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Exploring autoantibody signatures in brain tissue from patients with severe mental illness

Just, David (author)
KTH,Proteinvetenskap,Science for Life Laboratory, SciLifeLab,KTH Royal Inst Technol, SciLifeLab, Dept Prot Sci, Stockholm, Sweden.;Uppsala Univ, Dept Neurosci, Psychiat, Uppsala, Sweden.
Månberg, Anna, 1985- (author)
KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap,KTH Royal Inst Technol, SciLifeLab, Dept Prot Sci, Stockholm, Sweden.
Mitsios, Nicholas (author)
Karolinska Institutet
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Stockmeier, Craig A. (author)
Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA.
Rajkowska, Grazyna (author)
Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA.
Uhlén, Mathias (author)
KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap,KTH Royal Inst Technol, SciLifeLab, Dept Prot Sci, Stockholm, Sweden.;Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
Mulder, Jan (author)
Karolinska Institutet
Feuk, Lars (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab
Cunningham, Janet (author)
Uppsala universitet,Ekselius: Psykiatri
Nilsson, Peter (author)
KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik,KTH Royal Inst Technol, SciLifeLab, Dept Prot Sci, Stockholm, Sweden.
Carlström, Eva Lindholm (author)
Uppsala universitet,Medicinsk genetik och genomik
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 (creator_code:org_t)
2020-11-18
2020
English.
In: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 10:1
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • In recent years, studies have shown higher prevalence of autoantibodies in patients with schizophrenia compared to healthy individuals. This study applies an untargeted and a targeted affinity proteomics approach to explore and characterize the autoantibody repertoire in brain tissues from 73 subjects diagnosed with schizophrenia and 52 control subjects with no psychiatric or neurological disorders. Selected brain tissue lysates were first explored for IgG reactivity on planar microarrays composed of 11,520 protein fragments representing 10,820 unique proteins. Based on these results of ours and other previous studies of autoantibodies related to psychosis, we selected 226 fragments with an average length of 80 amino acids, representing 127 unique proteins. Tissue-based analysis of IgG reactivities using antigen suspension bead arrays was performed in a multiplex and parallel fashion for all 125 subjects. Among the detected autoantigens, higher IgG reactivity in subjects with schizophrenia, as compared to psychiatrically healthy subjects, was found against the glutamate ionotropic receptor NMDA type subunit 2D (anti-GluN2D). In a separate cohort with serum samples from 395 young adults with a wider spectrum of psychiatric disorders, higher levels of serum autoantibodies targeting GluN2D were found when compared to 102 control individuals. By further validating GluN2D and additional potential autoantigens, we will seek insights into how these are associated with severe mental illnesses.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)

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