Association of Antibodies to Helminth Defense Molecule 1 With Inflammation, Organomegaly, and Decreased Nutritional Status in Schistosomiasis Japonica

Abstract Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune responses. Using a whole-proteome differential screening method, we identified Schistosoma japonicum helminth defense molecule 1 (SjHDM-1) as a target of antibodies expressed by S. japonicum–resistant but not S. japonicum–susceptible individuals. In a longitudinal cohort study (n = 644) conducted in a S. japonicum–endemic region of the Philippines, antibody levels to SjHDM-1 did not predict resistance to reinfection but were associated with increased measures of inflammation. Individuals with high levels of anti–SjHDM-1 immunoglobulin G had higher levels of C-reactive protein than those with low anti–SjHDM-1. High anti–SjHDM-1 immunoglobulin G responses were also associated with reduced biomarkers of nutritional status (albumin), as well as decreased anthropometric measures of nutritional status (weight-for-age and height-for-age z scores) and increased measures of hepatomegaly. Our results suggest that anti–SjHDM-1 responses inhibit the immunomodulatory function of SjHDM-1, resulting in increased morbidity rates. Antibodies targeting the immunomodulator Schistosoma japonicum helminth defense molecule 1 (SjHDM-1) are associated with increased inflammation, hepatomegaly, and multiple measures of reduced nutritional status. Our results suggest that anti–SjHDM-1 responses inhibit the beneficial immunomodulatory function of SjHDM-1, resulting in host morbidity.