Heat shock protein immunoreactivity in CSF

Abstract

The detection of raised immunoglobulin and the presence of oligoclonal bands (OCBs) on electrophoresis of multiple sclerosis (MS) CSF has been a useful diagnostic test, but a universal antigen to which these MS antibodies are directed has yet to be found. Potentially immunogenic heat shock proteins (HSPs) are preferential expressed in vitro in human oligodendrocytes compared with other glia, and in situ in oligodendrocytes found within the plaques of MS. Immunoreactivity directed against HSPs might therefore contribute to the immune-mediated demyelinating process found in MS. We examined this possibility by quantitatively (ELISA) measuring antibodies directed against a recombinant human HSP (HSP60) in CSF from 18 MS patients, and compared them with eight patients with acute disseminated encephalomyelitis, 12 with demyelinating peripheral neuropathies, and 59 with other neurologic diseases. Immunoblotting was used to confirm the specificity of the antibodies for binding to HSP60. We found a statistically significant correlation between antibody titers to HSP60 and the presence of OCBs in CSF. These results support the notion that HSP expression in the CNS, such as that observed in MS, may be immunogenic, leading to localized HSP antibody secretion. Such HSP-directed immunoreactivity could play a role in the pathogenesis of MS and other immune-mediated disorders of the nervous system.

A femtomolar-acting neuroprotective peptide.

“…Glial cells have been demonstrated to release several heat shock proteins, but not hsp 60 (51). However, hsp 60 immunoreactive material was found in the cerebrospinal fluid of patients with multiple sclerosis (52). Furthermore, changes in patterns of gene expression of intracellular stress proteins were found to be associated with neurodegeneration and neurodegenerative diseases (53).…”

Multiple Sclerosis

“…Therefore, specific autoantibodies as diagnostic markers in MS are not available yet. This is due to several reasons: the still unknown target antigen(s) within tbe CNS demyelinating [36] antibodies bound to their target might be a very local process and therefore, escape detection in the CSF antibody responses might be an unspecific immunological epiphenomenon after CNS tissue damage antibody responses directed against a large panel of antigens might comprise just a polyclonal, unspecific bystander activation phenomenon the heterogeneous disease complexity of MS finally, antibodies in multiple sclerosis may exert complex roles, including pathogenic, regulatory and reparative capacities.…”

Stress proteins: their role in the normal central nervous system and in disease states, especially multiple sclerosis

“…Initial studies of humoral immune responses to stress proteins in MS are mainly the work in our laboratory [3,4] and that of Freedman and his associates [56]. We used immunoblots to detect antibodies to native and recombinant mycobacterial stress proteins and to bacterial stress proteins in CSF and paired sera from persons with MS and OND.…”

“…When anti-stress protein antibodies were analyzed for isotypes, patients with MS had higher concentrations of antistress protein IgA antibodies than did OND patients. This suggested an in situ synthesis of such antibodies within the CNS in persons with MS. Prabhakar et al [56] studied antibody concentrations to recombinant hsp60 using an ELISA. Titers of antibodies in MS CSF were significantly higher than those seen in persons with OND, and the higher titers correlated with the presence of oligoclonal bands in MS CSF but not OND CSF.…”