The most common autoimmune neuropathies include the
acute inflammatory polyneuropathy [the
Guillain-Barré Syndrome(s)]; chronic inflammatory demyelinating
polyneuropathy (
CIDP), multifocal motor neuropathy (MMN) and
IgM anti-MAG-antibody mediated paraproteinemic neuropathy. These neuropathies occur when immunologic tolerance to peripheral nerve components (myelin, Schwann cell, axon, and motor or ganglionic neurons) is lost. Based on the immunopathologic similarities with
experimental allergic neuritis induced after immunization with nerve
proteins, disease transfer experiments with the patients' serum or with intraneural
injections, and immunocytochemical studies on the patients' nerves, it appears that both cellular and humoral factors, either independently or in concert with each other, play a role in the cause of these neuropathies. Although in some of them there is direct evidence for autoimmune reactivity mediated by specific
antibodies or autoreactive T lymphocytes, in others the underlying immune-mediated mechanisms have not been fully elucidated, in spite of good response to
immunotherapies. The review highlights the factors associated with breaking the T-cell tolerance, the T-cell activation and costimulatory molecules, the immunoregulatory T-cells and relevant
cytokines and the
antibodies against peripheral nerve
glycolipids or
glycoproteins that seem to be of pathogenic relevance.
Antigens in the nodal, paranodal and juxtaparanodal regions are discussed as potentially critical targets in explaining conduction failure and rapid recovery. Based on the immunopathologic network believed to play a fundamental role in the pathogenesis of these neuropathies, future therapeutic directions are highlighted using new
biological agents against T-cells,
cytokines, B-cells, transmigration and transduction molecules.