Revisiting the Heterogeneous IFN-γ Response of Bacille of Calmette-Guérin (BCG)-Revaccinated Healthy Volunteers in a Randomized Controlled Trial: Effect of the Body Mass Index and of the IFNG+874 A/T Polymorphism

Abstract

In trials evaluating the immune responses to Bacille of Calmette-Guérin (BCG), the genetic background and the nutritional status are host-related factors that could affect the heterogeneity in these parameters. The IFNG+874 A/T (rs 62559044) polymorphism has been reported to influence the IFN-γ production by BCG-vaccinated individuals challenged in vitro with mycobacterial antigens. The body mass index (BMI) is a proxy for the nutritional status and has been associated both with the susceptibility to tuberculosis and with the IFN-γ response. We show that although the IFNG+874 A/T polymorphism was not associated with the heterogeneity of IFN-γ production in a randomized controlled trial that evaluated long-term immune responses to BCG revaccination previously conducted in Salvador, Bahia, Brazil, the effect of this polymorphism on the observed increase in IFN-γ production among revaccinated subjects was adjusted in individuals with a low BMI.

Interferon-gamma release assay performance in northeastern Brazil: influence of the IFNG+ 874 A>T polymorphism

“… 19 , 31 It has been suggested that other genetic factors may influence anti-mycobacterial IFN-γ production in Mtb infection/disease. 32 , 33 Despite the fact that two loci have recently been associated with IFN-γ production in response to ESAT-6 and BCG, the IFNG gene is not present in these regions. 34 …”

High-resolution quantitative proteomics applied to the study of the specific protein signature in the sputum and saliva of active tuberculosis patients and their infected and uninfected contacts

“…Remarkably, many individuals in close contact with an active TB patient do not become infected. Increasing evidence suggests that genetic heterogeneity of the host affects immune response to intracellular pathogens, such as mycobacteria (9)(10)(11). Innate immune response is the first line of defense and plays a key role in the quality, strength and efficacy of the adaptive immune response (12).…”

Host genetic background is a barrier to broadly effective vaccine–mediated protection against tuberculosis

“…SNPs in innate and adaptive immune-related genes alter BCG induced responses, such as those in the TLR2, 6, 10, and TOLLIP genes, which affect BCG-induced cytokine secretion ( 39 ). Polymorphisms in genes associated with TB susceptibility, such as NRAMP1, IFN-γ and IL-10 also influence responses to BCG ( 40 ). Within the CC mice, we also observed variation in BCG-mediated cytokine production following TB infection.…”

“…Glass slides were then digitized by Vanderbilt University Medical Center (Nashville, Tennessee, USA) and whole images generated using Aperio ScanScope at 400 times normal magnification with jpeg compression. Representative images were captured using Aperio ImageScope magnified 40 Univariate correlations. To evaluate how C57BL/6 mice, protected CC strains, and nonprotected CC strains compared in their relationships between lung cytokine production and Mtb burden, a series of univariate Pearson correlations were conducted.…”