Peripheral neuropathy and paraproteinemia: an immunohistochemical and serologic study

Four of 132 consequtive patients with paraproteinemia and with an M-component presented exclusively with neurological symptoms. A sural nerve biopsy was performed in all patients. In one case direct immunofluorescence revealed deposition of immunoglobulin corresponding to the M-component along the perineurium. No deposition of immunoglobulin was found along the myelin sheaths and the patient's serum revealed no immunoreactivity towards normal peripheral myelin or other components of normal peripheral nerves. In a second case, deposition of immunoglobulin corresponding to the M-component was found along the myelin sheaths, and this patient's paraprotein showed immunoreactivity towards normal peripheral myelin. Two patients showed no in situ bound immunoglobulin in the nerve biopsies and their sera did not react with any component in normal peripheral nerves. The patient with deposition of immunoglobulin along the perineurium had severe demyelination and severe peripheral sensory-motor neuropathy, while the patient with immunoglobulin deposition along the myelin sheaths had a slight sensory neuropathy which had not progressed for 4 years. Based on these findings the pathogenesis of neuropathy in patients with paraproteinemia is discussed, and it is concluded that although there is evidence for immune-mediated neuropathy in the patients, the histologic, immunohistochemical and clinical data are conflicting and the exact pathogenic pathway is still unknown.