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Untargeted screening for novel autoantibodies with prognostic value in first-episode psychosis
KTH Royal Inst Technol, Sch Biotechnol, Affin Prote, SciLifeLab, Tomtebodavagen 23A, S-17165 Stockholm, Sweden..
Karolinska Inst, Ctr Mol Med, Karolinska Univ Hosp Solna, Dept Clin Neurosci, L8 01, Stockholm, Sweden.;Karolinska Univ Hosp Solna, SLSO, Psykiatri Nordvast, Stockholm, Sweden.;Karolinska Inst, Karolinska Univ Hosp Solna, Ctr Pharmacoepidemiol, Dept Med, Stockholm, Sweden..
Karolinska Inst, Ctr Mol Med, Karolinska Univ Hosp Solna, Dept Clin Neurosci, L8 01, Stockholm, Sweden..
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
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2017 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 7, article id e1177Article in journal (Refereed) Published
Abstract [en]

Immunological and inflammatory reactions have been suggested to have a role in the development of schizophrenia, a hypothesis that has recently been supported by genetic data. The aim of our study was to perform an unbiased search for autoantibodies in patients with a first psychotic episode, and to explore the association between any seroreactivity and the development of a Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) disorder characterized by chronic or relapsing psychotic symptoms. We collected plasma samples from 53 patients when they were treated for their first-episode psychosis, and 41 non-psychotic controls, after which the patients were followed for a mean duration of 7 years. Thirty patients were diagnosed with schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder or a long-term unspecified nonorganic psychosis during follow-up, whereas 23 patients achieved complete remission. At the end of follow-up, plasma samples were analyzed for IgG reactivity to 2304 fragments of human proteins using a multiplexed affinity proteomic technique. Eight patient samples showed autoreactivity to the N-terminal fragment of the PAGE (P antigen) protein family (PAGE2B/PAGE2/PAGE5), whereas no such autoreactivity was seen among the controls. PAGE autoreactivity was associated with a significantly increased risk of being diagnosed with schizophrenia during follow-up (odds ratio 6.7, relative risk 4.6). An immunohistochemistry analysis using antisera raised against the N-terminal fragment stained an unknown extracellular target in human cortical brain tissue. Our findings suggest that autoreactivity to the N-terminal portion of the PAGE protein family is associated with schizophrenia in a subset of patients with first-episode psychosis.

Place, publisher, year, edition, pages
2017. Vol. 7, article id e1177
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:uu:diva-333523DOI: 10.1038/tp.2017.160ISI: 000406715200003OAI: oai:DiVA.org:uu-333523DiVA, id: diva2:1157303
Funder
EU, FP7, Seventh Framework Programme, FP7-PEOPLE-2013-ITN-607616Swedish Research Council, 521-2014-3857
Available from: 2017-11-15 Created: 2017-11-15 Last updated: 2017-11-29Bibliographically approved

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