Early identification of interferon-beta responders by ex vivo testing in patients with multiple sclerosis.
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.
Department of Neurology, Medical School Hannover, Carl-Neuberg-Str 1, 30625 Hannover, Germany. wiesemann.elke@mh-hannover.de
Elke
E
Wiesemann
Milani
M
Deb
Bernhard
B
Hemmer
Heinfried H
HH
Radeke
Anja
A
Windhagen
D000328:Adult; D015703:Antigens, CD / Q000097:blood; D051940:B7-2 Antigen / Q000097:blood; D019013:CD40 Antigens / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D016899:Interferon-beta / Q000097:blood / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D015854:Up-Regulation
D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D016753:Interleukin-10; D016899:Interferon-beta