Myeloma Neuropathy: Passive Transfer from Man to Mouse

Abstract

Mice were injected daily, for up to 10 weeks, with purified monoclonal immunoglobulin G from patients with myelomatous polyneuropathy or benign gammopathy. The animals developed a demyelinating polyneuropathy with slowed nerve conduction velocities. The putative antinerve factor may be an antibody since injection of Fab fragments from the monoclonal immunoglobulin G produced a similar demyelination. This provides evidence of a circulating factor in the serum of myeloma patients with polyneuropathy that reproduces typical features of the human disease on passive transfer. This disorder is thus distinguished from other neuropathies that occur as remote effects of malignant disease but have no identified pathogenic factors associated with them.

A Complement-Dependent Model of Thrombotic Thrombocytopenic Purpura Induced by Antibodies Reactive with Endothelial Cells

“…Monoclonal antibodies raised against a variety of cells and tissues are useful reagents for studying different models of immunologic injury (17)(18)(19). In this paper, we exploit one endothelial reactive monoclonal antibody to produce a complement-dependent model in rats with features of TTP.…”

Poems syndrome. Study of a patient with proteinuria, microangiopathic glomerulopathy, and renal enlargement

“…The role of monoclonal protein in the development of neuropathy is supported by a number of experimental studies (24,25). Experimental demyelinating neuropathy has been induced in mice by subcutaneous transplantation of light chain-secreting plasma cell tumors (24) We believe this is the first report of renal enlargement and glomerular microangiopathy in a patient with POEMS syndrome.…”

Monoclonal antibodies to myelin-associated glycoprotein reveal antigenic structures and suggest pathogenic mechanisms

“…This separation of the myelin lamellae probably results from the accumulation of immunoglobulin and while it has been observed in other conditions, such as experimental allergic neuritis [24], it is assumed to reflect antibody-mediated damage; third, purified monoclonal antibodies isolated from the sera of patients with polyneuropathy and myeloma have been reported to induce demyelination in mice [4] ; and fourth, monoclonal IgM from patients with neuropathy has been shown to bind to myelin of both the peripheral and central nervous system [12] The delineation of an immune-mediated disease, however, requires that a specific antigen should be identified as the target for the monoclonal immunoglobulins. In the case of demyelinating neuropathy it is imperative to demonstrate specific binding of the immunoglobulin to a surface antigen of myelin or Schwann cells.…”