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- Titel:
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.
- Dokumenttyp:
- Journal Article
- Autor(en):
- Wiesemann, E; Deb, M; Trebst, C; Hemmer, B; Stangel, M; Windhagen, A
- Abstract:
- 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. Multiple Sclerosis 2008; 14: 166-176. http://msj.sagepub.com.
- Zeitschriftentitel:
- Mult Scler
- Jahr:
- 2008
- Band / Volume:
- 14
- Heft / Issue:
- 2
- Seitenangaben Beitrag:
- 166-76
- Sprache:
- eng
- Volltext / DOI:
- doi:10.1177/1352458507081342
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/17942524
- Print-ISSN:
- 1352-4585
- TUM Einrichtung:
- Neurologische Klinik und Poliklinik
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