IgG subclasses' response to a set of mycobacterial antigens in different stages of Mycobacterium tuberculosis infection

Abstract

Despite the reported high heterogeneity of the human immune response to tuberculosis (TB), new studies may contribute to the understanding of Mycobacterium tuberculosis immunopathogenesis. To investigate the patterns of humoral response during latent (LTBI) and active TB, we evaluated specific IgG subclasses' response, by ELISA, to a set of mycobacterial antigens (Rv2029c, Rv2031c, Rv2034, Rv2628, Rv3353c ESAT6:CFP10, and the new chimeric PstS1_(285-374):CFP10) in plasma samples from exposed uninfected controls (ExC, n = 24), LTBI (n = 61), and TB (n = 15) donors. In general, the TB group showed statistically higher levels of IgG1, and lower levels of IgG3. Keeping specificities ≥90%, the highest sensitivity for TB detection was observed for IgG1-ESAT6:CFP10 (93.3%), followed by IgG2-Rv3353 (86.7%), IgG1-Rv3353 (69.2%) and IgG1-PstS1_(285-374):CFP10 (53.3%). The combinatory of high IgG1-ESAT6:CFP10, followed by low IgG2-Rv3353c titers increased the specificity for TB detection to 100%. Only IgG3-ESAT6:CFP10 showed statistical differences between ExC and LTBI, detecting 50% of the LTBI donors. For the first time, higher levels of IgG2-PstS1_(285-374):CFP10 and IgG2-Rv3353 were observed in LTBI and ExC, as compared with a lower or absent immunoreactivity among TB. This study demonstrates differential modulation of subclasses' profiles for the stages of infection, which may contribute to the further development of new diagnostic tools.

Keywords: Humoral immunity; IgG; M. tuberculosis; Subclasses; Tuberculosis.