Absence of Pathogenic Mutations and Strong Association With HLA-DRB1∗11:01 in Statin-Naïve Early-Onset Anti-HMGCR Necrotizing Myopathy
Llansó, Laura (Institut de Recerca Sant Pau)
Segarra Casas, Alba (Institut de Recerca Sant Pau)
Domínguez-González, Cristina (Instituto de Salud Carlos III)
Malfatti, Edoardo (Universidad del País Vasco)
Kapetanovic, S. (Hôpital Mondor)
Rodríguez-Santiago, Benjamín (Institut de Recerca Sant Pau)
Calle Martín, Óscar de la (Institut de Recerca Sant Pau)
Blanco, Ricardo (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Dobrescu, A. (Craiova University Hospital)
Nascimento-Osorio, A. (Hospital Sant Joan de Déu (Esplugues de Llobregat, Catalunya))
Paipa, Andrés (Hospital Universitari de Bellvitge)
Hernandez-Lain, A. (Hospital 12 de Octubre (Madrid))
Jou, C. (Hospital Sant Joan de Déu (Esplugues de Llobregat, Catalunya))
Mariscal, Anaís (Institut de Recerca Sant Pau)
González-Mera, L. (Hospital de Viladecans)
Arteche, A. (Hospital 12 de Octubre (Madrid))
Lleixà, Cinta (Institut de Recerca Sant Pau)
Caballero-Ávila, Marta (Neuromuscular Diseases Unit)
Carbayo Viejo, Álvaro (Institut de Recerca Sant Pau)
Vesperinas-Castro, Ana (Neuromuscular Diseases Unit)
Querol, Luis (Institut de Recerca Sant Pau)
Gallardo, Eduard (Institut de Recerca Sant Pau)
Olivé i Plana, Montserrat (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	Background and Objectives Immune-mediated necrotizing myopathy (IMNM) caused by antibodies against 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is an inflammatory myopathy that has been epidemiologically correlated with previous statin exposure. We characterized in detail a series of 11 young statin-naïve patients experiencing a chronic disease course mimicking a limb-girdle muscular dystrophy. With the hypothesis that HMGCR upregulation may increase immunogenicity and trigger the production of autoantibodies, our aim was to expand pathophysiologic knowledge of this distinct phenotype. MethodsClinical and epidemiologic data, autoantibody titers, creatine kinase (CK) levels, response to treatment, muscle imaging, and muscle biopsies were assessed. HMGCR expression in patients' muscle was assessed by incubating sections of affected patients with purified anti-HMGCR+ serum. Whole-exome sequencing (WES) with a special focus on cholesterol biosynthesis-related genes and high-resolution human leukocyte antigen (HLA) typing were performed. Results Patients, aged 3-25 years and mostly female (90. 9%), presented with subacute proximal weakness progressing over many years and high CK levels (.
Grants:	Instituto de Salud Carlos III PI21/01621
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Neurology® neuroimmunology & neuroinflammation, Vol. 11 Núm. 5 (june 2024) , p. e200285, ISSN 2332-7812

DOI: 10.1212/NXI.0000000000200285
PMID: 39106428

12 p, 1.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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