title: Heterogeneous, longitudinally stable molecular signatures in response to interferon-beta.
abstract: Interferons (IFNs) are widely used in therapy for viral, neoplastic, and inflammatory disorders, but clinical response varies among patients. The biological basis for variable clinical response is not known. We determined the primary molecular response to IFN-beta (IFN-beta) injections in 35 treatment-naïve multiple sclerosis (MS) patients using a customized cDNA macroarray with 186 interferon-stimulated genes (ISGs). Our results revealed striking interindividual heterogeneity, both in the magnitude as well as the nature of the primary molecular response to IFN-beta injections. Despite marked between-subject variability in the molecular response, responses within individual subjects were stable over a 6-month interval. Our data suggest that clinical response to IFN-beta therapy for MS differs among patients because of qualitative rather than quantitative variability in the primary molecular response to the drug.
authors.affiliation: Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors.forename: M R Sandhya
authors.initials: MR
authors.lastname: Rani
authors.forename: Yaomin
authors.initials: Y
authors.lastname: Xu
authors.forename: Jar-Chi
authors.initials: JC
authors.lastname: Lee
authors.forename: Jennifer
authors.initials: J
authors.lastname: Shrock
authors.forename: Anupama
authors.initials: A
authors.lastname: Josyula
authors.forename: Joerg
authors.initials: J
authors.lastname: Schlaak
authors.forename: Swathi
authors.initials: S
authors.lastname: Chakraborthy
authors.forename: Nie
authors.initials: N
authors.lastname: Ja
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rudick
mesh_terms: D000328:Adult; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D016899:Interferon-beta