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Oligoclonal bands in multiple sclerosis; Functional significance and therapeutic implications. Does the specificity matter?

      Highlights

      • Immunoglobulins in oligoclonal bands secreted by plasma cells in the CNS can contribute to worsening pathology in MS.
      • Secreted immunoglobulin can interact with microglial Fc receptors in an antigen non-specific manner.
      • Microglia and astrocytes may create a survival niche for long-term plasma cell survival.
      • Plasma cells, microglia and astrocytes may interact to establish a locally neurotoxic or dystrophic environment.
      • Bruton's tyrosine kinase inhibitors may be therapeutic agents for the potential elimination of plasma cells and OCB from the CNS in MS.

      Abstract

      Since their discovery, the existence of secreted oligoclonal immunoglobulin in the central nervous system in people with multiple sclerosis has been the subject of scientific investigation and debate over several decades. Although autoantibodies can be detected in some individuals, probably secondary to release of neo-antigens after damage, evidence for a major, primary involvement of damaging antibodies is still relatively lacking. However, it is possible to construct a working hypothesis that establishes the interaction of plasma cells, which are the source of oligoclonal bands, microglia and astrocytes to create a self-perpetuating activated phenotype. This may generate an environment conducive to long-term plasma cell survival and the initiation and perpetuation of neurotoxicity that may contribute to disease worsening in multiple sclerosis. Therapeutic strategies to re-establish a homeostatic environment conducive to repair/recovery are indicated to control progressive multiple sclerosis.

      Keywords

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