Journal Article

Improved efficiency in detecting cellular immunity towards <i>M. tuberculosis</i> in patients receiving immunosuppressive drug therapy

Urban Sester, Heike Junker, Tobias Hodapp, Alexandra Schütz, Bernhard Thiele, Andreas Meyerhans, Hans Köhler and Martina Sester

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 21, issue 11, pages 3258-3268
Published in print November 2006 | ISSN: 0931-0509
Published online August 2006 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfl416
Improved efficiency in detecting cellular immunity towards M. tuberculosis in patients receiving immunosuppressive drug therapy

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Background. Reactivation of a latent Mycobacterium tuberculosis infection in immunocompromised individuals is associated with significant morbidity and mortality. The limited sensitivity of the established tuberculin skin-test in identifying latently infected patients on immunosuppressive drug therapy represents a major obstacle to better tuberculosis control after transplantation.

Methods. In this study, a quantitative flow-cytometric whole-blood assay and the skin-test were comparatively evaluated towards both diagnostic power and practicability in 117 long-term renal transplant recipients (age 53.1 ± 14.8 years; 7.0 ± 5.0 years after transplantation) in a low-prevalence region.

Results. Among the aforementioned renal transplant recipients, a high proportion (52.14%) had purified protein-derivative (PPD)-specific T-cell-immunity in vitro. Despite immunosuppression, prevalence as well as median frequencies of PPD-specific T-cells (0.22%; >0.05–4.71%) were as high as previously reported for immunocompetent individuals and haemodialysis patients. In contrast to in vitro testing, skin testing was less practicable in an ambulatory setting. Moreover, skin-test reactivity was significantly reduced as only 50.0% of patients with PPD-reactivity in vitro were skin-test positive. T-cell reactivity towards early secretory antigenic target-6 (ESAT-6), a protein specific for M. tuberculosis but absent from the bacillus Calmette–Guerin BCG-vaccine strain, was found in 52.9% of all individuals with PPD-reactivity in vitro.

Conclusions. In conclusion, the whole-blood assay reveals a high prevalence of latent tuberculosis infection in renal transplant recipients. It may represent a valuable alternative to skin testing as the test result is not adversely affected by immunosuppression. Moreover, reactivity towards ESAT-6 allows the distinction of a latent infection from BCG-induced reactivity. The assay is well-suited for use in screening programmes and may facilitate the management of tuberculosis infection in immunocompromised individuals.

Keywords: bacterial infection; human; immunosuppression; Mycobacterium tuberculosis; T-cells; transplantation

Journal Article.  5500 words.  Illustrated.

Subjects: Nephrology

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