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Mensah, Gloria Ivy; Addo, Kennedy Kwasi; Tetteh, John Amissah; Sowah, Sandra; Löscher, Thomas; Geldmacher, Christof; Jackson-Sillah, Dolly (2014): Cytokine response to selected MTB antigens in Ghanaian TB patients, before and at 2 weeks of anti-TB therapy is characterized by high expression of IFN-gamma and Granzyme B and inter- individual variation. In: BMC Infectious Diseases 14:495


Background: There has been a long held belief that patients with drug-susceptible TB are non-infectious after two weeks of therapy. Recent microbiological and epidemiological evidence has challenged this dogma, however, the nature of the Mtb-specific cellular immune response during this period has not been adequately investigated. This knowledge could be exploited in the development of immunological biomarkers of early treatment response. Methods: Cellular response to four Mtb infection phase-dependent antigens, ESAT-6/CFP-10 fusion protein and three DosR encoded proteins (Rv1733c, Rv2029c, Rv2628) were evaluated in a Ghanaian TB cohort (n=20) before and after 2 weeks of anti TB therapy. After 6-days in vitro stimulation, Peripheral blood mononuclear cell (PBMC) culture supernatant was harvested and the concentration of IFN-gamma, Granzyme B, IL-10, IL-17, sIL2R alpha and TNF-alpha were determined in a 6-plex Luminex assay. Frequencies of IFN-gamma + CD4 and CD8 T cells were also determined in an intracellular cytokine assay. Results: All antigens induced higher levels of IFN-gamma, followed by Granzyme B, TNF-alpha and IL-17 and low levels of IL-10 and sIL-2R-alpha in PBMC before treatment and after 2 weeks of treatment. Median cytokine levels of IFN-gamma, Granzyme B, IL-17 and sIL-2R-alpha increased during week two, but it was significant for only Rv1733-specific production of Granzyme B (P = 0.013). The median frequency of antigen specific IFN-gamma + CD4 T cells increased at week two; however, only the increase in the ESAT-6/CFP-10-specific response was significant (P = 0.0008). In contrast, the median frequency of ESAT-6/CFP-10-specific IFN-gamma + CD8 T cell responses declined during week two (P = 0.0024). Additionally, wide inter-individual variation with three distinct patterns were observed; increase in all cytokine levels, decrease in all cytokine levels and fluctuating cytokine levels after 2 weeks of treatment. Conclusion: The second week of effective chemotherapy was characterized by a general increase in cytokine response to Mtb-specific antigens suggestive of an improvement in cellular response with therapy. However, the wide inter-individual variation observed would limit the utility of cytokine biomarkers during this period.