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

• Published in: The Journal of infectious diseases 2024-10, Vol.230 (4), p.1023-1032
• Main Authors: Ruiz, Amanda E, Pond-Tor, Sunthorn, Stuart, Ronald, Acosta, Luz P, Coutinho, Hannah M, Leenstra, Tjalling, Fisher, Sydney, Fahey, Owen, McDonald, Emily A, Jiz, Mario A, Olveda, Remigio M, McGarvey, Stephen T, Friedman, Jennifer F, Wu, Hannah Wei, Kurtis, Jonathan D
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Animals; Antibodies, Helminth - blood; Antibodies, Helminth - immunology; C-reactive protein; Child; Female; Helminth Proteins - immunology; Hepatomegaly - immunology; Humans; Immune response; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulins; Immunomodulation; Inflammation; Inflammation - immunology; Longitudinal Studies; Male; Middle Aged; Morbidity; Nutritional Status; Philippines - epidemiology; Proteomes; Schistosoma japonicum - immunology; Schistosomiasis; Schistosomiasis japonica - immunology; Young Adult
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiae330

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.