title: Characterization of anti-natalizumab antibodies in multiple sclerosis patients.
abstract: BACKGROUND
  A small proportion of multiple sclerosis (MS) patients treated with natalizumab develop anti-drug antibodies.
  
  
  OBJECTIVE
  The objective of this paper is to characterize the anti-natalizumab antibody response and to investigate differences between persistently and transiently antibody-positive patients.
  
  
  METHODS
  Screening for anti-natalizumab antibodies was performed using a standardized bridging ELISA. Antibody-positive samples were further analyzed for IgM and IgG1-4 antibodies using ELISA and ImmunoCAP®.
  
  
  RESULTS
  Anti-natalizumab antibodies developed in 57 of 1379 (4.1%) treated patients after a median treatment duration of three months. Of the positive patients, 20 (35%) patients reverted to negative, 19 (33%) patients were confirmed persistently positive and 18 (32%) patients were unconfirmed positive. Significantly higher anti-natalizumab antibody levels were detected in persistently compared to transiently positive patients. A cutoff value predicting persistence of antibodies could be determined with a sensitivity of 0.84 and a specificity of 0.80. IgM and IgG4 antibody levels were significantly higher in persistently compared to transiently positive patients, and IgG1, IgG2 and IgG4 increased significantly over time.
  
  
  CONCLUSIONS
  The level of total anti-natalizumab antibodies in a first positive sample can be used to predict patients at risk for persisting antibody positivity. However, neither IgM nor IgG1-4 antibodies could be used to discriminate between transiently and persistently positive patients.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Lundkvist
authors.forename: E
authors.initials: E
authors.lastname: Engdahl
authors.forename: C
authors.initials: C
authors.lastname: Holmén
authors.forename: R
authors.initials: R
authors.lastname: Movérare
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: J
authors.initials: J
authors.lastname: Hillert
authors.forename: A
authors.initials: A
authors.lastname: Fogdell-Hahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology* / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab; D011237:Predictive Value of Tests; D012698:Serologic Tests; D013548:Sweden; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D000069442:Natalizumab