[Immunoglobulins in hematology. Peripheral neuropathy associated with monoclonal IgM].
Peripheral neuropathy is often associated with a monoclonal IgM and occurs in about 3% of authentic Waldenström macroglobulinemias. In at least as many cases, the neuropathy is associated with a monoclonal IgM although lymphoplasmocyte proliferation is not detected, at least initially. In about 2/3 of the cases, the monoclonal IgM is a specific antibody against a myelin associated glycoprotein (MAG), two peripheral nerve glycolipids (SGPG and SGLPG), the peripheral nerve protein P0, other smaller molecular weight molecules of the peripheral nerves, or finally certain adhesion proteins such as N-CAM. All these IgM have a fine specificity against an epitope of the glucuronyl sulfate determinant present on the carbohydrate moiety of these proteins. The clinical manifestations are similar in all patients with sensorimotor polyneuropathy, with frequent sensory dominance and demyelinization. Atypical symptoms including motor dominance, paralysis of the cranial nerves, asymmetric forms, are rare. On histological examination, there is demyelinization and monoclonal IgM deposit along the nerve fibers. Passive in vivo and in vitro transfer experiences suggest that these monoclonal antibodies can play a role in triggering or maintaining the peripheral neuropathy. Despite identical or nearly identical antibody specificities of the monoclonal IgMs, the regions of the heavy or light chains involved vary from one patient to another, indicating that the glucoronyl sulfate determinant is quite variable. This variability is not found in other monoclonal autoantibody models with autoantibody activity such as the rheumatoid factor or cold agglutinins. These data would suggest the need for different therapeutic approaches using chemotherapy, plasmapheresis, high dose intravenous immunoglobulins and other immunomodulator treatments. Two therapeutic trials are discussed.
Brouet
J C
JC
Laboratoire d'Immunopathologie, Hôpital Saint-Louis, Paris.
D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000502:physiology; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D009154:Mutation; D009185:Myelin Proteins / Q000276:immunology; D010523:Peripheral Nervous System Diseases / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007075:Immunoglobulin M; D009185:Myelin Proteins
Immunoglobulines en Hématologie. Neuropathie périphérique associée à une IgM monoclonale.