Polyneuropathy associated with IgG/IgA monoclonal gammopathy: a clinical and electrophysiological study of 15 cases

Peripheral neuropathy has been widely reported in patients with monoclonal gammopathy (MG), more frequently immunoglobulin M (IgM) or IgG than IgA. Nevertheless, it remains unclear whether this association has clinical or pathogenic relevance. In order to clarify the possible role of IgG/IgA MG in neuropathy, we studied the clinical and electrophysiological features of 15 consecutive patients with polyneuropathy and IgG/IgA-MG, and compared them to those of 40 patients with polyneuropathy associated with IgM-MG, previously reported. Nine middle-aged patients (60%) had a chronic progressive or relapsing demyelinating polyneuropathy (DP) that was clinically and electrophysiologically indistinguishable from classic chronic inflammatory demyelinating polyneuropathy (CIDP) and frequently responded to immunosuppressive treatments, both characteristics supporting a dysimmune process. Six older patients (40%) had a chronic axonal distal polyneuropathy similar to the so-called chronic cryptogenic sensory polyneuropathy: there was no clear relationship with the MG in these patients and the response to immunosuppressive treatments was poor. Several features allowed us to distinguish between polyneuropathies associated with IgG/IgA-MG (IgG/IgA-PN) considered together and polyneuropathies associated with IgM-MG (IgM-PN). In the first group, the proportion of patients with a predominantly sensory clinical picture (27%) was less than that in the second group (75%), and there were fewer changes in nerve conduction studies. In addition, we found that the nine patients with DP associated with IgG/IgA-MG (IgG/IgA-DP) differed from the 31 with DP associated with IgM-MG (IgM-DP): clinical and electrophysiological studies clearly showed that the demyelinating pattern was more heterogeneous in IgG/IgA-DP than in IgM-DP. The spectrum of polyneuropathies associated with IgG/IgA-MG is heterogeneous, including DP, which is similar to classic CIDP, and axonal polyneuropathy, in which the pathogenic role of the MG remains elusive. In addition, IgG/IgA-DP differ from IgM-DP on clinical and electrophysiological grounds, suggesting probable different physiopathological mechanisms.