Science Bite - 3 min Oral Presentation (Students and ECRs only) Lorne Infection and Immunity 2020

Inflammatory serum markers and antibodies  in patients with end-stage renal disease co-infected with latent tuberculosis (#70)

Milla R McLean 1 , Jennifer Juno 1 , Sandra Kiazyk 2 3 , Terry B Ball 2 3 , Stephen J Kent 1 4 5 , Amy W Chung 1
  1. Peter Doherty Institute for Infection and Immunity, Melbourne University, Melbourne, VIC, Australia
  2. National Laboratory for HIV Immunology, National HIV & Retrovirology Laboratories Public Health Agency of Canada, Manitoba, Canada
  3. Department of Immunology, University of Manitoba, Manitoba, Canada
  4. Melbourne Sexual Health Centre, Infectious Diseases Department, Alfred Health, Central Clinical School, Monash University, Melbourne, Australia
  5. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, Australia

Patients with end-stage renal disease (ESRD) have a 52.5-fold increased risk of Mycobacterium Tuberculosis (TB) reactivation from latent to active disease (1). The immunological reason for ESRD associated TB reactivation is unclear. This study is of Canadian patients with ESRD (n=10), ESRD co-infected with Latent Tuberculosis (Ltb) (n=10), Ltb infection only (n=10) and negative controls (n=10). These groups are matched in diabetic status. Over 320 serological features using multiplex and glycosylation methods were assessed including inflammatory cytokines, antibody binding to 17 Mtb-specific antigens, complement, Fc-receptor binding, glycosylation patterns as well as correlating these serum markers with monocyte and T cell data that has been conducted on this cohort (2, 3, 4). Systems serological approach using machine learning algorithms determined differentiating features. All patients with ESRD exhibited substantial elevations in 20 cytokines most notable being those associated with pro-inflammation; Osteopontin (n=0.006), IL-35 (p=0.001), Osteocalcin (p=0.003), IL-2 (p<0.0001), APRIL (n=<0.0001) and TSLP (p<0.0001). Interestingly, patients with ESRD and LTB exhibited elevations in MMP-3 (p=0.014) cf. patients with ESRD. Anti-inflammatory IL-10 (p=0.001) and TWEAK (p=0.006) differentiated between Ltb and ESRD/Ltb patients. Further, the pro-inflammatory agalactosylated and fucosylated IgG was enhanced in patients with co-morbidity compared to Ltb. Complement proteins Factor D (adipsin), Factor I and C1q were significantly elevated in co-morbid individuals (p<0.0001, p=0.04, p=0.009). This data reveals cytokines, glycosylation patterns and IgG subclass binding differentiates ESRD/Ltb from Ltb. We identify an inflammatory environment of ESRD being one which encourages macrophage activation which is pertinent given TB infects these cells. The co-infected group exhibits these same highly inflammatory biomarkers, which we hypothesise impacts their ability to prevent reactivation. With the growing double burden of disease in developing countries, this research is highly relevant and novel in that it looks at the immune state in co-infection of non-communicable and communicable disease.

  1. (1) Hussein, M.M., J.M. Mooij, and H. Roujouleh, Tuberculosis and chronic renal disease. Semin Dial, 2003. 16(1): p. 38-44
  2. (2) Juno, J.A., Waruk, J.L.M., Harris, A., Mesa, C., Lopez, C., Bueti, J., Ball, T.B., and Kiazyk, S.A. (2017). gammadelta T-cell function is inhibited in end-stage renal disease and impacted by latent tuberculosis infection. Kidney Int 92, 1003-1014.
  3. (3) Juno, J.A., Waruk, J.L.M., Mesa, C., Lopez, C., Bueti, J., Ball, T.B., and Kiazyk, S.A. (2016). Maintenance of Mycobacterium tuberculosis-specific T cell responses in End Stage Renal Disease (ESRD) and implications for diagnostic efficacy. Clin Immunol 168, 55- 63.
  4. (4) Juno, J.A., Waruk, J.L.M., Wragg, K.M., Mesa, C., Lopez, C., Bueti, J., Kent, S.J., Ball, T.B., and Kiazyk, S.A. (2018). Mucosal-Associated Invariant T Cells Are Depleted and Exhibit Altered Chemokine Receptor Expression and Elevated Granulocyte Macrophage- Colony Stimulating Factor Production During End-Stage Renal Disease. Front Immunol 9, 1076.