IFN-γ and IgG responses to Mycobacterium tuberculosis latency antigen Rv2626c differentiate remote from recent tuberculosis infection

Abstract

tuberculin skin test (tSt) and ifn-γ release assays are currently used to detect Mycobacterium tuberculosis (Mtb) infection but none of them differentiate active from latent infection (LTBI). Since improved tests to diagnose Mtb infection are required, we studied the immune response to Mtb latency antigen Rv2626c in individuals exposed to the bacteria during different periods. Tuberculosis patients (TB), TB close contacts (CC: subjects exposed to Mtb for less than three months) and healthcare workers (HW: individuals exposed to Mtb at least two years) were recruited and QuantiFERON (QFT) assay, TST and ifn-γ secretion to Rv2626c were analyzed. Twenty-two percent of the individuals assessed had discordant results between QFT and TST tests. Furthermore, QFT negative and QFT positive individuals produced differential levels of IFN-γ against Rv2626c, in direct association with their exposure period to Mtb. Actually, 91% of CC QFT negative subjects secreted low levels of IFN-γ to Rv2626c, whereas 43% of HW QFT negative people produced elevated IFN-γ amounts against Rv2626c. Conversely, 69% of CC QFT positive subjects didn´t produce IFN-γ to Rv2626c. Interestingly, a similar pattern of IgG anti-Rv2626c plasma levels was observed. Therefore, determination of IFN-γ and igG levels against the dormancy antigen Rv2626c allows to identify established LTBI.

Differential Diagnosis of Latent Tuberculosis Infection and Active Tuberculosis: A Key to a Successful Tuberculosis Control Strategy

“…Furthermore, in patients with long-term LTBIs, higher percentages of IFN-γ + TNF-α + CD8 + T cells were found in response to Rv2031c protein in comparison with PPD − controls, with the most frequent memory phenotype of these cells being effector memory (CCR7 − CD45RA − ) T cells, followed by effector (CCR7 − CD45RA + ) T cells (Commandeur et al, 2011), which is consistent with an essential role of CD8 + T cells in defending the host from M. tuberculosis infection (Bruns et al, 2009). The Rv2626c antigen induced significantly higher levels of IFN-γ in QFT + individuals or healthy household contacts than in QFT − individuals or patients with TB and had the ability to differentiate individuals with LTBI from healthy controls and patients with TB, with 78.95% sensitivity and 83.02% specificity (Prabhavathi et al, 2015;Amiano et al, 2020), which is consistent with the sensitivity (77.1%) and specificity (85.1%) of Rv2626c reported in another study (Ashraf et al, 2014).…”

Study of CD27, CD38, HLA-DR and Ki-67 immune profiles for the characterization of active tuberculosis, latent infection and end of treatment

“…Other approaches for the characterization of this subset (e.g., measurement of other cytokines or multimeric tetramer staining) should be considered. And second, the immune status of each patient depends on multiple parameters, involving not only host and pathogen genetics but also the age of the host (Veneri et al, 2009), the length and type of antibiotic treatment and the recency of infection (Amiano et al, 2020), among others. Therefore, it is necessary to take into account the inherent heterogeneity of the patients when translating potential biomarkers into clinical applications.…”

Diagnóstico no bacteriológico de la tuberculosis. Indicadores de la respuesta inmune. Parte II

“…En nuestro país, en el Laboratorio de Inmunidad y Tuberculosis (IQUIBICEN, CONICET -UBA) se ha desarrollado un método diagnóstico de tipo IGRA (Diagnos-TB) similar a QuantiFERON pero mejorado por la inclusión de un tubo extra que permite la diferenciación de individuos LTBI de individuos sanos, pacientes con TB e individuos recientemente expuestos a M. tuberculosis, con una sensibilidad del 79% y una especificidad del 83%. 31 El mismo será ofrecido en un futuro próximo como Servicio Tecnológico de Alto Nivel (STAN -IQUIBICEN: www. iquibicen.fcen.uba.ar) para la comunidad a un costo netamente inferior al de las pruebas IGRA importadas.…”