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

NCT03268161 | Completed

• 1 other identifier: 35RC15_3018
• Study Type: observational
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuropathy Demyelinating

Keywords

anti-MAG neuropathy; Waldenström disease; Mutational analysis

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Immunoglobulin gene rearrangement

  At inclusion : after the patient's given consent

Study Arms (1)

Patients with anti-MAG neuropathy

Mutational analysis of clonal B cells

Diagnostic Test: Mutational analysis of clonal B cells

Interventions

Mutational analysis of clonal B cells DIAGNOSTIC_TEST

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.

Patients with anti-MAG neuropathy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with anti-MAG neuropathy followed in the Internal Medicine Ward of the Rennes University Hospital

You may qualify if:

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

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (1)

Rennes University Hospital

Rennes, 35000, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Medullary or blood sample stored in a bio-bank during lymphocyte phenotyping

Study Officials

• Olivier DECAUX, MD, PhD

  CHU Rennes

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2017
• First Posted: August 31, 2017
• Study Start: October 21, 2015
• Primary Completion: November 10, 2017
• Study Completion: November 10, 2017
• Last Updated: February 27, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)