Prevalence of Genetic Mutations in Patients With Neuropathy Associated With Anti-Myelin-associated Glycoprotein (MAG) Antibodies

Completed

• Conditions: Neuropathy Demyelinating
• Interventions: Diagnostic Test: Mutational analysis of clonal B cells

• Registration Number: NCT03268161
• Lead Sponsor: Rennes University Hospital

Brief Summary

Anti-MAG (Myelin Associated Glycoprotein) neuropathy is related to clonal B lymphocyte proliferation producing an monoclonal immunoglobulin (IgM) with anti-MAG activity. IgM may be a reflection of malignant lymphoproliferative syndrome (Waldenström disease) or, more often, monoclonal gammopathy of unknown significance.

The anti-MAG antibody has a direct toxicity on the myelin sheath of the peripheral nervous system responsible for a length-dependent demyelinating polyneuropathy. Clinically, this results in a sensitive, ataxic predominant polyneuropathy in the lower limbs, sometimes associated with a tremor of attitude and action tremor of the upper limbs.

Clonal B cells at the origin of IgM production may have acquired mutations affecting MYD88 (MYD88 L265P mutation) and CXCR4 (Whim-like CXCR4 mutation). The prevalence of the MYD88 L265P mutation is estimated to be 50% in monoclonal gammopathies of undetermined significance and more than 80% in Waldenström disease. CXCR4 Whim-like mutations are found in 40% of patients with Waldenström's disease.

No studies have reported the prevalence of these mutations in patients with anti-MAG neuropathies.

Detailed Description

This is a retrospective observational study in patients with anti-MAG neuropathy. Mutational analysis will be performed for patients with a medullary or blood sample stored in a bio-bank during lymphocyte phenotyping. This phenotyping was carried out most often in search of a malignant haemopathy associated with the monoclonal peak. No new samples were taken from the patient (blood or spinal cord).

Immunoglobulin gene rearrangement of the clonal B cells are also assessed.

Study Timeline

• Study Start: 2015-10-21
• Study First Submitted: 2017-08-29
• Study First Submitted QC: 2017-08-29
• Study First Posted: 2017-08-31
• Primary Completion: 2017-11-10
• Study Completion: 2017-11-10
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-26
• Last Update Posted: 2018-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• Patients with anti-MAG neuropathy
• Blood and/or bone marrow samples available in bio-bank
• Given informed consent

Exclusion criterion

• Participation refusal

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with anti-MAG neuropathy	Mutational analysis of clonal B cells	Mutational analysis of clonal B cells

Primary Outcome Measures

Name	Time	Method
Prevalence of MYD88 L265P mutations in anti-MAG neuropathies	At inclusion : after the patient's given consent	Mutational status of MYD88 L265P is assessed using high-throughput sequencing (HTS) and allele specific polymerase chain reaction (AS-PCR)
Prevalence of CXCR4 Whim-like mutations in anti-MAG neuropathies	At inclusion : after the patient's given consent	Mutational status of CXCR4 is assessed using HTS and AS-PCR

Secondary Outcome Measures

Name	Time	Method
Immunoglobulin gene rearrangement	At inclusion : after the patient's given consent	Immunoglobulin gene rearrangements are determined with a multiplex PCR

Trial Locations

Locations (1)

Rennes University Hospital; 🇫🇷 Rennes, France