Clinical trial NCT03268161: Prevalence of Genetic Mutations in Patients With Neuropathy Associated With Anti-Myelin-associated Glycoprotein (MAG) Antibodies
Official title: Observational Study of the Prevalence of Some Genetic Mutations in Patients With Neuropathy Associated With Anti-Myelin-associated Glycoprotein (MAG) Antibodies.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neuropathy Demyelinating
Keywords: anti-MAG neuropathy
Waldenström disease
Mutational analysis
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2017-08-31
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with anti-MAG neuropathy followed in the Internal Medicine Ward of the Rennes University Hospital

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion criterion

* Participation refusal

Primary outcomes:
measure: Prevalence of MYD88 L265P mutations in anti-MAG neuropathies
timeFrame: At inclusion : after the patient's given consent
measure: Prevalence of CXCR4 Whim-like mutations in anti-MAG neuropathies
timeFrame: At inclusion : after the patient's given consent
Secondary outcomes:
measure: Immunoglobulin gene rearrangement
timeFrame: At inclusion : after the patient's given consent
Other outcomes:
Locations:
city: Rennes
country: France
facility: Rennes University Hospital
Study officials:
affiliation: CHU Rennes
name: Olivier DECAUX, MD, PhD
role: STUDY_DIRECTOR
References: