title: Superior Sensitivity of Ex Vivo IFN-γ Release Assays as Compared to Skin Testing in Immunocompromised Patients.
abstract: Comparative assessment of the tuberculin skin testing (TST) and commercial IFN-γ release-assays (IGRAs) is hampered by the use of different antigens (tuberculin PPD in TST vs. ESAT-6/CFP-10 in IGRAs). Thus, PPD was used as a common stimulus to compare performance of the TST and three IGRAs in 72 controls, 101 hemodialysis patients and 100 renal transplant recipients. Results of the TST were compared with PPD-induced IFN-γ induction in vitro detected by ELISPOT, ELISA or a flow-cytometric FACS assay. Percentages of positive tests were significantly lower in TST (9.2%) compared to ELISA (55.3%), ELISPOT (45.3%) and FACS (44.9%, p < 0.0001). Agreement between TST and IGRAs was highest for controls (κ = 0.19-0.32) and poor in immunocompromised patients (κ = 0 for transplant patients, κ = 0.06-0.13 for hemodialysis patients). Discrepant results were largely TST negative and IGRA positive. Among IGRAs, agreement was highest between ELISPOT and FACS (κ = 0.61). Unlike TST, all IGRAs were associated with variables of mycobacterial exposure. Among IGRAs, the FACS assay was least affected by the level of immunosuppression. In conclusion, both the percentage of positive results and between-test-agreement were higher with IGRAs as compared to TST. This indicates superiority of IGRAs in detecting a PPD-specific immune response which may also apply for immunity toward Mycobacterium tuberculosis-specific antigens.
authors.affiliation: Department of Transplant and Infection Immunology, Saarland University, Homburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Scholman
authors.affiliation: Center for Chronic Immunodeficiency & Center for Infectious Diseases, Medical Center, University of Freiburg, Freiburg im Breisgau, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Straub
authors.affiliation: Clinical Epidemiology and Medical Statistics Unit, Department of Biomedical Sciences, University of Sassari-Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sotgiu
authors.affiliation: Department of Transplant and Infection Immunology, Saarland University, Homburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Elsäßer
authors.affiliation: Department of Internal Medicine IV, Saarland University, Homburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Leyking
authors.affiliation: Lionex Diagnostics & Therapeutics GmbH, Braunschweig, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Internal Medicine IV, Saarland University, Homburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Sester
authors.affiliation: Center for Chronic Immunodeficiency & Center for Infectious Diseases, Medical Center, University of Freiburg, Freiburg im Breisgau, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Wagner
authors.affiliation: Department of Transplant and Infection Immunology, Saarland University, Homburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sester
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016867:Immunocompromised Host; D059425:Interferon-gamma Release Tests; D016030:Kidney Transplantation; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012680:Sensitivity and Specificity; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology
keywords: Clinical decision-making; complication: infectious; immune deficiency; infection; mycobacterial; risk assessment/risk stratification