title: Excessive biologic response to IFNβ is associated with poor treatment response in patients with multiple sclerosis.
abstract: BACKGROUND
  Interferon-beta (IFNβ) is used to inhibit disease activity in multiple sclerosis (MS), but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified.
  
  
  METHODS
  The relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70) or poor response (n = 15). Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs).
  
  
  RESULTS
  The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual 'IFN response fingerprint'. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections.
  
  
  CONCLUSIONS
  MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients.
authors: Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, United States of America. rudickr@ccf.org
authors: Richard A
authors: RA
authors: Rudick
authors: M R Sandhya
authors: MR
authors: Rani
authors: Yaomin
authors: Y
authors: Xu
authors: Jar-Chi
authors: JC
authors: Lee
authors: Jie
authors: J
authors: Na
authors: Jennifer
authors: J
authors: Shrock
authors: Anupama
authors: A
authors: Josyula
authors: Elizabeth
authors: E
authors: Fisher
authors: Richard M
authors: RM
authors: Ransohoff
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