Improved efficiency in detecting cellular immunity towards M. tuberculosis in patients receiving immunosuppressive drug therapy.
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.
Sester
Urban
U
Department of Internal Medicine IV, Nephrology, University of the Saarland, D-66421 Homburg, Germany.
Junker
Heike
H
Hodapp
Tobias
T
Schütz
Alexandra
A
Thiele
Bernhard
B
Meyerhans
Andreas
A
Köhler
Hans
H
Sester
Martina
M
D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000382:microbiology / Q000517:prevention & control; D006801:Humans; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D016030:Kidney Transplantation; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012882:Skin Tests; D014373:Tuberculin / Q000276:immunology; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology*
D007166:Immunosuppressive Agents; D014373:Tuberculin