title: Differential recognition of microfilarial chitinase, a transmission-blocking vaccine candidate antigen, by sera from patients with Brugian and Bancroftian filariasis.
abstract: We examined the reactivity of human sera with recombinant microfilarial chitinase and with the antigenic determinant on the native parasite molecule identified by monoclonal antibody (MAb) MF1. In Brugian filariasis, the MF1 epitope is preferentially recognized by residents of endemic areas who remain amicrofilaremic and asymptomatic despite lifelong exposure to filarial worms. Reactivity with filarial chitinase and its MF1 epitope inversely correlates with microfilaremia levels in Bancroftian filariasis and is associated with a prolonged amicrofilaremic state following a single course of treatment with diethylcarbamazine. Chitinase does not appear to be a target of human antibodies that promote the adherence of cells to microfilariae, even though MAb MF1 itself promotes antibody-dependent, cell-mediated cytotoxic (ADCC) reactions that kill microfilariae in vitro. Such ADCC reactions are most often mediated by sera from amicrofilaremic patients with chronic elephantiasis that contain low or undetectable levels of IgG antibodies to chitinase. In contrast, antibodies to the MF1 epitope on this microfilarial stage-specific antigen are mostly present in amicrofilaremic donors without clinical lymphatic disease. These observations indicate that antibodies to the MF1 epitope of microfilarial chitinase reflect some degree of immune resistance to microfilaremia in a subgroup of patients with asymptomatic lymphatic filariasis. The amicrofilaremic state of individuals with chronic lymphatic disease appears to be mediated by reactivity to a different parasite antigen(s).
authors.affiliation: Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dissanayake
authors.forename: F B
authors.initials: FB
authors.lastname: Perler
authors.forename: M
authors.initials: M
authors.lastname: Xu
authors.forename: M W
authors.initials: MW
authors.lastname: Southworth
authors.forename: C K
authors.initials: CK
authors.lastname: Yee
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Dreyer
authors.forename: L
authors.initials: L
authors.lastname: Watawana
authors.forename: L
authors.initials: L
authors.lastname: Kurniawan
authors.forename: J A
authors.initials: JA
authors.lastname: Fuhrman
mesh_terms: D000328:Adult; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D000947:Antigens, Helminth / Q000276:immunology*; D017178:Brugia malayi / Q000201:enzymology / Q000276:immunology*; D002688:Chitinases / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005368:Filariasis / Q000276:immunology*; D006801:Humans; D008842:Microfilariae / Q000201:enzymology; D014958:Wuchereria bancrofti / Q000201:enzymology / Q000276:immunology*
chemical_list: D000947:Antigens, Helminth; D000939:Epitopes; D002688:Chitinases