CISH and susceptibility to infectious diseases

Area of Science:

• Immunology
• Genetics
• Infectious Diseases

Background:

• The interleukin-2 (IL-2) immune response is vital for fighting infections.
• Cytokine-inducible SH2-containing protein (CISH) regulates IL-2 signaling and acts as a suppressor of cytokine signaling.

Purpose of the Study:

• To investigate the association between CISH gene polymorphisms and susceptibility to major infectious diseases.
• To determine the role of CISH in host defense against pathogens.

Main Methods:

• A case-control study design was employed.
• Analyzed blood samples from 8402 individuals across Gambia, Hong Kong, Kenya, Malawi, and Vietnam.
• Examined CISH polymorphisms, including single-nucleotide polymorphisms (SNPs) at specific positions, and their association with disease susceptibility.

Main Results:

• Significant associations were found between CISH variant alleles and increased susceptibility to bacteremia, tuberculosis, and malaria.
• A combined analysis of five CISH SNPs showed a strong association with these infectious diseases (P=3.8x10(-11)).
• The -292 CISH polymorphism was a major contributor to this association (P=4.58x10(-7)), with carriers exhibiting reduced IL-2-induced CISH expression (25-40% less).

Conclusions:

• CISH gene variants are associated with susceptibility to a range of infectious diseases.
• Negative regulators of cytokine signaling, like CISH, play a significant role in immunity against diverse pathogens.
• Individuals with variant CISH alleles had an at least 18% increased risk of developing these infectious diseases.