GENOMAG: Prevalence of Genetic Mutations in Patients With Neuropathy Associated With Anti-Myelin-associated Glycoprotein (MAG) Antibodies
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Patients with anti-MAG neuropathy Mutational analysis of clonal B cells |
Diagnostic Test: Mutational analysis of clonal B cells
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.
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Outcome Measures
Primary Outcome Measures
- 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
- Immunoglobulin gene rearrangement [At inclusion : after the patient's given consent]
Immunoglobulin gene rearrangements are determined with a multiplex PCR
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients with anti-MAG neuropathy
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Blood and/or bone marrow samples available in bio-bank
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Given informed consent
Exclusion criterion
- Participation refusal
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rennes University Hospital | Rennes | France | 35000 |
Sponsors and Collaborators
- Rennes University Hospital
Investigators
- Study Director: Olivier DECAUX, MD, PhD, CHU Rennes
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 35RC15_3018