Early identification of interferon-beta responders by ex vivo testing in patients with multiple sclerosis
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Early identification of interferon-beta responders by ex vivo testing in patients with multiple sclerosis. / Wiesemann, Elke; Deb-Chatterji, Milani; Hemmer, Bernhard; Radeke, Heinfried H; Windhagen, Anja.
In: CLIN IMMUNOL, Vol. 128, No. 3, 09.2008, p. 306-13.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -