Allenbach Yves, Drouot Laurent, Rigolet Aude, Charuel Jean Luc, Jouen Fabienne, Romero Norma B, Maisonobe Thierry, Dubourg Odile, Behin Anthony, Laforet Pascal, Stojkovic Tania, Eymard Bruno, Costedoat-Chalumeau Nathalie, Campana-Salort Emmanuelle, Tournadre Anne, Musset Lucile, Bader-Meunier Brigitte, Kone-Paut Isabelle, Sibilia Jean, Servais Laurent, Fain Olivier, Larroche Claire, Diot Elisabeth, Terrier Benjamin, De Paz Raphael, Dossier Antoine, Menard Dominique, Morati Chafika, Roux Marielle, Ferrer Xavier, Martinet Jeremie, Besnard Sophie, Bellance Remi, Cacoub Patrice, Arnaud Laurent, Grosbois Bernard, Herson Serge, Boyer Olivier, Benveniste Olivier
From the AP-HP, Hôpital Pitié-Salpêtrière, Department of Internal Medicine 1 and Inflammation-Immunopathology-Biotherapy Department (I2B), East Paris Neuromuscular Diseases Reference Center, Inserm U974, Université Pierre et Marie Curie, Paris 6, Paris (YA, AR, SH, O. Benveniste); Inserm, U905, Immunology Department, Normandie Univ, IRIB and Rouen University Hospital (LD, FJ, JM, O. Boyer); AP-HP, Hôpital Pitié-Salpêtrière, Department of Immunochemistry, Université Pierre et Marie Curie, Paris 6, Paris (JLC, LM); AP-HP, Hôpital Pitié-Salpêtrière, Institute of Myology, Unite de Morphologie Musculaire, CNRS-UMR7215, Paris (NBR); AP-HP, Hôpital Pitié-Salpêtrière, Department of Neuropathology, Université Pierre et Marie Curie, Paris 6, Paris (TM, OD); AP-HP, Hôpital Pitié-Salpêtrière, Department of Neurology, East Paris Neuromuscular Diseases Reference Center, Université Pierre et Marie Curie, Paris 6, Paris (AB, PL, TS, BE); AP-HP, Hôpital Cochin Centre de Référence Maladies Auto-Immunes et Systémiques Rares, Service de Médecine Interne Pôle Médecine, Université René Descartes Paris V, Paris (NCC, BT); APHM, Hôpital la Timone, Centre de Référence des Maladies Neuromusculaires, Marseille (ECS); Clermont-Ferrand University Hospital, Department of Rheumatology, Clermont-Ferrand (AT); AP-HP, Hôpital Necker, Department of Paediatric Rheumatology, Paris (BBM); AP-HP, Hôpital Bicêtre, Department of Paediatric Rheumatology, Kremlin-Bicêtre, Paris (IKP); CHU Strasbourg, Department of Rheumatology, Strasbourg (JS); Hôpital Pitié-Salpêtrière, Institute of Myology, Paris (LS); AP-HP, Hôpital Jean Verdier, Department of Internal Medicine, La Seine-Saint-Denis (OF); AP-HP, Hôpital Avicenne, Department of Internal Medicine, Bobigny (CL); CHRU Tours, Department of Internal Medicine, Tours (ED); Fondation A. de Rothschild, Department of Neurology, Paris (RDP); AP-HP, Hôpital Bichat, Department of Internal Medicine, Paris (AD); CHU Rennes, Department of Neurology, Rennes (DM); Centre Hospitalier de la Region d'Annecy, Department of Internal Medicine, Annecy (CM); Hôpital Pierre Oudot, Department of Internal Medicine, Bourgouin (MR); Hôpital du Haut Levêque, Department of Neurology, Bordeaux (XF); CHU Rennes, Department of Internal Medicine, Rennes (SB, BG); CHU Fort de France, Department of Neurology, Fort de France (RM); AP-HP, Hôpital Pitié-Salpêtrière, Departement Hospitalo-Universitaire I2B, UPMC Univ Paris 06, UMR 7211, INSERM, UMRS 959, Department of Internal Medicine 2, Paris (PC, LA); France.
Medicine (Baltimore). 2014 May;93(3):150-157. doi: 10.1097/MD.0000000000000028.
Necrotizing autoimmune myopathy (NAM) is a group of acquired myopathies characterized by prominent myofiber necrosis with little or no muscle inflammation. Recently, researchers identified autoantibodies (aAb) against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in patients with NAM, especially in statin-exposed patients. Here we report what is to our knowledge the first European cohort of patients with NAM.The serum of 206 patients with suspicion of NAM was tested for detection of anti-HMGCR aAb using an addressable laser bead immunoassay. Forty-five patients were found to be anti-HMGCR positive. Their mean age was 48.9 ± 21.9 years and the group was predominantly female (73.3%). Statin exposure was recorded in 44.4% of patients. Almost all patients had a muscular deficit (97.7%), frequently severe (Medical Research Council [MRC] 5 ≤3 in 75.5%). Subacute onset (<6 mo) was noted for most of them (64.4%). Nevertheless, 3 patients (6.6%) had a slowly progressive course over more than 10 years. Except for weight loss (20%), no extramuscular sign was observed. The mean CK level was high (6941 ± 8802 IU/L) and correlated with muscle strength evaluated by manual muscle testing (r = -0.37, p = 0.03). Similarly, anti-HMGCR aAb titers were correlated with muscular strength (r = -0.31; p = 0.03) and CK level (r = 0.45; p = 0.01). Mean duration of treatment was 34.1 ± 40.8 months, and by the end of the study no patient had been able to stop treatment.This study confirms the observation and description of anti-HMGCR aAb associated with NAM. The majority of patients were statin naive and needed prolonged treatments. Some patients had a dystrophic-like presentation. Anti-HMGR aAb titers correlated with CK levels and muscle strength, suggesting their pathogenic role.
坏死性自身免疫性肌病（NAM）是一组获得性肌病，其特征为明显的肌纤维坏死，肌肉炎症轻微或无炎症。最近，研究人员在NAM患者中，尤其是在使用他汀类药物的患者中，发现了针对3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）的自身抗体（aAb）。在此，我们报告据我们所知首个欧洲NAM患者队列。使用可寻址激光珠免疫测定法检测了206例疑似NAM患者的血清中的抗HMGCR aAb。发现45例患者抗HMGCR呈阳性。他们的平均年龄为48.9±21.9岁，该组以女性为主（73.3%）。44.4%的患者有他汀类药物使用史。几乎所有患者都有肌肉功能缺陷（97.7%），且通常较为严重（75.5%的患者医学研究委员会[MRC]评分≤3）。大多数患者起病亚急性（<6个月）（64.4%）。然而，3例患者（6.6%）病程超过10年，呈缓慢进展。除体重减轻（20%）外，未观察到肌肉外体征。平均肌酸激酶（CK）水平较高（6941±8802 IU/L），且与通过徒手肌力测试评估的肌肉力量相关（r = -0.37，p = 0.03）。同样，抗HMGCR aAb滴度与肌肉力量（r = -0.31；p = 0.03）和CK水平（r = 0.45；p = 0.01）相关。平均治疗持续时间为34.1±40.8个月，到研究结束时，没有患者能够停止治疗。本研究证实了与NAM相关的抗HMGCR aAb的观察和描述。大多数患者未使用过他汀类药物，需要长期治疗。一些患者有营养不良样表现。抗HMGR aAb滴度与CK水平和肌肉力量相关，提示其致病作用。
