Complement-mediated demyelination in patients with IgM monoclonal gammopathy and polyneuropathy

Article Abstract:

IgM monoclonal gammopathy, a disorder characterized by abnormal multiplication of white blood cells producing a single (monoclonal) antibody of the IgM class, is frequently associated with polyneuropathy, nerve damage affecting several nerves and leading to weakness, tremor, and loss of sensation. The IgM antibody (M protein) of some patients actually reacts with components of the myelin sheath, the material that covers nerves and insulates them, allowing normal electrical transmission. It is possible that the demyelination, or loss of myelin, associated with this condition is the result of attack by M proteins. The mechanisms by which this might happen were studied. One way antibodies can cause cell damage is by means of the complement (C) proteins, a group of proteins activated in a chain-reaction manner (cascade) by antibody-antigen complexes. The antibodies involved in these complexes are called complement-fixing antibodies, and when they bind to the antigen they recognize, the molecular unit so formed can activate the first complement molecule to begin the cascade. The molecule formed as the last step in the cascade is called the terminal-complement complex; it is capable of causing the death of the cell to which the antibody has bound by introducing pores in its membrane. This is clearly of use if the antigen is dangerous to the body, but dysfunctional if the antigen is a component of the body's own myelin. The IgM molecules of seven IgM monoclonal gammopathy patients were studied. Six were found to have IgMs that reacted with molecules known to be associated with myelin, while the seventh had an M protein that reacted with an unidentified myelin component. Other methods demonstrated that these M proteins were preferentially deposited on the majority of myelinated fibers of nerves, and that some of the nerve fibers also had complement molecules on their surfaces. The presence of complement proteins from both early (C1q) and late (C9 neoantigen) stages of the cascade suggests that the demyelination in these patients may, indeed, be the result of antibody deposition and mediated by complement. None of these compounds were found on nerves from seven normal subjects, seven patients with hereditary sensorimotor neuropathy, or seven patients with diabetic neuropathy. Additional details regarding the role of complement in the pathogenesis of this type of polyneuropathy are provided. (Consumer Summary produced by Reliance Medical Information, Inc.)

Research, Causes of, Demyelination, Demyelinating diseases, Immune complexes, Peripheral nerve diseases, Peripheral nervous system diseases, Complement (Immunology), Immunoglobulin M

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A 71-year-old man with progressive weakness and a gammopathy

Article Abstract:

A 71-year-old man was diagnosed with muscle disease and a condition called Waldenstrom's macroglobulinemia. This condition is caused by excessive amounts of the antibody IgM in blood. Because the normal production of other antibodies is decreased, patients develop chronic infections. This man was admitted to a hospital with chronic and progressive muscle weakness, difficulty swallowing and a history of lung and sinus infections. Diagnostic tests and bone marrow biopsies revealed Waldenstrom's macroglobulinemia and a muscle disease called motor neuron disease.

Diagnosis, Muscle diseases, Muscular diseases, Macroglobulinemia, Waldenstrom macroglobulinemia

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Monoclonal gammopathy of undetermined significance

Article Abstract:

A 58-year-old man with no significant medical history was found to have an elevated total protein concentration (8.1 g per deciliter) on a routine blood chemical study, although he was asymptomatic and his physical examination was normal. A discussion on the management of the condition includes suggestions on further evaluation and how the patient should be followed, assuming the diagnosis of monoclonal gammopathy of undetermined significance is made.

Case studies, Monoclonal gammopathies, Case study

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