Studies characterizing 60 kda autoantibodies in subjects with schizophrenia.
BACKGROUND
Studies suggest that schizophrenic patients have an increased prevalence of serum antibodies to neuroblastoma cell proteins migrating at 60 kilodaltons (kDa). We present work identifying and characterizing 60 kDa antigen-antibody interactions.


METHODS
Sera from schizophrenic subjects and normal volunteers were screened by Western blotting. Proteins migrating at 60 kDa were characterized by two-dimensional gel electrophoresis and indirect immunofluorescent staining of human epithelial cell (HEp-2) slides. Human brain and bladder cell complementary deoxyribonucleic acid libraries were screened with immunoaffinity-purified antibodies. Complementary deoxyribonucleic acid clones were sequenced and compared with published databases. Proteins were generated by in vitro transcription/translation and expression in an Escherichia coli BL21 system. Immunoprecipitation and immunohistochemistry studies were performed.


RESULTS
Fifteen percent (17/117) of schizophrenic subjects and 3% (2/62) of normal volunteers had autoantibodies that reacted with 60 kDa proteins [chi(2)(1) = 4.4, p =.037]. Five percent of subjects had autoantibodies directed against 60 kDa heat shock protein (HSP60) [chi(2)(1) = 3.3, p =.100). Two-dimensional gel electrophoresis identified 13 different proteins migrating at 60 kDa; 5 were splice variants of HSP60, and 2 corresponded with a protein associated with MYC (PAM).


CONCLUSIONS
There is an increased prevalence of autoantibodies that bind to proteins migrating at 60 kDa in subjects with schizophrenia. Potential target antigens include HSP60 and PAM.
Wang
Xiao-Fen
XF
Department of Psychiatry, Veterans Affairs Medical Center, San Diego, California, USA.
Wang
Dunrui
D
Zhu
Weiguo
W
Delrahim
Katia K
KK
Dolnak
Douglas
D
Rapaport
Mark Hyman
MH
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000915:Antibody Affinity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002352:Carrier Proteins / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D018834:Chaperonin 60 / Q000378:metabolism; D003001:Cloning, Molecular; D039721:Diagnostic and Statistical Manual of Mental Disorders; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D015723:Gene Library; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases; D009447:Neuroblastoma / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D011994:Recombinant Proteins / Q000276:immunology; D012559:Schizophrenia / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases
D048868:Adaptor Proteins, Signal Transducing; D001323:Autoantibodies; D002352:Carrier Proteins; D018834:Chaperonin 60; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006899:Mixed Function Oxygenases; C114022:MYCBP2 protein, human; D044767:Ubiquitin-Protein Ligases