PT  - JOURNAL ARTICLE
AU  - Hegen, Harald
AU  - Adrianto, Indra
AU  - Lessard, Christopher J.
AU  - Millonig, Alban
AU  - Bertolotto, Antonio
AU  - Comabella, Manuel
AU  - Giovannoni, Gavin
AU  - Guger, Michael
AU  - Hoelzl, Martina
AU  - Khalil, Michael
AU  - Fazekas, Franz
AU  - Killestein, Joep
AU  - Lindberg, Raija L.P.
AU  - Malucchi, Simona
AU  - Mehling, Matthias
AU  - Montalban, Xavier
AU  - Rudzki, Dagmar
AU  - Schautzer, Franz
AU  - Sellebjerg, Finn
AU  - Sorensen, Per Soelberg
AU  - Deisenhammer, Florian
AU  - Steinman, Lawrence
AU  - Axtell, Robert C.
TI  - Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients
AID  - 10.1212/NXI.0000000000000202
DP  - 2016 Apr 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e202
VI  - 3
IP  - 2
4099  - http://nn.neurology.org/content/3/2/e202.short
4100  - http://nn.neurology.org/content/3/2/e202.full
SO  - Neurol Neuroimmunol Neuroinflamm2016 Apr 01; 3
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