title: Rituximab therapy for myopathy associated with anti-signal recognition particle antibodies: a case series.
abstract: OBJECTIVE
  The myopathy associated with anti-signal recognition particle (anti-SRP) is a severe necrotizing immune-mediated disease characterized by rapidly progressive proximal muscle weakness, markedly elevated serum creatine kinase (CK) levels, and poor responsiveness to traditional immunosuppressive therapies. Reports on the efficacy of B cell depletion therapy for anti-SRP-associated myopathy are mixed. We describe 8 patients with anti-SRP-associated myopathy and their response to treatment with the anti-CD20 monoclonal antibody rituximab.
  
  
  METHODS
  We identified 8 patients with myopathy who tested positive for anti-SRP antibodies by immunoprecipitation and were treated with rituximab as part of clinical care. We reviewed their medical records to assess clinical, serologic, and histologic characteristics and response to therapy. In 5 patients, serum was collected before and after rituximab therapy. Autoantibodies were detected by immunoprecipitation and quantitated by densitometry, and the percent decreases in anti-SRP autoantibody levels were calculated.
  
  
  RESULTS
  Six of 8 patients who had been refractory to standard immunosuppressive therapy demonstrated improved manual muscle strength and/or decline in CK levels as early as 2 months after rituximab treatment. Three patients sustained the response for 12-18 months after initial dosing. All of the patients were continued on adjunctive corticosteroids, but doses were substantially reduced after rituximab. Quantitative levels of serum anti-SRP antibodies also decreased after rituximab treatment.
  
  
  CONCLUSIONS
  B cell depletion therapy with rituximab is effective for patients with myopathy associated with anti-SRP. The substantial decrease in anti-SRP antibody levels after rituximab treatment also suggests that B cells and anti-SRP antibodies may play a role in the pathogenesis of this myopathy.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ritu
authors.initials: R
authors.lastname: Valiyil
authors.forename: Livia
authors.initials: L
authors.lastname: Casciola-Rosen
authors.forename: Grace
authors.initials: G
authors.lastname: Hong
authors.forename: Andrew
authors.initials: A
authors.lastname: Mammen
authors.forename: Lisa
authors.initials: L
authors.lastname: Christopher-Stine
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D009220:Myositis / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D012189:Retrospective Studies; D000069283:Rituximab; D018271:Signal Recognition Particle / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D018271:Signal Recognition Particle; D000069283:Rituximab; D003402:Creatine Kinase