Serological and cellular inflammatory signatures in end-stage kidney disease and latent tuberculosis

Milla R McLean; Kathleen M Wragg; Ester Lopez; Sandra A Kiazyk; Terry Blake Ball; Joe Bueti; Stephen J Kent; Jennifer A Juno; Amy W Chung

doi:10.1002/cti2.1355

Serological and cellular inflammatory signatures in end-stage kidney disease and latent tuberculosis

Clin Transl Immunology. 2021 Nov 5;10(11):e1355. doi: 10.1002/cti2.1355. eCollection 2021.

Authors

Milla R McLean¹, Kathleen M Wragg¹, Ester Lopez¹, Sandra A Kiazyk^{2

3}, Terry Blake Ball², Joe Bueti^{4

5

6}, Stephen J Kent^{1

7

8}, Jennifer A Juno¹, Amy W Chung¹

Affiliations

¹ Department of Microbiology and Immunology University of Melbourne at The Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia.
² National HIV and Retrovirology Laboratory National Microbiology Laboratory JC Wilt Infectious Diseases Research Centre Public Health Agency of Canada Winnipeg MB Canada.
³ Department of Medical Microbiology and Infectious Diseases University of Manitoba Winnipeg MB Canada.
⁴ Department of Internal Medicine University of Manitoba Winnipeg MB Canada.
⁵ Section of Nephrology Department of Internal Medicine University of Manitoba MB Canada.
⁶ Health Sciences Centre Winnipeg MB Canada.
⁷ Australian Research Council Centre for Excellence in Convergent Bio-Nano Science and Technology University of Melbourne Melbourne VIC Australia.
⁸ Melbourne Sexual Health Centre and Department of Infectious Diseases Alfred Hospital and Central Clinical School Monash University Melbourne VIC Australia.

Abstract

Objectives: Tuberculosis comorbidity with chronic diseases including diabetes, HIV and chronic kidney disease is of rising concern. In particular, latent tuberculosis infection (LTBI) comorbidity with end-stage kidney disease (ESKD) is associated with up to 52.5-fold increased risk of TB reactivation to active tuberculosis infection (ATBI). The immunological mechanisms driving this significant rise in TB reactivation are poorly understood. To contribute to this understanding, we performed a comprehensive assessment of soluble and cellular immune features amongst a unique cohort of patients comorbid with ESKD and LTBI.

Methods: We assessed the plasma and cellular immune profiles from patients with and without ESKD and/or LTBI (N = 40). We characterised antibody glycosylation, serum complement and cytokine levels. We also assessed classical and non-classical monocytes and T cells with flow cytometry. Using a systems-based approach, we identified key immunological features that discriminate between the different disease states.

Results: Individuals with ESKD exhibited a highly inflammatory plasma profile and an activated cellular state compared with those without ESKD, including higher levels of inflammatory antibody Fc glycosylation structures and activated CX3CR1⁺ monocytes that correlate with increased inflammatory plasma cytokines. Similar elevated inflammatory signatures were also observed in ESKD⁺/LTBI⁺ compared with ESKD^-/LTBI⁺, suggesting that ESKD induces an overwhelming inflammatory immune state. In contrast, no significant inflammatory differences were observed when comparing LTBI⁺ and LTBI^- individuals.

Conclusion: Our study highlights the highly inflammatory state induced by ESKD. We hypothesise that this inflammatory state could contribute to the increased risk of TB reactivation in ESKD patients.

Keywords: end‐stage kidney disease; glycosylation; inflammation; monocytes; tuberculosis; unconventional T cells.