Key result
Poor clinical response to IFNβ is linked to exaggerated molecular responses in ~82% of regulated genes.
Why the study?
Does the molecular response to IFNβ correlate with treatment response in patients with multiple sclerosis?
Cohort (n=85)
No
Does the molecular response to IFNβ correlate with treatment response in patients with multiple sclerosis?
p-value: p=<0.001
An exaggerated molecular response to IFNβ is associated with poor treatment response in MS patients, suggesting a potential biomarker for personalized therapy.
Exaggerated early molecular response to IFNβ was associated with poor clinical response in MS; hypothesis-generating for biomarker-guided therapy.
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. CONCLUSION: 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.
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Rudick et al. (2011) conducted a cohort in Multiple Sclerosis (n=85). Interferon-beta-1a vs. Good responders was evaluated on Proportion of regulated genes showing an exaggerated molecular response in poor responders at first injection (p=<0.001). Patients with a poor clinical response to IFNβ treatment exhibited a significantly exaggerated molecular response, with 82% of regulated genes showing an exaggerated response at the first injection.