Boosting effect of IL-7 in interferon gamma release assays to diagnose Mycobacterium tuberculosis infection

Abstract

BackgroundA quarter of the world’s population is estimated to be infected with Myobacterium tuberculosis (Mtb). Infection is detected by immune response to M. tuberculosis antigens using either tuberculin skin test (TST) and interferon gamma release (IGRA’s), tests which have low sensitivity in immunocompromised. IL-7 is an important cytokine for T-cell function with potential to augment cytokine release in in-vitro assays. This study aimed to determine whether the addition of IL-7 in interferon-gamma release assays (IGRAs) improves its diagnostic performance of Mtb infection.Methods44 cases with confirmed TB and 45 household contacts without TB were recruited and 1ml of blood was stimulated in two separate IGRA’s tube set: one set of standard Quantiferon TB gold tubes mitogen, TB antigen and TB Nil; one set of customized Quantiferon TB gold tubes with added IL-7. Following IFN-γ and IP-10 release was determined using ELISA.ResultsWe found that the addition of IL-7 led to significantly higher release of IFN-γ in individuals with active TB from 4.2IU/ml (IQR 1.4–6.9IU/ml) to 5.1IU/ml (IQR 1.5–8.1IU/ml, p = 0.0057), and we found an indication of a lower release of both IFN-γ and IP-10 in participants with negative tests.ConclusionsIn TB cases addition of IL-7 in IGRA tubes augments IFN-γ but not IP-10 release, and seems to lower the response in controls. Whether IL-7 boosted IGRA holds potential over standard IGRA needs to be confirmed in larger studies in high and low TB incidence countries.

Expression of ESAT‐6 antigen from Mycobacterium tuberculosis in broccoli: An edible plant

“…It is proposed that for vaccine development against TB, targeting those antigens that are highly expressed during early M. tuberculosis infection such as ESAT‐6 and CFP10, will have an advantage in inducing an effective immune response . Additionally, the ESAT‐6 antigen has great potential in provoking IFN‐γ stimulation .…”

“…6 kDa early secretory antigenic target (ESAT‐6) is one of the most important subunit vaccine antigen of MTB, which is encoded in the region of deletion (RD‐1) in all strains of MTB except in the BCG vaccine strains . ESAT‐6 is also responsible for synthesis of gamma interferon (IFN‐γ), which is a marker for protective immune response with protective immunity comparable to BCG . Hence, ESAT‐6 could prove to be one of the most indispensable components as a subunit vaccine candidate to prevent TB.…”

Borrelia burgdorferi Is a Poor Inducer of Gamma Interferon: Amplification Induced by Interleukin-12

“…To optimize IFN-g production capacity of PBMCs after B. burgdorferi exposure in vitro, IL-7 in combination with IL-12 and B. burgdorferi was used to stimulate PBMCs thawed from liquid nitrogen. IL-7 is a wellknown T-cell growth factor and acts synergistically with IL-12 (40)(41)(42)(43). IL-7 mRNA of PBMCs was enhanced upon B. burgdorferi stimulation in healthy volunteers, and IL-7 mRNA was slightly upregulated in LB patients 3 weeks after infection (Fig.…”

Diagnosis for Latent Tuberculosis Infection: New Alternatives

“…Similar to what has been described for TST, the performance of the IGRA tests can be affected by several factors, mainly related to an impaired immune response and to technical issues. For example, the addition of IL-7 increases test positivity ( 36 ). The clinical accuracy of IGRAs seems to be negatively affected in patients with immune-mediated inflammatory diseases (IMIDs) ( 37 ) such as Crohn's disease, where the function of immune cells is suppressed ( 38 ), as well as in patients on immunomodulatory drugs such as teriflunomide, which exerts an inhibitory effect on T-cell activation, and outcome in QuantiFERON results changing from positive to negative with marked reduction in IFN-γ ( 39 ).…”