Molecular Mimicry Between Toxoplasma gondii B-Cell Epitopes and Human Antigens Related to Schizophrenia: An In Silico Approach

TL;DR

This study explores how proteins from the Toxoplasma gondii parasite might resemble human proteins linked to schizophrenia, suggesting a possible immune-based mechanism for the disorder.

Contribution

The study identifies potential molecular mimicry between Toxoplasma gondii proteins and schizophrenia-related autoantigens using in silico methods.

Findings

Five schizophrenia-related autoantigens showed similarities with Toxoplasma gondii proteins.

Gamma-enolase (ENO2) exhibited the highest homology with T. gondii proteins, up to 65% identity.

Shared antigenic features suggest a possible autoimmune mechanism linking T. gondii infection to schizophrenia.

Abstract

Schizophrenia is a complex disorder influenced by genetic, neurobiological, and environmental factors, with increasing evidence implicating immune dysregulation. This study examined potential molecular mimicry between autoantigens associated with schizophrenia and proteins from Toxoplasma gondii, a parasite previously linked to the disorder. Amino acid sequences of schizophrenia-related autoantigens were retrieved from databases (AAgAtlas, PubMed), and homologous sequences were searched within the T. gondii proteome. Sequence identity was evaluated, and conserved B-cell epitopes were predicted using three-dimensional structures from the Protein Data Bank or models generated in Swiss-Model, followed by epitope mapping with ElliPro. Five autoantigens—gamma-enolase (ENO2), thyroid peroxidase (TPO), glutamic acid decarboxylase 65 kDa isoform (GAD65), serine/threonine-protein kinase 2 (VRK2), and dihydropyrimidine dehydrogenase [NADP(+)] (DPYD)—showed similarities with T. gondii proteins. Among them, enolase exhibited the highest homology, with identities up to 65%. These findings provide preliminary evidence of shared antigenic features between the parasite and schizophrenia-related autoantigens. Such mimicry could contribute to disease mechanisms by triggering autoimmune responses in genetically susceptible individuals, supporting the hypothesis that T. gondii infection may influence schizophrenia pathogenesis. Nonetheless, the results are based exclusively on in silico analyses, and experimental validation will be required to confirm potential cross-reactivity.

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