title: Clinical features and prognosis in anti-SRP and anti-HMGCR necrotising myopathy.
abstract: To elucidate the common and distinct clinical features of immune-mediated necrotising myopathy (IMNM), also known as necrotising autoimmune myopathy associated with autoantibodies against signal recognition particle (SRP) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR).
  
  
  
  We examined a cohort of 460 patients with idiopathic inflammatory myopathies (IIMs) through a muscle biopsy-oriented registration study in Japan. Study entry was strictly determined by the comprehensive histological assessment to exclude other neuromuscular disorders. Anti-SRP and anti-HMGCR antibodies were detected by RNA immunoprecipitation and ELISA, respectively.
  
  
  
  Of 460 patients with IIM, we diagnosed 73 (16%) as having inclusion body myositis (IBM). Of 387 patients with IIMs other than IBM, the frequencies of anti-SRP and anti-HMGCR antibodies were 18% and 12%, respectively. One patient had both autoantibodies. Severe limb muscle weakness, neck weakness, dysphagia, respiratory insufficiency and muscle atrophy were more frequently observed in patients with anti-SRP antibodies than in those with anti-HMGCR antibodies. Serum creatine levels were markedly higher in the patients with autoantibodies than in those without. Histology was characterised by necrosis and regeneration of muscle fibres and was consistent with IMNM except in 1 HMGCR-positive IBM patient. Most patients were initially treated with corticosteroids; however, additional immunosuppressive drugs were required, especially in the patients with anti-SRP antibodies. Rates of unsatisfactory neurological outcome were similar in the 2 autoantibody groups.
  
  
  
  Anti-SRP antibodies are associated with severe neurological symptoms, more so than are anti-HMGCR antibodies. Although these autoantibodies are independent serological markers associated with IMNM, patients bearing either share common characteristics.
authors.affiliation: Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yurika
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, Tokyo, Japan Department of Genome Medicine Development, Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Uruha
authors.affiliation: Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Jin
authors.initials: J
authors.lastname: Nakahara
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, Tokyo, Japan Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Hamanaka
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, Tokyo, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, Tokyo, Japan.
authors.forename: Ichizo
authors.identifier: 0000-0001-9452-112X
authors.initials: I
authors.lastname: Nishino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003346:Corticotropin-Releasing Hormone / Q000276:immunology*; D003402:Creatine Kinase / Q000097:blood; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000276:immunology*; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009220:Myositis / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D018979:Myositis, Inclusion Body / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009336:Necrosis; D009460:Neurologic Examination; D012744:Sex Ratio; D054832:Urocortins / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; C426705:UCN2 protein, human; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases; D003402:Creatine Kinase