Multifocal motor neuropathy caused by a B‐cell lymphoma producing a monoclonal IgM autoantibody against peripheral nerve myelin glycolipids GM1 and GD1b

Abstract

Summary. Various data support the pathogenetic significance of serum IgM autoantibodies against glycolipid GM1 in patients with multifocal motor neuropathy. Although some patients with this neuropathy have an extraneural lymphoma, IgM anti-GM1 glycolipid autoantibodies have not been investigated in these cases. We found IgM anti-GM1 autoantibody in the serum of a 52-year-old man who developed multifocal motor neuropathy that was associated with an extraneural diffuse large B-cell lymphoma. An autopsy showed severe widespread demyelination without lymphoma cell infiltration in the peripheral nerves. Immunofluorescent flow cytometry and thin-layer chromatographic immunostaining demonstrated that most of the anti-GM1 antibody in the serum was monoclonal IgM of k type, which was also demonstrable in secretory form on lymphoma cells. The antibody showed affinity for the Galb1-3GalNAc terminal disaccharide of glycolipids GM1 and GD1b, which both are widespread in peripheral nerve myelin. Enzyme-linked immunosorbent assay demonstrated that this antibody was much more abundant in lymphoma cell culture supernatant than in normal lymphocyte culture supernatant. Thus, our patient's B-cell lymphoma cells produced a monoclonal IgM k autoantibody against this terminal disaccharide residue. This antibody bound to glycolipids GM1 and GD1b in peripheral motor nerve myelin, presumably initiating formation of destructive immune complexes that caused multifocal motor neuropathy.

Lymphoma and peripheral neuropathy: A clinical review

“…74,140 In some cases, antibodies likely derived from molecular mimicry of antigens in lymphoma cells or accompanying viral infections may attack similar antigens in nerve cells. 2 Examples include anti-Hu neuropathy, 20,21,85 multifocal motor neuropathy, 96 neuromyotonia, 78 and perhaps GBS and CIDP.…”

“…68,99 Lymphoma cells can affect peripheral nerves remotely, causing generalized neuropathies. 57,58,96,132 Examples include NHL, chronic lymphocytic leukemia, Waldenström's macroglobulinemia, and osteosclerotic myeloma. 67 These may be due to circulating anti-nerve monoclonal antibodies secreted by the tumor cells or other factors as yet unknown, as in the case of osteosclerotic myeloma.…”

“…In some cases, the monoclonal anti-nerve antibodies, usually immunoglobulin-M paraproteins, are directed at specific antigens such as myelin-associated glycoprotein and the ganglioside GM1. 57,58,66,76,96 Nonmalignant lymphopoliferative disorders, such as Castleman's disease (angiofollicular lymph node hyperplasia), may cause neuropathy, 26,140 sometimes associated with Crow-Fukase syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes; POEMS syndrome). 66,91 Although not a focus of this review, they often feature in the differential diagnosis of lymphomatous neuropathies.…”

Immune-mediated Neuropathy with Anti-disialosyl IgM Antibodies in Diffuse Large B-cell Lymphoma: A Case Report and Literature Review

“…Some reports have supported the possible correlation between GBS and cancer (14,15), and it is hypothesized that the pathophysiology is due to antibodies derived from the molecular mimicry of antigens in lymphoma cells which may attack similar antigens in the peripheral nerve cells (1). Among the patients which were listed in Table, Noguchi et al demonstrated that their patient's B cell lymphoma produced a monoclonal IgM autoantibody against glycolipids GM1 and GD1b, which caused multifocal motor neuropathy (5). Therefore, we speculated that anti-disialosyl IgM antibodies may be medi-ated by lymphoma in the present case.…”

Update on Paraneoplastic Neurologic Disorders

“…Vibration and pin sensation are most affected. In some patients, the neuropathy is a result of the deposition of serum IgM in peripheral nerves, sometimes with antibody activity against myelinassociated glycoprotein and gangliosides [87,88]. The neuropathy may respond to treatment directed at Waldenström's macroglobulinemia.…”