Abstract
As part of a major project to investigate protective and diagnostic immune markers against tuberculosis (TB), we measured antibody isotype responses to Mycobacterium tuberculosis (Mtb) antigens (LAM, Rv2031, and HBHA) in cohorts of 149 pulmonary tuberculosis patients (PTBP), 148 household contacts (HHCs), and 68 community controls (CCs) in an endemic setting. ELISA was used to measure levels of IgA, IgG, and IgM from sera of cohorts at baseline, and at 6 and 12 months from entry. The results show that there were significant differences in IgA, IgG, and IgM responses to the different antigens and in the three cohorts. At baseline, the level of IgM against RV2031 and LAM did not vary between cohorts, but the levels of IgA and IgG against Rv2031 were significantly higher in PTB patients than HHCs and CCs, followed by HHCs, and the lowest in CCs. In patients, there was a significant variation in antibody responses before and after chemotherapy. The levels of IgA and IgG against HBHA, and IgA against Rv2031 decreased significantly and remained low, while IgA and IgG against LAM increased significantly and remained high following chemotherapy. However, the levels of IgM against Rv2031 and LAM increased at 6 months but decreased again at 12 months. IgM against HBHA did not show any significant variation before and after chemotherapy. Similarly, there were also significant variations in antibody responses in HHCs over time. Our results show that there are significant variations in IgA, IgG and IgM responses to the different antigens and in the three cohorts, implying that not all antibody isotype responses are markers of clinical TB. In addition, the current and previous studies consistently show that IgA and IgG against Rv2031 discriminate between clinical disease, Mtb-infected and non-infected individuals.
Highlights
Tuberculosis (TB) caused mainly by Mycobacterium tuberculosis (Mtb) remains one of the leading cause of death due to an infectious agent
The results show that the levels of IgA and IgG against Rv2031 were significantly higher in untreated PTB patients, followed by household contacts (HHCs) and the lowest in community controls (CCs)
In a study carried out in a pastoral community, our group reported that IgA against ESAT-6/CFP-10 and Rv2031 discriminated between pulmonary TB patients, healthy-Mtb-infected and non-infected individuals [27]
Summary
Tuberculosis (TB) caused mainly by Mtb remains one of the leading cause of death due to an infectious agent. Efforts to replace BCG with an efficacious vaccine or to augment very little, partly because of lack of knowledge about correlates of protective immunity [2,3,4,5]. Efforts made to develop an efficacious vaccine based on cell-mediated immunity (mainly interferon-gamma production by CD4+ T cells) did not yield the desired results. Lipo-arabinomannan (LAM), which is one of the major components of Mtb cell wall is associated with virulence and immuno-pathology, including inhibition of interferon-gamma-mediated macrophage activation [12], inhibition of T cell proliferation [13] or induction of T cell anergy [14, 15], inhibition of IL-12 production [16], inhibition of neutrophil recruitment [17], and inhibition of dendritic cell function and Mtb-induced apoptosis [18]. TB associated clinical manifestations, namely fever, weight loss, and tissue necrosis have been attributed to LAM-induced cytokine production [21]
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