NDT Advance Access originally published online on August 25, 2006
Nephrology Dialysis Transplantation 2006 21(11):3258-3268; doi:10.1093/ndt/gfl416
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Improved efficiency in detecting cellular immunity towards M. tuberculosis in patients receiving immunosuppressive drug therapy
1Department of Internal Medicine IV, 2Department of Virology, University of the Saarland, D-66421 Homburg and 3Institute for Immunogenetics, 67655 Kaiserslautern, Germany
Correspondence and offprint requests to: Prof. Dr H. Köhler, MD, Department of Internal Medicine IV, Nephrology, University of the Saarland, D-66421 Homburg, Germany. Email: inhkoe{at}uniklinikum-saarland.de
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%; >0.054.71%) 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 CalmetteGuerin 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
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