Clinical, biological, electrophysiological and therapeutic profile of patients with anti-MAG neuropathy according to MYD88 L265P and CXCR4 mutations and underlying haemopathy.

Autor: Guérémy A; Referral Centre for Neuromuscular Diseases and ALS, Hospital La Timone, 264 Rue Saint Pierre, 13005, Marseille, France., Boucraut J; APHM, Hôpital de La Timone, Service d'Immunologie, Marseille-Immunopole, Marseille, France.; AMU, Institut de Neurosciences des Systèmes (INS, UMR1106), Marseille, France., Boudjarane J; Laboratory of Constitutional Cytogenetics, Department of Medical Genetics, La Timone Hospital Marseille, Marseille, France., Grapperon AM; Referral Centre for Neuromuscular Diseases and ALS, Hospital La Timone, 264 Rue Saint Pierre, 13005, Marseille, France., Fortanier E; Referral Centre for Neuromuscular Diseases and ALS, Hospital La Timone, 264 Rue Saint Pierre, 13005, Marseille, France., Farnault L; Haematology and Cellular Therapy Department, La Conception, University Hospital of Marseille, Marseille, France.; APHM Head of Biochemistry and Molecular Biology, Hopital Nord chemin des Bourrely, 13015, Marseille, France., Gabert J; INT Bd Jean Moulin Aix-Marseille University UMR7289, Marseille, France.; Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France., Vely F; APHM, Hôpital de La Timone, Service d'Immunologie, Marseille-Immunopole, Marseille, France.; Aix-Marseille University, CNRS, INSERM, CIML, Marseille, France., Lacroix R; Center for CardioVascular and Nutrition Research (C2VN), Faculty of Medical and Paramedical Sciences, Aix-Marseille University, National Institute of Health and Medical Research (INSERM), National Research Institute for Agriculture, Food and Environment (INRAE), 13005, Marseille, France.; Laboratoire d'Hématologie et de Biologie Vasculaire, Assistance Publique-Hôpitaux de Marseille, Marseille, France., Kouton L; Referral Centre for Neuromuscular Diseases and ALS, Hospital La Timone, 264 Rue Saint Pierre, 13005, Marseille, France., Attarian S; Referral Centre for Neuromuscular Diseases and ALS, Hospital La Timone, 264 Rue Saint Pierre, 13005, Marseille, France., Delmont E; Referral Centre for Neuromuscular Diseases and ALS, Hospital La Timone, 264 Rue Saint Pierre, 13005, Marseille, France. emilien.delmont@ap-hm.fr.
Jazyk: angličtina
Zdroj: Journal of neurology [J Neurol] 2024 Mar; Vol. 271 (3), pp. 1320-1330. Date of Electronic Publication: 2023 Nov 18.
DOI: 10.1007/s00415-023-12068-4
Abstrakt: Introduction: Anti-MAG neuropathies are associated with an IgM monoclonal gammopathy of undetermined significance (MGUS) or with a malignant haemopathy. Our objective was to determine whether the presence of a haemopathy or somatic mutations of MYD88 and CXCR4 genes influences disease presentation and response to rituximab (RTX).
Methods: We included 79 patients (mean age 74 years, disease duration 9.68 years) who had a bone marrow aspiration with morphologic and immunophenotypic analysis. MYD88 L265P and CXCR4 mutations were analysed in peripheral B cells. Information collected included: inflammatory neuropathy cause and treatment sensory sum score (ISS), MRC testing, overall neuropathy limitation scale (ONLS), Rash-built Overall Disability Score (RODS), ataxia score, anti-MAG titres, peak IgM dosage, neurofilament light chain levels, motor and sensory amplitudes, motor unit index (MUNIX) and motor unit size index (MUSIX) sum scores. Efficacy of RTX was evaluated at 12 months in 26 patients.
Results: Malignant haematological disorders were discovered in 17 patients (22%): 13 Waldenstrom macroglobulinemia, 3 marginal zone lymphoma and one mantle cell lymphoma. MYD88 L265P mutation was detected in 29/60 (48%) patients and CXCR4 in 1 single patient. Disease severity, biological and electrophysiological data and response to RTX were comparable in patients with MGUS/lymphoma and patients with/without MYD88 L265P mutation. ISS was lower and MUSIX higher in patients improved by RTX.
Conclusions: MYD88 L265P mutation and underlying haemopathies are not predictive of a more severe disease. However, in cases of resistant and progressive neuropathy, they provide an opportunity to prescribe newly available drugs such as Bruton tyrosine kinase inhibitors.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
Databáze: MEDLINE
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