RT Journal Article
SR Electronic
T1 Serum IL-17F does not predict poor response to IM IFNβ-1a in relapsing-remitting MS
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 531
OP 537
DO 10.1212/WNL.0b013e318259e123
VO 79
IS 6
A1 S.E. Bushnell
A1 Z. Zhao
A1 C.C. Stebbins
A1 D. Cadavid
A1 A.M. Buko
A1 E.T. Whalley
A1 J.A. Davis
A1 E.M. Versage
A1 J.R. Richert
A1 R.C. Axtell
A1 L. Steinman
A1 R. Medori
YR 2012
UL http://n.neurology.org/content/79/6/531.abstract
AB Objective: There is a significant unmet need for serum biomarkers in relapsing-remitting multiple sclerosis (RRMS) that are predictive of therapeutic response to disease-modifying therapies. Following a recent Stanford study which reported that pretreatment levels of serum interleukin (IL)-17F could predict poor response to interferon-β (IFNβ) therapy, we sought to validate the finding using samples from a large clinical trial. Methods: The validation cohort included 54 good responders (GR) and 64 poor responders (PR) selected from 762 subjects with RRMS from the IM IFNβ-1a dose comparison study (Avonex study C94-805). Subjects were classified as GR and PR based on the number of relapses, Expanded Disability Status Scale score, and new and enlarging T2 lesions on MRI. Serum samples were assayed for IL-17F using a multiplexed Luminex assay and for IL-17F/F using an ELISA. Replicate aliquots from the Stanford study were also assayed to assure reproducibility of methods. Results: Median pretreatment and post-treatment serum IL-17F levels were not statistically significantly different between GR and PR, and serum IL-7/IL-17F ratios were also not predictive of response status. Replicate aliquots from the Stanford study showed good correlation to their original cohort (r = 0.77). Conclusions: We were unable to validate the finding that serum IL-17F is a predictor of PR in a large independent cohort of subjects with RRMS. Differences in patient populations and methodology might explain the failure to validate the results from the Stanford study. EAE=experimental autoimmune encephalomyelitis; EDSS=Expanded Disability Status Scale; GR=good responders; HV=healthy volunteer; IFNβ=interferon-β; IL=interleukin; MS=multiple sclerosis; NAb=neutralizing antibody; PR=poor responders; RRMS=relapsing-remitting multiple sclerosis; SLE=systemic lupus erythematosus