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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Observational Study of the Prevalence of Some Genetic Mutations in Patients With Neuropathy Associated With Anti-Myelin-associated Glycoprotein (MAG) Antibodies.

Conditions
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Neuropathy Demyelinating

Intervention / Treatment
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* Diagnostic Test: Mutational analysis of clonal B cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with anti-MAG neuropathy Blood and/or bone marrow samples available in bio-bank Given informed consent Exclusion criterion Participation refusal

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with anti-MAG neuropathy<br>Mutational analysis of clonal B cells | Diagnostic Test: Mutational analysis of clonal B cells<br>* Mutational analysis based on medullary or blood samples stored in a bio-bank during routine lymphocyte phenotyping. Mutations affecting MYD88 (MYD88 L265P mutation), CXCR4 (Whim-like CXCR4 mutation) loci are sought.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunoglobulin gene rearrangement | Immunoglobulin gene rearrangements are determined with a multiplex PCR | At inclusion : after the patient's given consent | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anti-MAG neuropathy, Waldenström disease, Mutational analysis