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Peripheral neuropathy in macroglobulinemia: incidence and antigen-specificity of M proteins
Abstract:
Peripheral neuropathy was found in 12 (46%) of 26 patients with macroglobulinemia. The neuropathy was subclinical in two. Anti-myelin-associated glycoprotein (MAG) activity was found in six (50%) patients with neuropathy. Sural nerve biopsies showed demyelination and IgM deposits on the myelin sheath. In one patient who had no anti-MAG activity, the serum IgM bound to peripheral myelin by indirect immunofluorescence and to several protein bands in peripheral nerve and other tissues by immunoblot. In the other five patients with neuropathy, we found no binding of M proteins to nerve components, but in three patients there were endoneurial IgM deposits in nerve biopsy. Peripheral neuropathy may be related to the antigen-specificity of M proteins.
Insights
Peripheral neuropathy affects nearly half of macroglobulinemia patients, sometimes without symptoms. This study explores the link between M proteins, anti-myelin-associated glycoprotein (MAG) activity, and nerve damage in these patients.
Area of Science:
- Neurology
- Immunology
- Hematology
Background:
- Macroglobulinemia is a rare B-cell cancer.
- Peripheral neuropathy is a known complication of macroglobulinemia.
Purpose of the Study:
- To investigate the prevalence and characteristics of peripheral neuropathy in macroglobulinemia patients.
- To explore the role of anti-myelin-associated glycoprotein (MAG) activity and M protein binding in the pathogenesis of neuropathy.
Main Methods:
- Patient cohort assessment (n=26) for peripheral neuropathy.
- Measurement of anti-MAG antibody activity.
- Sural nerve biopsies for histopathology and immunofluorescence.
- Immunoblotting and immunofluorescence assays for M protein binding to nerve components.
Main Results:
- Peripheral neuropathy observed in 46% of patients, with 2 cases being subclinical.
- Anti-MAG activity detected in 50% of neuropathic patients.
- Nerve biopsies revealed demyelination and IgM deposits; M protein binding to myelin was confirmed in one patient without anti-MAG activity.
Conclusions:
- Peripheral neuropathy is common in macroglobulinemia.
- The pathogenesis may involve anti-MAG antibodies or direct M protein binding to peripheral nerve antigens.
- Antigen-specificity of M proteins may be crucial in developing neuropathy.