TIM-1 Polymorphisms and the Severity of Hepatitis A Virus Infection (Argentina)
The long term goal of this project is to understand the biology of Hepatitis A virus (HAV). Until recently, infection with HAV in industrialized countries was extremely common, occurring in greater than 98% of individuals. However, due to improved hygiene that has occurred over the past two decades in industrialized countries, the prevalence of infection with HAV has been greatly reduced, along with the potential benefits of infection, such as the prevention of asthma and allergy. Professor of Pediatrics Dr. Umetsu in conjunction with Dr. Rosenzweig, who directs the Laboratory of Investigation in Immunology at the Hospital Nacional de Pediatría J. P. Garrahan in Buenos Aires, are currently studying HAV infection in Argentina, since the prevalence of HAV infection in Argentina ranges from 31 to 80% depending on the geographic area, while the prevalence of infection with HAV in the US is <10%. The specific mechanisms by which HAV prevents the development of asthma and allergy are not known, but may be related to the HAV receptor, HAVcr1, also known as TIM-1, which has been shown by Dr. Umetsu to be a susceptibility gene for asthma and allergy. The research investigation will determine whether certain polymorphic variants of TIM-1 are associated with severe HAV infection, by studying a cohort of children in Argentina with a history of severe HAV infection and hepatic failure (70 children), and a control group of Argentinean children who have had mild/ unapparent infection with HAV (140 children). In this case control, cross-sectional, observational study, they will determine the relationship between severe HAV infection and TIM-1 genotype, determined by sequencing exon 4 of the TIM-1 gene, which contains all of the TIM-1 polymorphisms. This work is happening thanks to the support from a DRCLAS collaborative research grant awarded in the fall 2008 and the results examining the relationship between TIM-1 genotype and the severity of HAV infection will greatly enhance our understanding of HAV infection, will help to elucidate how TIM-1 polymorphisms affect the immune system, and how TIM-1 regulates the development of atopic diseases.
Participating Harvard faculty: Dale T. Umetsu, Prince Turki bin Abdul Aziz al-Saud Professor of Pediatrics, HMS Department of Pediatrics
Collaborators: Sergio Rosenzweig, Laboratory of Investigation in Immunology, Hospital Nacional de Pediatría J. P. Garrahan, Buenos Aires