Elevated Cellular Immune Response to Human Heat-Shock Protein-60 in Schizophrenic Patients

Abstract

Heat shock protein-60 (HSP60) is implicated in several autoimmune diseases as a triggering antigen. Based on the autoimmune hypothesis of schizophrenia, we examined cellular and humoral responses against HSP60 and a series of its peptide fragments with peripheral blood samples of schizophrenic patients and healthy subjects each of group size between 12 to 32 participants. The average stimulation indices of peripheral blood mononuclear cells (PBMC) to HSP60 were 3.17 +/- 0.36 (mean +/- SE) for schizophrenic patients and 2.23 +/- 0.24 (mean +/- SE) for healthy subjects, with a significant difference between the groups (P = 0.0457). In parallel, 38 synthetic peptide fragments of HSP60, each of 18-21 amino acids, were tested for in vitro sensitization of PBMC. With one peptide (p32) the average stimulation index of PBMC from schizophrenic patients was significantly higher than that obtained for PBMC of control subjects (P = 0.0006). Comparing the cellular immune response to p32 between patients who were distinctive responders (n = 10) or non-responders (n = 10) to neuroleptic treatment indicated a similar elevation of cellular response in these groups. Antibodies against HSP60 were screened by dot-blot and ELISA in the sera of the above blood samples. Titers of IgG and IgM against HSP60 were found to be of similar magnitude in schizophrenic patients and in controls. Titers of IgA against HSP60 were somewhat higher in the sera of schizophrenic patients in comparison to sera of control subjects (P = 0.0605).

nflammation and damage-associated molecular patterns in major psychiatric disorders

“…16 Various intracellular DAMPs are released from the mitochondria, the autophagosome, the endoplasmic reticulum, the nucleus, and the cytosol.7,16 A variety of stressful situations including environmental, pathological, or physiological stimuli induce a marked increase in HSPs synthesis, which are leaked into the extracellular compartment and activate immune signaling pathways.7,37 HSPs are considered tissue alarmins and can also act as DAMPs by interacting with toll-like receptors (TLRs). 19,20 These molecules trigger innate immune responses by inducing the release of cytokines and chemokines and activating natural killer cells. 19 Likewise, extracellular S100 proteins influence innate and adaptive immune responses by their wide-ranging regulatory role on macrophages, monocytes, neutrophils, lymphocytes, microglia, mast cells, and vascular smooth muscle cells.7,38 These proteins have been considered as a marker of brain injury in several pathologies.…”

“…19,20 These molecules trigger innate immune responses by inducing the release of cytokines and chemokines and activating natural killer cells. 19 Likewise, extracellular S100 proteins influence innate and adaptive immune responses by their wide-ranging regulatory role on macrophages, monocytes, neutrophils, lymphocytes, microglia, mast cells, and vascular smooth muscle cells.7,38 These proteins have been considered as a marker of brain injury in several pathologies. 21 Our study evaluated HSP70, HSP60 and S100B serum levels among different psychiatric disorders.…”

Biologische Hypothesen zur Schizophrenie: Mögliche Einflüsse von Immunologie und Endokrinologie

“…Da die Befunde sehr inhomogen sind, ist ihre Bedeutung für die ätiologische Forschung unklar. Etwas homogenere Untersu− chungsergebnisse weisen Studien zu unspezifischen Antikörpern wie ¹heat shock proteins" [17,18] und löslichen interzellulären Adhäsionsmolekülen, z. B. sICAM [19] auf.…”