Molecular Mimicry Drives Locally Produced Autoantibodies in Subarachnoid Neurocysticercosis

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Abstract Background Subarachnoid neurocysticercosis (SANCC) is a condition manifested by chronic meningitis induced by infection with Taenia solium. We sought to determine if there is evidence of autoantibody production in SANCC and whether local production of autoantibodies could be driven by immunogenic homologues found in T. solium. Methods Reactivity of pooled cerebral spinal fluid (CSF) from SANCC patients and uninfected controls was screened against a human proteome chip. Serum from 27 SANCC patients was then tested for antibodies to the 15 top screen hits using a Luciferase ImmunoPrecipitation System (LIPS). Eight human proteins were further tested using CSF from SANCC and controls. In parallel, Taenia homologues were expressed and screened using LIPS. Antibodies directed at the 2 proteins with significant reactivity were then used to probe Taenia crassiceps crude antigen using a 2D immunoblot. Reactive proteins were subjected to mass spectroscopy for identification. Results Significant immunoglobulin G reactivity was seen in the CSF of SANCC compared with uninfected controls to both human annexin A8 (ANXA8) and chromatin complexes subunit BAP18 (BAP18) and their T. solium homologues on LIPS testing. 2D-separated Taenia crassiceps soluble antigen was probed with either antihuman-ANXA8 or antihuman BAP18 antibodies in immunoblotting. The antihuman ANXA8 antibody identified T. solium annexin B3 (GenBank: AAY27744.1), whereas the antihuman BAP18 antibody identified cestode enzymes involved in metabolic pathways. Conclusions Taenia-derived annexin and metabolic enzymes contain epitopes that likely drive local CSF antibody production that cross-reacts with human ANXA8 and BAP18 and may contribute to the pathology underlying SANCC.

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