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 [χ2(1) = 4.4, p = .037]. Five percent of subjects had autoantibodies directed against 60 kDa heat shock protein (HSP60) [χ2(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.