Taenia Solium Metacestode Glycoproteins Diagnostic for Solitary Cysticercus Granuloma

Abstract

The aims of this thesis were: 1. To establish sensitive immunodiagnostic tests for solitary cysticercus granuloma. 2. To determine the prevalence of exposure to Taenia solium in the general population in India. 3. To understand the immune response that leads to establishment of solitary cyst infections in Indians. The specific objectives were: (1) To determine the biochemical structures of T solium metacestode glycoproteins that are infection specific and diagnostic for SCG. (2) To use these glycoproteins to establish sensitive and specific seroimmunodiagnostics for SCG. (3) To determine the seroprevalence of cysticercus antibodies in the general population of South India as an index of their exposure to T solium. (4) To determine Th1 and Th2 cytokine profiles of peripheral blood mononuclear cells, from patients with solitary NCC, multiple NCC and from healthy controls, stimulated with T solium infection specific glycoproteins. It was found on purification and structural characterization of 6 T solium metacestode specific glycoproteins with affinity for Lens culinaris that N-glycosylation and disulfide bonds of the proteins were essential for cysticercus antibody binding and the tertiary conformations of the proteins were optimal for antibody recognition. These properties of the antigenic cyst proteins enabled: 1. Serodiagnosis, in immunoblot format, suitable for detecting cysticercus antibodies in Indian patients with solitary cysticercus granuloma to be established. 2. The seroprevalence of cysticercosis in the general Indian population to be determined as 15.9%. 3. An understanding that immunity in the Indian patient with NCC may transit from early pro-inflammatory reactions that eliminate invasive oncospheres to anti-inflammatory responses that permit parasite to survive in the host. Strong inflammatory immune reactions may eliminate most of the large numbers of invasive oncospheres in T solium infections. A solitary cysticercus granuloma may arise from among a few ova that are not eliminated in these early reactions.