Early identification of interferon-beta responders by ex vivo testing in patients with multiple sclerosis

TY - JOUR

T1 - Early identification of interferon-beta responders by ex vivo testing in patients with multiple sclerosis

AU - Wiesemann, Elke

AU - Deb-Chatterji, Milani

AU - Hemmer, Bernhard

AU - Radeke, Heinfried H

AU - Windhagen, Anja

PY - 2008/9

Y1 - 2008/9

N2 - Interferon-beta (IFN-beta) is an effective treatment for a subgroup of patients with multiple sclerosis (MS). The mechanism of action as well as the pathophysiological basis of responsiveness to IFN-beta is not well understood. To improve treatment considerations in MS patients predictive markers for response to IFN-beta therapy at early timepoints are needed. Here we correlated changes in serum cytokine levels (IL-13, IL-10, IL-5, IL-4, IFN-gamma) with the clinical response to IFN-beta treatment. Serum cytokine levels of 77 untreated and 43 IFN-beta treated relapsing-remitting MS patients (RRMS) were measured by ELISA, including longitudinal measurements in 17 patients. We found a significant upregulation of IL-10 and IL-5 serum cytokine levels during IFN-beta therapy. However, clinical response was only associated with IL-10 serum levels (p=0.038; positive predictive value 0.95, negative predictive value 0.43) but not with IL-5. The predictive power was increased by a combined testing of IL-10 with expression of co-signaling molecules on monocytes, that were previously shown to change during IFN-beta therapy. In a subgroup of 17 patients testing of 4 markers had a positive and negative predictive value of 1.0 for at least 2 of these markers being positive in treatment responders. The results suggest that serum IL-10 is useful to predict treatment response to IFN-beta particularly in combination with a panel of other IFN-beta dependent parameters.

AB - Interferon-beta (IFN-beta) is an effective treatment for a subgroup of patients with multiple sclerosis (MS). The mechanism of action as well as the pathophysiological basis of responsiveness to IFN-beta is not well understood. To improve treatment considerations in MS patients predictive markers for response to IFN-beta therapy at early timepoints are needed. Here we correlated changes in serum cytokine levels (IL-13, IL-10, IL-5, IL-4, IFN-gamma) with the clinical response to IFN-beta treatment. Serum cytokine levels of 77 untreated and 43 IFN-beta treated relapsing-remitting MS patients (RRMS) were measured by ELISA, including longitudinal measurements in 17 patients. We found a significant upregulation of IL-10 and IL-5 serum cytokine levels during IFN-beta therapy. However, clinical response was only associated with IL-10 serum levels (p=0.038; positive predictive value 0.95, negative predictive value 0.43) but not with IL-5. The predictive power was increased by a combined testing of IL-10 with expression of co-signaling molecules on monocytes, that were previously shown to change during IFN-beta therapy. In a subgroup of 17 patients testing of 4 markers had a positive and negative predictive value of 1.0 for at least 2 of these markers being positive in treatment responders. The results suggest that serum IL-10 is useful to predict treatment response to IFN-beta particularly in combination with a panel of other IFN-beta dependent parameters.

KW - Adult

KW - Antigens, CD

KW - Antigens, CD40

KW - Antigens, CD86

KW - Cytokines

KW - Female

KW - Humans

KW - Intercellular Signaling Peptides and Proteins

KW - Interferon-beta

KW - Interleukin-10

KW - Male

KW - Middle Aged

KW - Monocytes

KW - Multiple Sclerosis

KW - Programmed Cell Death 1 Ligand 2 Protein

KW - Up-Regulation

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.clim.2008.04.007

DO - 10.1016/j.clim.2008.04.007

M3 - SCORING: Journal article

C2 - 18539537

VL - 128

SP - 306

EP - 313

JO - CLIN IMMUNOL

JF - CLIN IMMUNOL

SN - 1521-6616

IS - 3

ER -