Abstract

CD4+ T cells are required for protection against tuberculosis (TB) disease progression, but interest in the role of antibodies in early protection, as biomarkers for disease status, and use in diagnostic tests has recently increased. In this study we analyzed plasma antibody levels in TB cases before and after treatment in both HIV-positive and -negative individuals and compared them with tuberculin skin test (TST+) (latently infected) household contacts (HHC). We also analyzed HHC that subsequently progressed to active disease within 2 years in order to see if antibodies play a role in protection against disease progression. We used a commercially available kit to 38 kDa antigen and lipoarabinomannan (LAM) and found that immunoglobulin (Ig) G levels were 4-fold higher in subjects with disease compared to latently infected controls (P<0.001) and were 2-fold higher than pretreatment levels following successful TB treatment (P<0.001 compared to both pretreated cases and latently infected controls). HIV infection resulted in low antibody levels regardless of disease status or treatment outcome. Furthermore, levels in disease progressors (incident cases) were similar to nonprogressors and were not elevated until just prior to disease progression confirming previous reports that IgG antibodies, at least in the periphery, do not confer protection against TB disease progression.

Highlights

  • Protective immunity to Mycobacterium tuberculosis (MTb) primarily requires CD4+ effector T cells as evidenced by a 6-fold increase in the likelihood of developing TB with decreasing CD4+ T cell counts in HIV-infected individuals [1]

  • Analysis of plasma IgG antibody levels to LAM/38 kDa was performed in confirmed TB cases (HIV negative (n = 76) or HIV-positive (n = 77) before and after (6 months) of treatment and compared with Test positive (TST)+ (>10 mm induration) HIV-negative household contacts

  • We found absolute levels of IgG to be significantly higher in HIV-negative TB cases compared to TST+ household contacts (HHC) (Figure 1(a)) but not for HIV-positive subjects who had similar levels to the TST+ HHC (Figure 1(a))

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Summary

Introduction

Protective immunity to Mycobacterium tuberculosis (MTb) primarily requires CD4+ effector T cells as evidenced by a 6-fold increase in the likelihood of developing TB with decreasing CD4+ T cell counts in HIV-infected individuals [1]. Determining the precise role of antibodies in TB is problematic since TB antibody profiles are highly heterogeneous and influenced by multiple parameters such as bacillary burden [2], the stage of bacterial cycle [3], and HIV coinfection [4]. Antibodies to LAM have been found in the urine of subjects with active TB disease, [8] and studies have shown an increase in antibody levels to different TB antigens following successful TB treatment [6, 9]. HIV infection does not appear to affect antibody levels to a number of different antigens [6, 8] with antibodies to LAM increasing in the urine of subjects with advanced immunosuppression [7] a recent paper has shown differential antibody levels depending on HIV status [10]. In this study we evaluated HIV-positive and HIVnegative TB cases before and after treatment and compared

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