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. 2025 Aug;32(8):e70310.
doi: 10.1111/ene.70310.

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

Alexandre Guérémy  1 , John Boudjarane  2 , Emilie Alazard  2 , Etienne Fortanier  1 , José Boucraut  3   4 , Norman Abbou  5 , Aude-Marie Grapperon  1 , Ludivine Kouton  1 , Annie Verschueren  1 , Emmanuelle Salort-Campana  1 , Shahram Attarian  1 , Emilien Delmont  1
Affiliations

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

Alexandre Guérémy et al. Eur J Neurol. 2025 Aug.

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 MYD88L256P mutation enhances its activity and promotes inflammatory pathways and autoimmune diseases. Our aim was to determine the frequency of the MYD88L256P 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 MYD88L256P 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 MYD88L256P 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 MYD88L256P mutation were more likely to have an IgM monoclonal gammopathy (13/27 vs. 8/87, p = 0.001). The MYD88L256P 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 MYD88L256P mutation is frequent in CIDP and MMN patients, suggesting new pathophysiological hypotheses and new therapeutic approaches.

Keywords: CIDP; MYD88; multifocal motor neuropathy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Frequency of MYD88L256P mutation. MYD88wt, wild type; CIDP, chronic inflammatory demyelinating polyradiculoneuropathies; MMN, multifocal motor neuropathies; Ctrl, nonimmune mediated disease controls.
FIGURE 2
FIGURE 2
Comparison of disease severity and IVIg efficacy according to MYD88 mutation for CIDP and MMN patients. CIDP, chronic inflammatory demyelinating polyradiculoneuropathy; IVIg, intravenous immunoglobulins; MMN, multifocal motor neuropathies; MYD88wt, wild type; NS, nonsignificant; ONLS, overall neuropathy limitation scale.
See this image and copyright information in PMC

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