Possible protective immunity in human opisthorchiasis

Chronic infections with the liver flukes Opisthorchis viverrini and Clonorchis sinensis affect over 30 million people in southeastern Asia. With ongoing exposure, reinfection readily occurs following curative treatment and cumulative infections result in significant morbidity and a predisposition to cholangiocarcinoma. Though protective immunity has never been described in human opisthorchiasis, heterogeneity in worm burden occurs and a small number of exposed residents of endemic areas remain apparently uninfected. To explore the nature of this heterogeneity, we compared levels of serum antibody (Ab) to O. viverrini measured by an enzyme-linked immunosorbent assay in 83 stool egg-positive and 49 stool egg-negative residents of an O. viverrini-endemic area in Thailand. Compared to the egg-positive residents, the egg-negative group had significantly higher levels of immunoglobulin (Ig)G, IgA and IgM to adult worm homogenate (AWH) and total Ab to metacercaria homogenate (MH). Furthermore, immunoblot analyses revealed that a significantly higher proportion of sera from the egg-negative residents had IgA reactivity against a 38-kDa AWH antigen and IgM reactivity against carbohydrate epitopes of a 42-kDa AWH glycoprotein antigen. These findings support a hypothesis that the egg-negative group includes individuals who may be immunologically resistant to this usually chronic infection.