title: Clinical Features and Diagnostic Usefulness of Antibodies to Clustered Acetylcholine Receptors in the Diagnosis of Seronegative Myasthenia Gravis.
abstract: OBJECTIVE
  Cell-based assays (CBAs) were shown to improve detection of acetylcholine receptor (AChR) antibodies in patients with myasthenia gravis (MG). Herein, we asked whether these assays were able to help determine the diagnosis in patients studied in routine clinical practice.
  
  
  OBJECTIVE
  To determine the diagnostic usefulness of CBAs in the diagnosis of MG and to compare the clinical features of patients with antibodies only to clustered AChRs with those of patients with seronegative MG (SNMG).
  
  
  METHODS
  All patients with clinical suspicion of MG who were seen within the Division of Clinical Neurology at the John Radcliffe Hospital in Oxford, England, between November 1, 2009, and November 30, 2013. Their serum antibodies and clinical features were studied.
  
  
  METHODS
  Radioimmunoprecipitation assay (RIPA) and CBA were used to test for standard AChR antibodies and antibodies to clustered AChRs in 138 patients. All available samples from patients with SNMG were retrospectively tested for lipoprotein receptor-related protein 4 (LRP4) antibodies.
  
  
  METHODS
  Demographic, clinical, neurophysiological, and laboratory data.
  
  
  RESULTS
  In total, 138 patients were tested for antibodies to clustered AChRs, and 42 had a final diagnosis of MG. The clustered AChR CBA detected antibodies in 38.1% (16 of 42) of RIPA-negative patients with MG with 100% specificity. All patients with SNMG who were tested for LRP4 antibodies (21 of 26) were negative by CBA. Compared with patients with SNMG, patients with antibodies only to clustered AChRs had frequent prepubertal onset (62.5% [median age, 6 years; age range, 1-52 years] vs 11.5% [median age, 38 years; age range, 2-72 years], P ≤ .05), high prevalence of ocular MG (62.5% vs 42.3%), milder disease severity with less bulbar involvement (25.0% vs 46.2%), and absence of respiratory symptoms (0% vs 23.1%). Response to treatment and prognosis was good, with a reduced need for thymectomy (6.3% vs 19.2%) and a high proportion of patients going into remission (50.0% vs 8.3%, P ≤ .05). These observations also apply to the classic AChR MG phenotype seen in large series.
  
  
  CONCLUSIONS
  Cell-based assay is a useful procedure in the routine diagnosis of RIPA-negative MG, particularly in children. Patients with antibodies only to clustered AChRs appear to be younger and have milder disease than other patients with MG. These observations will have implications in planning treatment.
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England2Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Rodríguez Cruz
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Michal
authors.initials: M
authors.lastname: Al-Hajjar
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Saif
authors.initials: S
authors.lastname: Huda
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Leslie
authors.initials: L
authors.lastname: Jacobson
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodhall
authors.affiliation: Department of Paediatric Neurology, Children's Hospital, John Radcliffe Hospital, Oxford, England.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Jayawant
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Camilla
authors.initials: C
authors.lastname: Buckley
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: David
authors.initials: D
authors.lastname: Hilton-Jones
authors.affiliation: Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: David
authors.initials: D
authors.lastname: Beeson
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Leite
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Palace
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies; D001681:Biological Assay / Q000592:standards; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000175:diagnosis* / Q000276:immunology / Q000503:physiopathology; D010641:Phenotype; D011950:Receptors, Cholinergic / Q000276:immunology*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D011950:Receptors, Cholinergic