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

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

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.

Study Overview

• Status: Completed
• Conditions: Neuropathy Demyelinating
• Intervention / Treatment: Diagnostic test: Mutational analysis of clonal B cells

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 Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35000
    • Rennes University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

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

Exclusion criterion

• Participation refusal

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Study Director: Olivier DECAUX, MD, PhD, CHU Rennes

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 21, 2015
• Primary Completion (ACTUAL): November 10, 2017
• Study Completion (ACTUAL): November 10, 2017

Study Registration Dates

• First Submitted: August 29, 2017
• First Submitted That Met QC Criteria: August 29, 2017
• First Posted (ACTUAL): August 31, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 27, 2018
• Last Update Submitted That Met QC Criteria: February 26, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: anti-MAG neuropathy; Waldenström disease; Mutational analysis
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: 35RC15_3018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No