The sporadic form of ALS is the most common form of MND and remains a syndrome of unproven etiology or etiologies. The application of increasingly sensitive immunocyto-chemical techniques to pathological specimens indicates the presence of a humoral and cellular immune response at the site of MN destruction. The magnitude of the response would seem to be quantitatively much less than that found in traditional inflammatory disorders such as multiple sclerosis. The similarity of the response in the autosomal dominant form of the disease, which can be reproduced in mice expressing the mutant SOD transgene, suggests that this response is at most a secondary event in the disease pathogenesis. This pattern of immune response seems rather parallel to that seen in other “neurodegenerative” disorders. Whether the disease-specific calcium channel antibody which correlates with disease progression also arises in response to tissue injury is not defined, although it is not reported in patients with MN destruction as a result of polio. The failure of even intense forms of immunotherapy to alter the disease course in ALS does further question the primary or secondary role of immune effector mechanisms to the disease process. One cannot exclude that individual cases, such as those arising on the background of lymphoma, may have a more significant immunopathogenesis and be akin to other paraneoplastic syndromes which affect different neuronal populations.
The LMN syndromes associated with IgM paraproteins and anti-GM1 antibodies would seem to be examples of motor neuropathies rather than primary neuronopathies, although the neuronotoxic effects of some of these antibodies are of note. Whether the markedly high titers of antibody found represent an intrinsic B cell derangement, as those cases associated with lymphoma or myeloma suggest, or a defect in T cell regulation of the B cell response together with persistent antigen stimulation remains to be resolved. GM1 is not usually considered as a potent antigen, although high-titer responses can be induced with appropriate immunization protocols . The clinical response of some of these cases to immunotherapy strengthens the hypothesis regarding the primary immune basis of the disorder. The inconsistency of the response remains, however, to be defined.
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Antel, J.P., Cashman, N.R. Immunological findings in amyotrophic lateral sclerosis. Springer Semin Immunopathol 17, 17–28 (1995). https://doi.org/10.1007/BF00194097
- Multiple Sclerosis
- Amyotrophic Lateral Sclerosis
- Paraneoplastic Syndrome
- Motor Neuropathy
- Immunization Protocol