title: Interferon inhibitory activity in patients with multiple sclerosis.
abstract: BACKGROUND
  Interferon inhibitory activity (IIA) is a logical candidate for explaining neutralizing antibody-negative partial responsiveness to interferon beta in multiple sclerosis (MS), but its role has not been evaluated.
  
  
  OBJECTIVE
  To investigate the role of IIA and soluble interferon-alpha/beta receptor (sIFNR) in determining response of patients with MS to interferon beta therapy.
  
  
  METHODS
  Parallel-group, open-label study.
  
  
  METHODS
  Baird Multiple Sclerosis Center, Buffalo, NY. Patients Blood was obtained before and 24 hours after injection of interferon beta-1a from 38 anti-interferon beta neutralizing antibody-negative patients with relapsing-remitting MS and 16 untreated healthy controls. On the basis of clinical parameters of response to interferon beta therapy, the patients were divided into stable or good-responder (n = 20) and active or partial-responder (n = 18) groups.
  
  
  METHODS
  Quantitative analyses of magnetic resonance imaging were obtained; the IIA and sIFNR levels were measured using bioassay and enzyme-linked immunosorbent assay, respectively.
  
  
  RESULTS
  The IIA and sIFNR levels were elevated in MS patients compared with controls (P<.001). The IIA levels were higher in active or partial responders compared with stable or good responders (P<.001); the sIFNR levels were not different between groups. The Extended Disability Status Score and T2 lesion volumes were higher in the active or partial-responder group compared with the stable or good-responder group. Interferon beta-1a did not have short-term effects on the IIA and sIFNR levels. In univariate general linear model and stepwise regression analyses, IIA levels were associated with T2 lesion volume.
  
  
  CONCLUSIONS
  The levels of IIA are associated with increased MS disease activity and with responsiveness to interferon beta therapy in anti-interferon beta neutralizing antibody-negative MS patients.
authors.affiliation: Department of Cell and Molecular Biology, Roswell Park Cancer Institute, Jacobs Neurological Institute, , Buffalo, New York 14263, USA. Kailash.Chadha@RoswellPark.org
authors.forename: Kailash
authors.initials: K
authors.lastname: Chadha
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.forename: Kavitha
authors.initials: K
authors.lastname: Bhasi
authors.forename: Jason
authors.initials: J
authors.lastname: Muhitch
authors.forename: Joan
authors.initials: J
authors.lastname: Feichter
authors.forename: Miriam
authors.initials: M
authors.lastname: Tamaño-Blanco
authors.forename: Nadir
authors.initials: N
authors.lastname: Abdelrahman
authors.forename: Julian
authors.initials: J
authors.lastname: Ambrus
authors.forename: Frederick
authors.initials: F
authors.lastname: Munschauer
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D016022:Case-Control Studies; D002460:Cell Line; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D017471:Receptors, Interferon / Q000037:antagonists & inhibitors* / Q000097:blood; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D000906:Antibodies; D017471:Receptors, Interferon; D001613:beta 2-Microglobulin; D016899:Interferon-beta; D000068556:Interferon beta-1a