Poster Presentation Lorne Infection and Immunity 2013

Dimeric immunoglobulin A: a novel biomarker for TB serodiagnostics (#140)

Khayriyyah Mohd Hanafiah 1 2 , Mary Garcia 1 , Katherine Lieschke 1 3 , Joy Liu 1 3 , Nadine Barnes 1 , Rosemary Ffrench 1 2 , David Anderson 1 2 3
  1. Macfarlane Burnet Institute, Melbourne, Victoria, Australia
  2. Department of Immunology, Monash University, Clayton, Victoria, Australia
  3. Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia

M. tuberculosis (MTB) primarily infects lung mucosa. Secreted antibodies, mainly dimeric IgA (dIgA), are important host responses in mucosal infection but neglected in diagnostic research1 2 . We hypothesize that residual MTB-specific dIgA are present in sera of persons with active TB, and have potential as markers of active tuberculosis (TB) along with IgA and IgG.

Active TB (n=60) and non-TB control (n=50) sera from Vietnam (FIND) were screened for MTB-specific IgA and IgG with MTB H37Rv antigens (BEI Resources) using indirect ELISA and commercial kits, Anda A60 and Omega Pathozyme Myco. Assays were repeated using recombinant polymeric immunoglobulin receptor (pIgR) to detect MTB-specific dIgA.

At cutoff of 3 standard deviations (3SD) from mean reactivity of non-TB controls, sensitivity/specificity of multiantigen-specific dIgA, IgA and IgG are 43%/80%, 43%/92%, and 43%/90%, respectively. At cutoff of 6SD, sensitivity/specificity of multiantigen-specific dIgA, IgA and IgG are 27%/98%, 15%/100% and 5%/98%, respectively. In active TB samples, specific-IgA reactivity correlates significantly with dIgA and IgG, but dIgA reactivity does not correlate with IgG. Many active TB samples are reactive on ≥5 antigen-isotype (24/60), some are uniquely reactive on one isotype only (dIgA: 8/60; IgA: 6/60; IgG: 7/60), or not reactive on any of the MTB-specific isotypes tested (5/60). Sensitivity/specificity of best combination of antigen-isotypes is 83%/88%.

DIgA is a useful novel biomarker of active TB detecting unique true positives independent of total IgG and IgA response. Heterogeneous antibody response to MTB implies a wide spectrum of seroimmunological states in active infection. The MTB immunoproteome response on dIgA and IgA appears different from IgG based on these results3 . Combination of specific-dIgA, IgA and IgG responses may be required for developing serodiagnostics with acceptable sensitivity and specificity.

  1. Kaetzel CS. The polymeric immunoglobulin receptor: bridging innate and adaptive immune responses at mucosal surfaces. Immunological Reviews, 2005; 206: 83–99.
  2. Woof JM and Russell MW. Mucosal Immunology, 2011; 4: 590-597.
  3. Kunnath-Velayudhan S, Salamon H, Wang HY, Davidow AL, Molina DM, Huynh VT, et al. Dynamic antibody responses to the Mycobacterium tuberculosis proteome. Proc Natl Acad Sci. 2010;107:14703-8.