Identification of antibodies to heat shock proteins 90 kDa and 70 kDa in patients with schizophrenia

Objectives: Recent reports of antibodies to heat shock proteins 60 kDa (HSP60) and HSP70 suggested that antibodies to the heat shock protein that plays a protective role against environmental stresses in a cell might be related to the pathogenesis of schizophrenia, although the antibody to HSP90 had not yet been identified in patients with schizophrenia. In this study, we tried to elucidate the specific involvement of the autoimmunity to HSPs in the pathogenesis and development of schizophrenia. Methods: Antibodies to HSP90 and HSP70 in 90 patients with schizophrenia and in 83 normal controls were measured by enzyme-linked immunosorbent assay (ELISA) coupled with the avidin-biotin system. In the patients, the association between antibody levels and clinical variables were sought. In addition, changes in antibody levels after treatment with antipsychotic medication were investigated. Results: Eighteen (20.0%) of the 90 patients showed 'high' levels of antibody to HSP90 above a cutoff value, and 28 (31.1%) of those showed 'high' antibody levels to HSP70. On the other hand, only four (4.8%) of the normal controls showed 'high' HSP90 antibody levels, and one (1.2%) of these showed 'high' antibody level to HSP70. The distribution of elevated HSP90 antibody was significantly associated with that of elevated HSP70 antibody in the patients with schizophrenia. The patients with 'high' levels of antibody to HSP70 showed higher initial Brief Psychiatric Rating Scale (BPRS) scores and showed greater clinical improvement than those with 'low' levels, while the patients with 'high' levels of antibody to HSP90 did not. The frequency of patients with high levels of antibody to HSP70 was decreased significantly after 6 weeks of antipsychotic treatment, while the frequency of patients with high levels of antibody to HSP90 was not. Conclusions: Our results presented the presence of abnormal immune reactivity involving antibody to HSP90 and antibody to HSP70 in a subset of patients with schizophrenia. Differential patterns of distribution, of the association with clinical symptom severity, and of the changes of levels with treatment suggested the possibility that these two antibodies might be involved specifically in the pathogenesis of schizophrenia.