CD56(bright) natural killer cells and response to daclizumab HYP in relapsing-remitting MS

J Elkins; J Sheridan; L Amaravadi; K Riester; K Selmaj; B Bielekova; E Parr; G Giovannoni

doi:10.1212/NXI.0000000000000065

CD56(bright) natural killer cells and response to daclizumab HYP in relapsing-remitting MS

Neurol Neuroimmunol Neuroinflamm. 2015 Jan 22;2(2):e65. doi: 10.1212/NXI.0000000000000065. eCollection 2015 Apr.

Authors

J Elkins¹, J Sheridan¹, L Amaravadi¹, K Riester¹, K Selmaj¹, B Bielekova¹, E Parr¹, G Giovannoni¹

Affiliation

¹ Biogen Idec (J.E., L.A., K.R.), Cambridge, MA; AbbVie Biotherapeutics Inc. (J.S.), Redwood City, CA; Medical University of Lodz (K.S.), Poland; Neuroimmunology Branch (B.B.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Excel Scientific Solutions (E.P.), Southport, CT; and Blizard Institute (G.G.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK.

Abstract

Objective: To assess the relationship between CD56(bright) natural killer (NK) cells and multiple sclerosis (MS) disease activity in patients with relapsing-remitting MS treated with daclizumab high-yield process (DAC HYP).

Methods: Data were from patients enrolled in a 52-week randomized, double-blind, placebo-controlled study of DAC HYP and its extension study. Assessments included relationships of CD56(bright) NK cell numbers (identified using fluorescence-activated cell sorting) at weeks 4 and 8 with the numbers of new or newly enlarging T2-hyperintense lesions between weeks 24 and 52 and the annualized relapse rate.

Results: In DAC HYP-treated patients but not placebo-treated patients, the numbers of CD56(bright) NK cells increased over 52 weeks of treatment, and their numbers at weeks 4 and 8 predicted the number of new or newly enlarging T2-hyperintense lesions between weeks 24 and 52 of treatment (p ≤ 0.005 for each comparison). Similar but nonsignificant trends were observed between CD56(bright) NK cell counts and the annualized relapse rate in DAC HYP-treated patients. DAC HYP-treated patients who showed lower levels of expansion of CD56(bright) NK cells still developed fewer new or newly enlarging T2-hyperintense lesions than placebo-treated patients during the first year of treatment.

Conclusions: CD56(bright) NK cells appear to mediate some of the treatment-related effects of DAC HYP, but their numbers do not account for the full effect of DAC HYP on MS-related outcomes.