RT Journal Article
SR Electronic
T1 Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e202
DO 10.1212/NXI.0000000000000202
VO 3
IS 2
A1 Hegen, Harald
A1 Adrianto, Indra
A1 Lessard, Christopher J.
A1 Millonig, Alban
A1 Bertolotto, Antonio
A1 Comabella, Manuel
A1 Giovannoni, Gavin
A1 Guger, Michael
A1 Hoelzl, Martina
A1 Khalil, Michael
A1 Fazekas, Franz
A1 Killestein, Joep
A1 Lindberg, Raija L.P.
A1 Malucchi, Simona
A1 Mehling, Matthias
A1 Montalban, Xavier
A1 Rudzki, Dagmar
A1 Schautzer, Franz
A1 Sellebjerg, Finn
A1 Sorensen, Per Soelberg
A1 Deisenhammer, Florian
A1 Steinman, Lawrence
A1 Axtell, Robert C.
YR 2016
UL http://nn.neurology.org/content/3/2/e202.abstract
AB Objective: To evaluate serum cytokine profiles for their utility to determine the heterogeneous responses to interferon (IFN)–β treatment in patients with multiple sclerosis (MS).Methods: Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome receiving de novo IFN-β treatment were included in this prospective, observational study. Number of relapses and changes in disability were assessed 2 years prior to and 2 years after initiation of treatment. Sera were collected at baseline and after 3 months on therapy. Cytokine levels in sera were assessed by Luminex multiplex assays. Baseline cytokine profiles were grouped by hierarchical clustering analysis. Demographic features, changes in cytokines, and clinical outcome were then assessed in the clustered patient groups.Results: A total of 157 patients were included in the study and clustered into 6 distinct subsets by baseline cytokine profiles. These subsets differed significantly in their clinical and biological response to IFN-β therapy. Two subsets were associated with patients who responded poorly to therapy. Two other subsets, associated with a good response to therapy, showed a significant reduction in relapse rates and no worsening of disability. Each subset also had differential changes in cytokine levels after 3 months of IFN-β treatment.Conclusions: There is heterogeneity in the immunologic pathways of the RRMS population, which correlates with IFN-β response.CIS=clinically isolated syndrome; CV=coefficient of variation; DMT=disease-modifying therapy; EDSS=Expanded Disability Status Scale; HDMP=high-dose methylprednisolone; IFN=interferon; IL=interleukin; MCP1=monocyte chemoattractant protein-1; MIP=macrophage inflammatory protein; MS=multiple sclerosis; MxA=myxovirus protein A; NAb=neutralizing antibodies; NMO=neuromyelitis optica; RRMS=relapsing-remitting multiple sclerosis; SC=subcutaneous; sTRAIL=soluble tumor necrosis factor-related apoptosis-inducing ligand; sVCAM=soluble vascular cell adhesion molecule