Autoantibody Profiling of Cerebrospinal Fluid From Affective Disorders and Schizophrenia Patients by Phage Display: Method Optimization and Evaluation of Selected Autoantigens As Candidate Biomarkers

Abstract

Immunoproteomics approach applied on affective disorder and schizophrenia patient CSF samples yielded a number of candidate autoantigens. An overall analysis of those candidates revealed that impairment of myelination might have a role in etiology of such psychiatric disorders. Validations were based on phage ELISA that is applied on the most prominent autoantigen candidate obtained from phage display selection. In parallel, a conventional ELISA by recombinant peptide rather then purified phage, helped reproduce the results that imply a tendency of autoimmune reactivity in patient CSF samples compared to controls. Comparison of these results with the closest family members of the candidate protein mapping to the same N-terminal sequence revealed that, the sequence obtained by phage display is more antigenic than its homologues. Genomic expression profile of selected candidate and three other functionally related schizophrenia susceptibility genes were studied on mRNA in brain and spinal cord of mice, from postnatal day one until postnatal day forty-two. We could observe patterns of expression that may suggest a possible interplay of candidate proteins in the relevant neuronal maintenance mechanism. Our approach using cDNA phage display used in the identification of autoantigens in inflammatory and autoimmune diseases of the CNS is quite feasible despite several drawbacks like high false-positive number. Finally, our results may raise interest on myelination related proteins that may have roles in schizoaffective symptoms. However, strictly more effort has to be implemented to confirm and get more insight on our findings, for example developing mouse models and studying a broader range of serum and CSF samples