title: Maintenance of Mycobacterium tuberculosis-specific T cell responses in End Stage Renal Disease (ESRD) and implications for diagnostic efficacy.
abstract: End-stage renal disease (ESRD) patients exhibit elevated risk of tuberculosis (TB) reactivation, but current diagnostics, including the interferon gamma release assay (IGRA), exhibit poor sensitivity in ESRD. We tested 80 ESRD patients and found an 18.75% prevalence of IGRA positivity. A subset of patients was assessed for Mtb-specific expression of 44 cytokines/chemokines, and CD4+ T cell phenotype and function. Similar to non-ESRD IGRA+ individuals, Mtb-specific IFNγ, IL-1RA, IP-10, MCP-3 and IL-2 responses were identified in the ESRD IGRA+ group. 27% of the ESRD IGRA- group exhibited MCP-3 or IL-2 Mtb-specific responses, which may identify cases of latent TB infection in ESRD. Stimulation of PBMC with PPD demonstrated similar CD4+ T cell production of IFNγ, TNFα and GM-CSF by ESRD patients. The reported low sensitivity of the IGRA in ESRD cohorts is therefore unlikely to be due to poor T cell cytokine secretion, and may instead reflect defects in antigen presentation.
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada; TB-HIV Co-infection Unit, National HIV and Retrovirology Laboratory, JC Wilt Infectious Disease Research Centre, Winnipeg, MB, Canada. Electronic address: umjuno@myumanitoba.ca.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Juno
authors.affiliation: TB-HIV Co-infection Unit, National HIV and Retrovirology Laboratory, JC Wilt Infectious Disease Research Centre, Winnipeg, MB, Canada.
authors.forename: Jillian L M
authors.initials: JLM
authors.lastname: Waruk
authors.affiliation: TB-HIV Co-infection Unit, National HIV and Retrovirology Laboratory, JC Wilt Infectious Disease Research Centre, Winnipeg, MB, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Mesa
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Carmen
authors.initials: C
authors.lastname: Lopez
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada; Health Sciences Centre Renal Program, Winnipeg, MB, Canada.
authors.forename: Joe
authors.initials: J
authors.lastname: Bueti
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada; TB-HIV Co-infection Unit, National HIV and Retrovirology Laboratory, JC Wilt Infectious Disease Research Centre, Winnipeg, MB, Canada.
authors.forename: T Blake
authors.initials: TB
authors.lastname: Ball
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada; TB-HIV Co-infection Unit, National HIV and Retrovirology Laboratory, JC Wilt Infectious Disease Research Centre, Winnipeg, MB, Canada.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Kiazyk
mesh_terms: D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D054410:Chemokine CCL7 / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000378:metabolism; D055985:Latent Tuberculosis / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000502:physiology; D012372:ROC Curve
chemical_list: D054410:Chemokine CCL7; D016207:Cytokines; D007371:Interferon-gamma
keywords: Diabetes; ESRD; IGRA; MCP-3; TB