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

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 <i>Toxoplasma gondii</i>, 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 <i>T. gondii</i> 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 (<i>ENO2</i>), thyroid peroxidase (<i>TPO</i>), glutamic acid decarboxylase 65 kDa isoform (<i>GAD65</i>), serine/threonine-protein kinase 2 (<i>VRK2</i>), and dihydropyrimidine dehydrogenase [NADP(+)] (<i>DPYD</i>)-showed similarities with <i>T. gondii</i> 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 <i>T. gondii</i> 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.