Observational Study of the Prevalence of Some Genetic Mutations in Patients With Neuropathy Associated With Anti-Myelin-associated Glycoprotein (MAG) Antibodies.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Prevalence of MYD88 L265P mutations in anti-MAG neuropathies
Study Overview
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 Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Retrospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Outcomes
Primary Outcomes
Prevalence of MYD88 L265P mutations in anti-MAG neuropathies
Time Frame: 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
Time Frame: At inclusion : after the patient's given consent
Mutational status of CXCR4 is assessed using HTS and AS-PCR
Secondary Outcomes
- Immunoglobulin gene rearrangement(At inclusion : after the patient's given consent)