IgA and IgG against Mycobacterium tuberculosis Rv2031 discriminate between pulmonary tuberculosis patients, Mycobacterium tuberculosis-infected and non-infected individuals

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.

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

“…In recent years, there has been more focus on investigating the role of antibodies and innate cells in TB infection and disease (24,25). This interest in humoral immunity in Mtb is evidenced by a mounting number of studies that have identified specific antibody targets, and structural or functional differences that are observed during different TB disease states (26)(27)(28)(29)(30). For example, while Mtb-specific IgG titers alone have been insufficient in distinguishing between latent and active TB, refinement of these correlates using additional isotypes, subclasses, and other Fc modifications are underway (see Figure 1) (31)(32)(33)(34)(35).…”

PPE 59 immunoreactivity in tuberculosis patients: IgA immunodominance to that IgG and IgM

“…Comparing with other serological biomarkers associated with risk factor for TB. Studies with different antigens showed that IgG ESAT6/16 kDa/HBHA was increased in active TB (declining after treatment), and in latently infected contact, suggesting that speci c antibodies were associated with the bacillary load [30].…”

Immunoglobulin profile and B-cell frequencies are altered with changes in the cellular micro-environment independent of the stimulation conditions

“…Research has implicated IgA and IgG as leaders in protective anti-TB humoral immunity (Balu et al , 2011; Achkar, Chan and Casadevall, 2015; Abebe et al , 2018). The exact mechanisms by which these immunoglobulins achieve the protective effect is still unknown, and further investigation into their cellular targets is needed to better understand the role they play during TB disease (Li et al , 2017).…”