Elisa Petruccioli1, Linda Petrone1, Valentina Vanini1, Gilda Cuzzi1, Assunta Navarra2, Gina Gualano3, Fabrizio Palmieri3, Enrico Girardi2, Delia Goletti4. 1. Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI) IRCCS, Via Portuense 292, Rome 00149, Italy. 2. Department of Epidemiology and Preclinical Research, INMI, Rome, Italy. 3. Clinical Department, INMI, Rome, Italy. 4. Translational Research Unit, Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI) IRCCS, Via Portuense 292, Rome 00149, Italy. Electronic address: delia.goletti@inmi.it.
Abstract
UNLABELLED: There are still no reliable tests to distinguish active tuberculosis (TB) from latent TB infection (LTBI). Assessment of CD27 modulation on CD4⁺ T-cells has been suggested as a tool to diagnose different TB stages. OBJECTIVES: To use several cytometric approaches to evaluate CD27 expression on Mycobacterium tuberculosis (Mtb)-specific CD4⁺ T-cells to differentiate TB stages. METHODS: 55 HIV-uninfected subjects were enrolled: 13 active TB; 12 cured TB; 30 LTBI. Whole blood was stimulated with RD1-proteins or Cytomegalovirus-lysate (CMV). Interferon (IFN)-γ response was evaluated by cytometry. The proportion of CD27(±) within the IFN-γ⁺ CD4⁺ T-cells or RATIO of the CD27-median fluorescence intensity (MFI) of CD4⁺ T-cells over the CD27 MFI of IFN-γ⁺ CD4⁺ T-cells was evaluated. RESULTS: The greatest diagnostic accuracy in discriminating active TB vs. LTBI or cured TB was reached by evaluating the CD27(+) CD45RA(-) cells within the IFN-γ⁺ CD4⁺ T-cell subset (76.92 sensitivity for both, and 90% and 91.67% specificity, respectively), although the use of the CD27 MFI RATIO allows for stricter data analysis, independent of the operator. CONCLUSIONS: the study of CD27 expression using different approaches, whether it involves evaluation of CD45RA expression or not, is a robust biomarker for discriminating TB stages.
UNLABELLED: There are still no reliable tests to distinguish active tuberculosis (TB) from latent TB infection (LTBI). Assessment of CD27 modulation on CD4⁺ T-cells has been suggested as a tool to diagnose different TB stages. OBJECTIVES: To use several cytometric approaches to evaluate CD27 expression on Mycobacterium tuberculosis (Mtb)-specific CD4⁺ T-cells to differentiate TB stages. METHODS: 55 HIV-uninfected subjects were enrolled: 13 active TB; 12 cured TB; 30 LTBI. Whole blood was stimulated with RD1-proteins or Cytomegalovirus-lysate (CMV). Interferon (IFN)-γ response was evaluated by cytometry. The proportion of CD27(±) within the IFN-γ⁺ CD4⁺ T-cells or RATIO of the CD27-median fluorescence intensity (MFI) of CD4⁺ T-cells over the CD27 MFI of IFN-γ⁺ CD4⁺ T-cells was evaluated. RESULTS: The greatest diagnostic accuracy in discriminating active TB vs. LTBI or cured TB was reached by evaluating the CD27(+) CD45RA(-) cells within the IFN-γ⁺ CD4⁺ T-cell subset (76.92 sensitivity for both, and 90% and 91.67% specificity, respectively), although the use of the CD27 MFI RATIO allows for stricter data analysis, independent of the operator. CONCLUSIONS: the study of CD27 expression using different approaches, whether it involves evaluation of CD45RA expression or not, is a robust biomarker for discriminating TB stages.
Authors: Elisa Petruccioli; Thomas J Scriba; Linda Petrone; Mark Hatherill; Daniela M Cirillo; Simone A Joosten; Tom H Ottenhoff; Claudia M Denkinger; Delia Goletti Journal: Eur Respir J Date: 2016-11-11 Impact factor: 16.671
Authors: L Petrone; V Vanini; M Amicosante; A Corpolongo; M A Gomez Morales; A Ludovisi; G Ippolito; E Pozio; A Teggi; D Goletti Journal: Parasite Immunol Date: 2017-12 Impact factor: 2.280
Authors: Andrew R DiNardo; Anna M Mandalakas; Gugu Maphalala; Godwin Mtetwa; Temhlanga Mndzebele; Piluca Ustero; Makhosazana Hlatshwayo; Emily M Mace; Jordan S Orange; George Makedonas Journal: Mediators Inflamm Date: 2016-03-02 Impact factor: 4.711