ignace Deen, Conakry, Republic of Guinea. Two similar cohorts of HIV-negative healthy households of patients and healthy community controls were included in the study. Plasma samples were obtained from 168 untreated tuberculosis patients, 167 healthy household controls, and 168 healthy community controls. Serial plasma samples were also obtained from the tuberculosis patients at 2 and 8 months after initiation of chemotherapy. IgG antibody levelswere measured by an enzyme-linked immunosorbent assay (ELISA) using ten purified M. tuberculosis antigens. ELISA results were analysed by comparing geometric means of data. Of the ten antigens tested, five (14kDa Ag, 19kDa Ag, AlaDH, MS, and MPT83) elicited similar antibody responses in untreated TB patients and controls. In contrast, levels of three antibodies (ESAT-6, LAM, and 38kDa Ag) were higher in untreated TB patients than in household or community controls (p < 0.0001). Levels were higher in untreated patients than in community controls also for the anti-Rv2626c antibody (p = 0.0001) and, at a lower significance level, for the anti-FdxA antibody (p < 0.025). Antibody levels against ESAT-6 and Rv2626c decreased during therapy, while antibody levels to the 38 kDa antigen and LAM increased during therapy; FdxA antibody levels did not vary with treatment. Neither severity of presentation nor chest X-ray patterns affected levels of these antibodies before treatment. In contrast, after the 8-month therapeutic course, patients who presented with moderate/severe disease had higher levels of anti-ESAT-6, anti-FdxA, and anti-38kDa antibodies than those of patients with mild disease onset. Patients with bilateral lung lesions had significantly higher anti-38kDa and anti-LAM levels, both at diagnosis and after 8-month treatment, than patients with lesions involving only one lung. Antibodies to alanine dehydrogenase and malate synthetase measured at initiation of treatment were higher in tuberculosis patients who subsequently failed therapy than in those who were cured. The main conclusions ofthe study are: a) plasma levels of antibodies to a number of M. tuberculosis represent serological correlates of active disease; b) these correlates are affected in an antigen-specific fashion by anti-tuberculosis treatment; c) particular serological markers may be predictive of treatment outcome.

Assessment of Three Commercially Available Serologic Assays for Detection of Antibodies to Mycobacterium tuberculosis and Identification of Active Tuberculosis

“…These shortcomings result in the unnecessary treatment of many individuals who may not need it (3,17,32,45). While the tuberculin skin test (TST) and the QuantiFERON-TB Gold (QFT-G), the traditional methods for latent TB infection screening, rely on the cell-mediated response, the humoral response appears to correlate with the progression of the infection to active TB disease (5,6,11,15,20,21).…”

“…These shortcomings result in the unnecessary treatment of many individuals who may not need it (3,17,32,45). While the tuberculin skin test (TST) and the QuantiFERON-TB Gold (QFT-G), the traditional methods for latent TB infection screening, rely on the cell-mediated response, the humoral response appears to correlate with the progression of the infection to active TB disease (5,6,11,15,20,21).Many studies have been conducted to evaluate the utility of individual specific Mycobacterium tuberculosis antigens for detecting antibodies in patients with active TB disease (1,7,10,11,20,21,25,26,29,38,39,45,46). Several of these antigens have been developed into commercial assays capable of detecting M. tuberculosis antibodies (4,28,35,53).…”

Evaluation of Antigen-Specific Immunoglobulin G Responses in Pulmonary Tuberculosis Patients and Contacts

“…Notably, while serodiagnosis of TB by combining immunoglobulin classes was suggested as a useful point-of-care test in South Africa (12), poor performance of the commercial serological tests for diagnosing pulmonary TB was reported in India (13), and to date, no commercial serodiagnostic tests have demonstrated acceptable sensitivity and specificity for routine laboratory use. In previously developed tests, these have varied, depending on the recombinant antigens tested (14), and changes in antibody levels following suc-cessful anti-TB treatment also varied with different antigens (15)(16)(17). Inconsistent M. tuberculosis antigen-specific antibody titers were also found in populations with various levels of M. tuberculosis exposure (18).…”

Comparison of serological responses in two different populations with pulmonary tuberculosis

“…The results permit us to suggest that these isotypes are markers of active infection and could be predictive of treatment outcome in this population, such as has been reported by others authors, who have suggested that the levels of antibodies to M. tuberculosis represent serological correlates of active disease since these were affected in an antigen-specific fashion by anti-TB treatment (Azzurri et al 2006).…”