Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients

Harald Hegen; Indra Adrianto; Christopher J Lessard; Alban Millonig; Antonio Bertolotto; Manuel Comabella; Gavin Giovannoni; Michael Guger; Martina Hoelzl; Michael Khalil; Franz Fazekas; Joep Killestein; Raija L P Lindberg; Simona Malucchi; Matthias Mehling; Xavier Montalbán; Dagmar Rudzki; Franz Schautzer; Finn Sellebjerg; Per Soelberg Sorensen; Florian Deisenhammer; Lawrence Steinman; Robert C Axtell

doi:10.1212/NXI.0000000000000202

Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients

Harald Hegen, Indra Adrianto, Christopher J Lessard, Alban Millonig, Antonio Bertolotto, Manuel Comabella, Gavin Giovannoni, Michael Guger, Martina Hoelzl, Michael Khalil, Franz Fazekas, Joep Killestein, Raija L P Lindberg, Simona Malucchi, Matthias Mehling, Xavier Montalbán, Dagmar Rudzki, Franz Schautzer, Finn Sellebjerg, Per Soelberg SorensenFlorian Deisenhammer, Lawrence Steinman, Robert C Axtell

Department of Clinical Medicine

21 Citations (Scopus)

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Abstract

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-b 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-b response.

Original language	English
Article number	e202
Journal	Neurology: Neuroimmunology & Neuroinflammation
Volume	3
Issue number	2
Number of pages	11
ISSN	2332-7812
DOIs	https://doi.org/10.1212/NXI.0000000000000202
Publication status	Published - 1 Apr 2016

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Hegen, H., Adrianto, I., Lessard, C. J., Millonig, A., Bertolotto, A., Comabella, M., Giovannoni, G., Guger, M., Hoelzl, M., Khalil, M., Fazekas, F., Killestein, J., Lindberg, R. L. P., Malucchi, S., Mehling, M., Montalbán, X., Rudzki, D., Schautzer, F., Sellebjerg, F., ... Axtell, R. C. (2016). Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients. Neurology: Neuroimmunology & Neuroinflammation, 3(2), Article e202. https://doi.org/10.1212/NXI.0000000000000202

Hegen, H, Adrianto, I, Lessard, CJ, Millonig, A, Bertolotto, A, Comabella, M, Giovannoni, G, Guger, M, Hoelzl, M, Khalil, M, Fazekas, F, Killestein, J, Lindberg, RLP, Malucchi, S, Mehling, M, Montalbán, X, Rudzki, D, Schautzer, F, Sellebjerg, F , Sorensen, PS, Deisenhammer, F, Steinman, L & Axtell, RC 2016, 'Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients', Neurology: Neuroimmunology & Neuroinflammation, vol. 3, no. 2, e202. https://doi.org/10.1212/NXI.0000000000000202

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title = "Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients",

abstract = "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-b 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-b response.",

author = "Harald Hegen and Indra Adrianto and Lessard, {Christopher J} and Alban Millonig and Antonio Bertolotto and Manuel Comabella and Gavin Giovannoni and Michael Guger and Martina Hoelzl and Michael Khalil and Franz Fazekas and Joep Killestein and Lindberg, {Raija L P} and Simona Malucchi and Matthias Mehling and Xavier Montalb{\'a}n and Dagmar Rudzki and Franz Schautzer and Finn Sellebjerg and Sorensen, {Per Soelberg} and Florian Deisenhammer and Lawrence Steinman and Axtell, {Robert C}",

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doi = "10.1212/NXI.0000000000000202",

language = "English",

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T1 - Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients

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 - Montalbán, Xavier

AU - Rudzki, Dagmar

AU - Schautzer, Franz

AU - Sellebjerg, Finn

AU - Sorensen, Per Soelberg

AU - Deisenhammer, Florian

AU - Steinman, Lawrence

AU - Axtell, Robert C

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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-b 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-b response.

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-b 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-b response.

U2 - 10.1212/NXI.0000000000000202

DO - 10.1212/NXI.0000000000000202

M3 - Journal article

C2 - 26894205

SN - 2332-7812

VL - 3

JO - Neurology: Neuroimmunology & Neuroinflammation

JF - Neurology: Neuroimmunology & Neuroinflammation

IS - 2

M1 - e202

ER -

Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients

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