Monoclonal IgM with unique specificity to gangliosides GM ₁ and GD _1b and to lacto‐ N ‐tetraose associated with human motor neuron disease

Abstract

IgM lambda monoclonal antibodies in two patients with motor neuron disease showed the same unique antigenic specificity. They bound to gangliosides GM1 and GD1b and to lacto-N-tetraose-BSA. By immunofluorescence microscopy they bound to central and peripheral nerve tissue and to motor end-plates at the neuromuscular junction. Sera from control subjects did not contain antibodies of similar specificity. Monoclonal IgMs with the same unique specificity could be responsible for motor neuron disease in some patients with monoclonal gammopathies.

Autoantibody pathogenicity in a multifocal motor neuropathy induced pluripotent stem cell–derived model

“…[5][6][7][8][9] However, their pathogenicity to nerves remains to be established. Because CB and anti-GM1 specificity of IgG autoantibodies are also characteristics of acute motor axonal neuropathy, a pathogenic model of MMN in which anti-GM1 IgM antibodies cause complement-mediated structural changes at the nodes of Ranvier has been proposed.…”

Immunosuppressive Treatment in Lower Motor Neuron Syndrome with Autoantibodies against GM1 Ganglioside

“…Some other reports also emphasized the improvement after treatment with chlor ambucil or prednisone [6,7]. However, in these cases, as it is hard to have control patients for comparison, one cannot rule out the possibility of spontaneous remission of MND [16], As IgM to GM 1 ganglioside antibodies of varying specifities may be present nonspecifically at low titers in many patients with and without MND as well as in nor mal controls, focusing treatment on lowering anti-GM 1 antibodies is controversial.…”

“…Pestronk et al [2,3] found a high titer of GM 1 ganglioside antibodies in MND with predominantly lower motor neuron (LMN) signs and motor neuropathy [4,5]. In some cases with LMN disorders and multifocal motor neuropathy with conduction block, improvement in strength has occurred after a reduction in anti-GM 1 antibody titer by treatment with immunosuppressive medication [6,7], There have also been reports of some cases of a LMN form of MND, with high titer anti-GM 1 antibodies but without conduction block and M protein, who improved after immunosuppressive treatment [8].…”

Multifocal Motor Neuropathy: Update on Clinical Characteristics, Pathophysiological Concepts and Therapeutic Options

“…Similar to CB, anti-GM1 antibodies are not specific for MMN. They also occur in 5–10% of patients with MND, other immune-mediated neuropathies (GBS, CIDP) and even in healthy individuals [102,103,104,105], although GM1 titers are usually lower under these conditions compared to MMN [22,106]. Interestingly, anti-GM1-antibodies of the IgG subclass are frequently found at high concentrations in patients with MADSAM neuropathy [107], GBS and MND [99].…”