IgM deposits at nodes of ranvier in a patient with amyotrophic lateral sclerosis, anti‐GM1 antibodies, and multifocal motor conduction block

Abstract

We studied a patient with amyotrophic lateral sclerosis, multifocal motor conduction block, and IgM anti-GM1 antibodies. A sural nerve biopsy demonstrated deposits of IgM at nodes of Ranvier by direct immunofluorescence. The deposits were granular and located in the nodal gap between adjacent myelin internodes, and in some instances, they extended along the surface of the paranodal myelin sheath. When injected into rat sciatic nerve, the serum IgM bound to the nodes of Ranvier, and the binding activity was removed by preincubation with GM1. These observations suggest that anti-GM1 antibodies may have caused motor dysfunction by binding to the nodal and paranodal regions of peripheral nerve.

Association of severe myoclonic epilepsy of infancy (SMEI) with probable autoimmune lymphoproliferative syndrome-variant

“…48,50 Therefore, some Authors advise to investigate the same target protein for genetic and autoimmune diseases, because similar symptoms may be due to mutation and to autoantibodies targeting the same protein. 50 In our case, the association of epilepsy with non-organ specific ANA and antimicrosomal organspecific autoantibodies, dysphagia, abnormalities of peripheral sensory-motor nerve conduction, bilateral leg pain and hyperreflexia, atonia, and EMG abnormalities suggest a role of autoantibodies against the Na + ion channels 50,52,53 acting on the surface of neurons, with consequent slow inactivation 15,54 which results in epileptiform activity in mammalian brain 52,53 and conduction block in peripheral nerve. 56 The identification of SCN1A mutation involving Na + channels in SMEI and GEFS + suggests that an autoimmune attack to the mutated Na + channels, recognized as non-self by the organism, may be present in some cases of SMEI, as reported in other epilepsies.…”

Application of Liposome Immune Lysis Assay for Studies on Anti-Ganglioside Antibodies.

“…The latter assay seems more relevant in that this membrane lysis may be related to the phenomena observed during the disease process. This view is supported by the fact that complement was found along with IgM deposits at the nodes of Ranvier in a sural nerve biopsy specimen from an ALS patient [14]. Thus LILA may be able to detect the elevation of anti-GM 1 antibodies involved in the pathologic progress more directly than ELISA.…”

Molecular Mimicry in Campylobacter jejuni and Helicobacter pylori Lipopolysaccharides: Contribution of Gastrointestinal Infections to Autoimmunity

“…However, it is important to note that the situation in humans may be very different. Firstly, anti-GM 1 antibodies bind to the surface of peripheral nerve structures [60,61] Intraneural injection of rat sciatic nerve and muscle with anti-GM 1 antibodies and GBS sera have produced demyelination and acute conduction block in most studies [65][66][67][68][69][70][71][72][73], but this result could not be reproduced by others [74,75]. Furthermore, complement-mediated demyelination of rodent dorsal-root ganglion cell cultures was observed after passive transfer with human GBS sera [76,77].…”