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Individual Susceptibility to Infection

A recent study explored the genetics of susceptibility to infectious diseases (NEJM 2010;362:2092-2101). Inflammatory cytokine production is the host immune response to infection by many pathogens including bacteria, mycobacteria, and malaria. The CISH gene codes for cytokine-inducible SRC homology 2 domain protein (CISH) which controls cytokine signaling, in particular interleukin-2. Interleukin-2 is critical to immunity in that it mediates T-cell response, proliferation of B cells and natural killer cells, and promotes maturation of macrophages.Researchers analyzed data on 8402 persons from Kenya, Malawi, Hong Kong, Gambia, and Vietnam with various infections including bacteremia, tuberculosis, and malaria. Peripheral blood samples were collected for CISH gene sequencing and SNP (single nucleotide polymorphism) analysis. There were 5 CISH SNPs identified that conferred increased susceptibility to bacterial, mycobacterial and malarial infections. The overall risk of infection was increased by 18% in those carrying a single SNP, and by 81% in those with 4 or more risk alleles.This study indicates that genetic factors in addition to environmental factors, such as malnutrition and HIV disease, are responsible for individual susceptibility to infection. Future clinical management of infectious diseases may include alterations of genetic pathways in addition to antimicrobial agents.

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