CISH and Susceptibility to Infectious Diseases

Interleukin-2 is a proinflammatory interleukin with a pleiotropic effect on different cell types of the immune system. Cytokine-inducible SRC homology 2 (SH2) domain protein (CISH) is up-regulated by interleukin-2 and suppresses interleukin-2 signaling. This study shows that variants of the CISH gene are associated with susceptibility to bacteremia, malaria, and tuberculosis. This study shows that variants of the CISH gene are associated with susceptibility to bacteremia, malaria, and tuberculosis. Tuberculosis, malaria, and invasive bacterial disease together account for more than 5 million deaths annually in the developing world. Although a significant proportion of interindividual variation in disease susceptibility can be attributed to environmental factors such as malnutrition and infection with the human immunodeficiency virus (HIV), a substantial portion is unexplained. Comparative studies involving twins and adopted persons suggest a genetic component, 1 and genes that, when mutated, result in primary immunodeficiency states have been identified. Such immunodeficiencies are extremely rare, however, and the current understanding of common host genetic factors influencing susceptibility to major infectious diseases at the population level . . .