Risk Assessment of Tuberculosis in Immunocompromised Patients. A TBNET Study

Abstract

Author Contributions: M.S. made a substantial contribution to the conception and design of the work and to the acquisition, analysis, and interpretation of data for the work; wrote the manuscript; critically revised the manuscript for important intellectual content; and gave final approval of the current version to be published. F.v.L. made a substantial contribution to the conception and design of the work and to the interpretation of data for the work, performed statistical analysis, wrote the manuscript, critically revised the manuscript for important intellectual content, and gave final approval of the current version to be published. P.R. made a substantial contribution to the conception and design of the work and to the interpretation of data for the work, critically revised the manuscript for important intellectual content, and gave final approval of the current version to be published. C.L. made a substantial contribution to the conception and design of the work and to the acquisition, analysis, and interpretation of data for the work; wrote the manuscript; critically revised the manuscript for important intellectual content; and gave final approval of the current version to be published. All other authors made a contribution to the acquisition of the data for the work, critically revised the manuscript for important intellectual content, and gave final approval of the current version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Superior Sensitivity of Ex Vivo IFN-γ Release Assays as Compared to Skin Testing in Immunocompromised Patients

“…Our study provides a direct proof for the clinical notion that IGRAs are of higher sensitivity to detect a specific immune response as compared to the TST, particularly in immunocompromised patients (4,8,(13)(14)(15)(16). Unlike the TST, IGRAs were more closely associated with clinically assessable variables consistent with prior contact with mycobacterial antigens such as history of active tuberculosis, prior exposure to M. tuberculosis, long-term residence in a M. tuberculosis-endemic country or BCG vaccination.…”

“…evident by the fact that among discrepant results, TSTnegative/IGRA-positive constellations clearly predominated over TST-positive/IGRA-negative results. In contrast, in studies comparing commercial RD-1-based IGRA assays with TST responses, a positive TST in the presence of a negative IGRA is also frequently observed, which is usually scored as evidence for immunity toward BCG vaccination or NTM, especially in individuals with prior BCG vaccination (8,14). However, this discrepancy may to some extent also result from the fact that PPD comprises a mixture of different mycobacterial proteins as compared to single proteins such as ESAT-6 or CFP-10, a circumstance in which a TST would be more likely to become positive than an IGRA.…”

“…All transplant recipients were on a standard immunosuppressive drug regimen. To quantify the dosage of immunosuppressive drugs in transplant recipients, a drug score was calculated that included both the number of drugs as well as their dosage as previously described (8). The study was approved by the local ethics committee ( € Arztekammer des Saarlandes) and all individuals gave informed consent.…”

“…IGRAs are differentially affected by the level of immunosuppression Finally, test results for the three IGRAs were associated with the level of immunodeficiency in transplant recipients (Table 6), which included time after transplantation, the number of drugs and a drug score as an estimation for the overall level of immunosuppression, including number of drugs and their dosage as defined before (8). Of note, neither the time after transplantation as continuous variable nor as categorical variable (more or less than 1 year after transplantation) had an effect on the test results.…”

“…In a large multicenter trial focused on the comparative analysis of the two commercial IGRAs (i.e. ELISA and ELISPOT) with the TST in five different groups of immunocompromised patients, IGRAs appeared to be superior in detecting a latent infection with M. tuberculosis in patient groups with T cell-associated immunodeficiencies (8). These results may be indicative of a higher sensitivity of IGRAs in immunocompromised individuals, although a direct comparison between the IGRAs and the TST is formally hampered by the use of different antigens (region of difference [RD]-1 antigens ESAT-6 and CFP-10 in IGRAs vs. tuberculin PPD in the TST), which is generally neglected when interpreting discrepant test result.…”