Advances in understanding and treatment of immune‐mediated disorders of the peripheral nervous system

Abstract

During recent years, novel insights in basic immunology and advances in biotechnology have contributed to an increased understanding of the pathogenetic mechanisms of immune-mediated disorders of the peripheral nervous system. This increased knowledge has an impact on the management of patients with this class of disorders. Current advances are outlined and their implication for therapeutic approaches addressed. As a prototypic immune-mediated neuropathy, special emphasis is placed on the pathogenesis and treatment of the Guillain-Barré syndrome and its variants. Moreover, neuropathies of the chronic inflammatory demyelinating, multifocal motor, and nonsystemic vasculitic types are discussed. This review summarizes recent progress with currently available therapies and--on the basis of present immunopathogenetic concepts--outlines future treatment strategies.

Guillain-Barré syndrome following thoracic spinal cord trauma

“…1 Myelin proteins P0, P2, and PMP22 have been shown in humans to induce a CD4 T-cell attack of the endoneurium, leading to demyelination. 12 Exposure to other antigens, including glycolipids (galactocerebroside) and gangliosides (GM1, GD1), has also been shown to cause a demyelinating neuropathy. 13 Trauma, itself, can alter immune function.…”

Biological Agents for Chronic Inflammatory Demyelinating Polyradiculoneuropathy

“…6,7,30 Natalizumab Natalizumab (Tysabri®) is a monoclonal antibody (mAb) targeted at the α4 subunit of α4β1 (VLA4) and α4β7 integrins that are expressed on…”

“…4 The pathogenesis of CIDP is not fully understood. 1,6,7 Cell-mediated and/or humoral immune mechanisms are involved in an attack against unidentified target antigen(s) of the myelin sheath and/or Schwann cells, at times leading also to secondary axonal injury.…”

Recent Advances in the Treatment of Neurological Autoimmune Disorders

“…There were also detectable levels of IgG and complement deposition in the nerves (Hafer-Macko et al, 1996). The distinct involvement of T and B-cells are identified in few subtypes, with the activated complement system playing a prime role in mediating demyelination and impaired conduction but still understanding the pathology of GBS remains rather elusive (Kieseier et al, 2004). The treatment for GBS is often confined to the immunomodulatory therapy where plasmapheresis and intravenous administration of immunoglobulin's IVIg are given the priority (Dalakas, 1999;Hadden et al, 1998).…”

“…Polyneuropathies are divided into 3 subtypes as chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN) and IgM anti-myelinassociated glycoprotein (MAG) demyelinating neuropathy (Kornberg & Pestronk, 2003;Czaplinski & Steck, 2004;Kieseier et al, 2004). Both the T and B-cell mediated immune havoc is noticed in CIDP with the majority of antibodies directed towards the glycolipids GM1 (Yan et al, 2000).…”