Frequency and Relevance of MYD88L256P Mutation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy

Abstract

Background

The myeloid differentiation primary response 88 (MYD88) protein is involved in immune processes through the activation of the toll-like receptors and the interleukin-1 receptor. The acquired MYD88^L256P mutation enhances its activity and promotes inflammatory pathways and autoimmune diseases. Our aim was to determine the frequency of the MYD88^L256P mutation in chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) and multifocal motor neuropathy with conduction blocks (MMN) and to assess its potential effect on the phenotype of the neuropathy.

Methods

The MYD88^L256P mutation was tested in the peripheral blood mononuclear cells of 79 CIDP, 35 MMN, and 57 controls with nonimmune mediated disorders. Disease severity was assessed on disability scores, neurofilament light chain dosages, motor unit counts, and sums of the sensory and motor amplitudes on electrodiagnostic tests.

Results

The MYD88^L256P mutation was more frequent in MMN patients (12/35, 34%; odds ratio 28 [95% confidence interval 4–1262]; p < 0.001) and in CIDP patients (15/79, 19%; OR 13 [95% confidence interval 2–561]; p < 0.001) than in controls (1/57, 2%). Patients with the MYD88^L256P mutation were more likely to have an IgM monoclonal gammopathy (13/27 vs. 8/87, p = 0.001). The MYD88^L256P mutation remains more frequent in CIDP and MMN patients, even if patients with IgM monoclonal gammopathy were excluded. All the other characteristics were similar, especially the severity of the disease and the efficacy of intravenous immunoglobulins.

Conclusions

The MYD88^L256P mutation is frequent in CIDP and MMN patients, suggesting new pathophysiological hypotheses and new therapeutic approaches.