Effects of interferon-beta on co-signaling molecules:upregulation of CD40, CD86 and PD-L2 on monocytes in relation to clinical response to interferon-beta treatment in patients with multiple sclerosis
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Effects of interferon-beta on co-signaling molecules:upregulation of CD40, CD86 and PD-L2 on monocytes in relation to clinical response to interferon-beta treatment in patients with multiple sclerosis. / Wiesemann, Elke; Deb-Chatterji, Milani; Trebst, Corinna; Hemmer, Bernhard; Stangel, Martin; Windhagen, Anja.
in: MULT SCLER J, Jahrgang 14, Nr. 2, 03.2008, S. 166-76.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Effects of interferon-beta on co-signaling molecules:upregulation of CD40, CD86 and PD-L2 on monocytes in relation to clinical response to interferon-beta treatment in patients with multiple sclerosis
AU - Wiesemann, Elke
AU - Deb-Chatterji, Milani
AU - Trebst, Corinna
AU - Hemmer, Bernhard
AU - Stangel, Martin
AU - Windhagen, Anja
PY - 2008/3
Y1 - 2008/3
N2 - Interferon-beta (IFN-beta) reduces disease activity in a subgroup of patients with relapsing remitting multiple sclerosis (MS). The mechanism of action as well as the pathophysiological basis of responsiveness to IFN-beta is not well understood. Since T-cell activation plays an important part in the pathophysiology of MS, we here investigated the effect of IFN-beta on the expression of co-signaling pathways (CD28-CD80/CD86, CD154-CD40, ICOS-ICOSL, PD-1-PD-L1/2) in MS patients and correlated the results with the clinical response to IFN-beta in individual patients. Expression of co-signaling molecules was measured by flow cytometry in vitro on peripheral blood mononuclear cells after incubation with IFN-beta, and in vivo in whole blood samples of 32 untreated and 24 IFN-beta treated MS patients, including 13 patients longitudinal. IFN-beta treatment induced upregulation of CD40, CD80, CD86, PD-L1 and PD-L2 on monocytes as well as PD-L1 on CD4+-T-cells in vitro and in vivo. IFN-beta treated MS patients were grouped into responders and non-responders on the basis of Kurtzkés EDSS (expanded disability status scale) progression and relapse rate. Upregulation of CD40, CD86 and PD-L2 on monocytes was associated with treatment response to IFN-beta (P < 0.001, P = 0.028 and P = 0.028, respectively). Our results show that IFN-beta upregulates co-stimulatory as well as co-inhibitory molecules in vitro and in vivo implicating that modulation of the balance between positive and negative co-stimulatory signals might be an important part of the mechanism of action of IFN-beta in MS. Upregulation of the expression of CD40, CD86 and PD-L2 may be useful as a predictive marker for clinical response to IFN-beta treatment at early timepoints during IFN-beta therapy.
AB - Interferon-beta (IFN-beta) reduces disease activity in a subgroup of patients with relapsing remitting multiple sclerosis (MS). The mechanism of action as well as the pathophysiological basis of responsiveness to IFN-beta is not well understood. Since T-cell activation plays an important part in the pathophysiology of MS, we here investigated the effect of IFN-beta on the expression of co-signaling pathways (CD28-CD80/CD86, CD154-CD40, ICOS-ICOSL, PD-1-PD-L1/2) in MS patients and correlated the results with the clinical response to IFN-beta in individual patients. Expression of co-signaling molecules was measured by flow cytometry in vitro on peripheral blood mononuclear cells after incubation with IFN-beta, and in vivo in whole blood samples of 32 untreated and 24 IFN-beta treated MS patients, including 13 patients longitudinal. IFN-beta treatment induced upregulation of CD40, CD80, CD86, PD-L1 and PD-L2 on monocytes as well as PD-L1 on CD4+-T-cells in vitro and in vivo. IFN-beta treated MS patients were grouped into responders and non-responders on the basis of Kurtzkés EDSS (expanded disability status scale) progression and relapse rate. Upregulation of CD40, CD86 and PD-L2 on monocytes was associated with treatment response to IFN-beta (P < 0.001, P = 0.028 and P = 0.028, respectively). Our results show that IFN-beta upregulates co-stimulatory as well as co-inhibitory molecules in vitro and in vivo implicating that modulation of the balance between positive and negative co-stimulatory signals might be an important part of the mechanism of action of IFN-beta in MS. Upregulation of the expression of CD40, CD86 and PD-L2 may be useful as a predictive marker for clinical response to IFN-beta treatment at early timepoints during IFN-beta therapy.
KW - Adult
KW - Antibodies
KW - Antigens, CD
KW - Antigens, CD274
KW - Antigens, CD40
KW - Antigens, CD86
KW - CD4-Positive T-Lymphocytes
KW - Female
KW - Flow Cytometry
KW - Humans
KW - Immunologic Factors
KW - Intercellular Signaling Peptides and Proteins
KW - Interferon-beta
KW - Male
KW - Middle Aged
KW - Monocytes
KW - Multiple Sclerosis, Relapsing-Remitting
KW - Programmed Cell Death 1 Ligand 2 Protein
KW - STAT1 Transcription Factor
KW - Up-Regulation
KW - Controlled Clinical Trial
KW - Journal Article
U2 - 10.1177/1352458507081342
DO - 10.1177/1352458507081342
M3 - SCORING: Journal article
C2 - 17942524
VL - 14
SP - 166
EP - 176
JO - MULT SCLER J
JF - MULT SCLER J
SN - 1352-4585
IS - 2
ER -