Abstract:
Schistosome infection is a major public health concern affecting millions of people living in tropical regions of Africa, Asia, and
South America. Schistosomes cause mild clinical symptoms in most subjects, whereas a small proportion of individuals presents
severe clinical disease (as periportal fibrosis (PPF)) that may lead to death. Severe PPF results from an abnormal deposition of
extracellular matrix proteins in the periportal spaces due to a chronic inflammation triggered by eggs and schistosome Ags.
Extracellular matrix protein production is regulated by a number of cytokines, including IFN- . We have now screened putative
polymorphic sites within this gene in a population living in an endemic area for Schistosoma mansoni. Two polymorphisms located
in the third intron of the IFN- gene are associated with PPF. The IFN- 2109 A/G polymorphism is associated with a higher
risk for developing PPF, whereas the IFN- 3810 G/A polymorphism is associated with less PPF. The polymorphisms result in
changes in nuclear protein interactions with the intronic regions of the gene, suggesting that they may modify IFN- mRNA
expression. These results are consistent with the results of previous studies. Indeed, PPF is controlled by a major locus located on
chromosome 6q22-q23, closely linked to the gene encoding the -chain of the IFN- receptor, and low IFN- producers have been
shown to have an increased risk of severe PPF. Together, these observations support the view that IFN- expression and subsequent
signal transduction play a critical role in the control of PPF in human hepatic schistosome infection (S. mansoni). The
Journal of Immunology, 2003, 171: 5596–5601.
