Antibodies reactive to heat shock protein 90 induce oligodendrocyte precursor cell death in culture. Implications for demyelination in multiple sclerosis

  title={Antibodies reactive to heat shock protein 90 induce oligodendrocyte precursor cell death in culture. Implications for demyelination in multiple sclerosis},
  author={Cristina Cid and Jos{\'e} C. {\'A}lvarez-cerme{\~n}o and Emilio Camafeita and Matilde Salinas and Alberto Alc{\'a}zar},
  journal={The FASEB Journal},
Oligodendrocyte precursor cells (OPCs) are extremely efficient at remyelination. These cells persist in the adult human central nervous system and can proliferate. However, the failure to remyelinate is a pathological characteristic of the human demyelinating disease multiple sclerosis (MS), which suggests that these cells are ineffective in this disorder. This paper reports that IgG antibodies in the cerebrospinal fluid (CSF) of MS patients specifically recognize an antigen on OPCs in culture… 
Anti‐heat shock protein 90β antibodies decrease pre‐oligodendrocyte population in perinatal and adult cell cultures. Implications for remyelination in multiple sclerosis
These findings demonstrate, for the first time in vitro, a feasible mechanism to decrease the production of new oligodendrocytes, thus limiting the possibility of remyelination in multiple sclerosis.
Anti-heat shock protein 90β antibodies are detected in patients with multiple sclerosis during remission
Heat Shock Proteins in Multiple Sclerosis Pathogenesis: Friend or Foe?
Either positive or negative HSP role seems to depend on HSP family and on their intracellular or extracellular localization, so it will be interesting to study drug treatment which overexpress or inhibit HSP production in order to gain much more information about the role of the HSP in this disease.
Involvement of Cell Surface HSP90 in Cell Migration Reveals a Novel Role in the Developing Nervous System*
It is reported here that the two HSP90 isoforms, α and β, also localize on the surface of cells in the nervous system and are involved in their migration.
High cytotoxic sensitivity of the oligodendrocyte precursor cells to HSP90 inhibitors in cell cultures
Expression of heat shock protein 90 at the cell surface in human neuroblastoma cells
The first evidence of cell-surface Hsp90 expression in a cancer cell line from nervous tissue is described and may indicate a novel target for anti-tumoral agents.
Positive or Negative Involvement of Heat Shock Proteins in Multiple Sclerosis Pathogenesis: An Overview
This article reviews the current understanding of the involvement of the principal HSP families in MS and examines protective effects of HSPs in a variety of brain disease models.
Heat shock protein-90 beta is expressed at the surface of multipotential mesenchymal precursor cells: generation of a novel monoclonal antibody, STRO-4, with specificity for mesenchymal precursor cells from human and ovine tissues.
In addition to identifying an antibody reagent that identifies a highly conserved epitope expressed by MSCs from different species, this study points to a potential role for Hsp90beta in MSC biology.


Multiple sclerosis: altered expression of 70- and 27-kDa heat shock proteins in lesions and myelin.
White matter undergoing immune-mediated destruction in MS was associated with altered distribution and expression of HSC70 and HSP27, which may initially serve to protect myelin from further destruction and facilitate repair, but may subsequently present as additional immune targets involved in the progression of disease.
Differential expression of heat shock proteins by human glial cells
Autoreactive T and B cells responding to myelin proteolipid protein in multiple sclerosis and controls
A strong and persistent autoimmune response to PLP as well as to other myelin proteins, enriched in CSF, is proposed to be pathogenetically important in MS.
Patients with active relapsing‐remitting multiple sclerosis synthesize antibodies recognizing oligodendrocyte progenitor cell surface protein: Implications for remyelination
In myelinating cultures, cell lysis with antibody recognizing a progenitor cell–specific surface glycoprotein (AN2) suppressed the synthesis of myelin proteins and contributed to the development and progression of chronically demyelinated lesions.
Gamma delta T-cell receptor repertoire in acute multiple sclerosis lesions.
Evidence is provided for a role of gamma delta T cells in active stages of multiple sclerosis by quantitative immunohistochemistry and sequence analysis of T-cell antigen receptor (TCR) delta chains.
Anti-heat shock protein 70 kDa and 90 kDa antibodies in serum of patients with rheumatoid arthritis
IgGs to HSP 90 kDa are most common in longstanding RA patients with articular erosions, suggesting that they may be related to the articular prognosis in RA.
Pre-oligodendrocytes from adult human CNS
It is proposed that, in human demyelinating diseases such as multiple sclerosis, pre-oligodendrocytes may divide and/or migrate in response to signals present in demYelinated lesions and thus facilitate remyelination.
Microglial activation and amyloid‐β clearance induced by exogenous heat‐shock proteins
It is shown that heat‐shock proteins (HSPs), such as HSP90, HSP70, and HSP32, induce the production of interleukin 6 and tumor necrosis factor α and increase the phagocytosis and clearance of A β peptides, suggesting that microglial interaction with Aβ peptides is highly regulated by HSPs.
Oligodendrocytes and oligodendrocyte/type-2 astrocyte progenitor cells of adult rats are specifically susceptible to the lytic effects of complement in absence of antibody.
  • D. Wren, M. Noble
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1989
It is suggested that the susceptibility of oligodendrocytes and adult O/2A progenitor cells to complement-induced lysis, combined with other specific properties of adult O-2a progenitors, are consistent with--and may be a contributing factor--both in the generation of demyelinating lesions in multiple sclerosis and also in the failure of these lesions to be successfully repaired in adult multiple sclerosis patients.