Methotrexate markedly reduces the expression of vascular E-selectin, cutaneous lymphocyte-associated antigen and the numbers of mononuclear leucocytes in psoriatic skin

2.50
Hdl Handle:
http://hdl.handle.net/2336/14468
Title:
Methotrexate markedly reduces the expression of vascular E-selectin, cutaneous lymphocyte-associated antigen and the numbers of mononuclear leucocytes in psoriatic skin
Authors:
Sigmundsdottir, Hekla; Johnston, Andrew; Gudjonsson, Johann Eli; Bjarnason, Bolli; Valdimarsson, Helgi
Citation:
Exp. Dermatol. 2004, 13(7):426-34
Issue Date:
1-Jul-2004
Abstract:
A positive correlation between disease severity and the frequency of cutaneous lymphocyte-associated antigen (CLA)-positive T cells in the blood of untreated patients with psoriasis has been previously observed. A dose-dependent inverse relationship between disease severity and the frequency of circulating CLA(+) T cells in psoriasis patients on methotrexate (MTX) treatment is reported. Circulating T cells from a patient with psoriasis were monitored for CLA expression on a daily basis for 5 weeks. A decrease in the intensity and frequency of CLA(+) mononuclear leucocytes was consistently observed in the blood during the first 3-4 days after each MTX intake, but the CLA expression increased thereafter until the next weekly dose was taken. The MTX treatment of this patient was then discontinued for 16 days, and a marked subjective exacerbation was reported within 9 days, which was confirmed objectively (laser Doppler perfusion imaging) after 11 and 16 days. Biopsies taken 4 days after the last MTX intake showed only a few mononuclear leucocytes in lesional skin, but the exacerbation coincided with a marked increase in CLA expression by mononuclear blood leucocytes, followed by an increase in endothelial E-selectin and a striking influx of CLA(+) mononuclear cells into lesional skin. Conversely, a clinical improvement after the patient resumed the MTX treatment was associated with reduction in CLA expression by mononuclear cells in the blood, downregulation of endothelial E-selectin and an approximate threefold decrease in mononuclear leucocyte infiltration of lesional skin. No MTX-associated changes were detected in the expression of very late antigen-4, vascular cell-adhesion molecule-1 nor the late activation marker CD25. It is concluded that MTX decreases the expression of CLA and E-selectin and that this may be a major mechanism for the therapeutic effect of MTX on psoriatic skin lesions.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www.blackwell-synergy.com/doi/abs/10.1111/j.0906-6705.2004.00177.x

Full metadata record

DC FieldValue Language
dc.contributor.authorSigmundsdottir, Hekla-
dc.contributor.authorJohnston, Andrew-
dc.contributor.authorGudjonsson, Johann Eli-
dc.contributor.authorBjarnason, Bolli-
dc.contributor.authorValdimarsson, Helgi-
dc.date.accessioned2007-11-05T14:27:11Z-
dc.date.available2007-11-05T14:27:11Z-
dc.date.issued2004-07-01-
dc.date.submitted2007-11-05-
dc.identifier.citationExp. Dermatol. 2004, 13(7):426-34en
dc.identifier.issn0906-6705-
dc.identifier.pmid15217363-
dc.identifier.doi10.1111/j.0906-6705.2004.00177.x-
dc.identifier.otherAAI12-
dc.identifier.urihttp://hdl.handle.net/2336/14468-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractA positive correlation between disease severity and the frequency of cutaneous lymphocyte-associated antigen (CLA)-positive T cells in the blood of untreated patients with psoriasis has been previously observed. A dose-dependent inverse relationship between disease severity and the frequency of circulating CLA(+) T cells in psoriasis patients on methotrexate (MTX) treatment is reported. Circulating T cells from a patient with psoriasis were monitored for CLA expression on a daily basis for 5 weeks. A decrease in the intensity and frequency of CLA(+) mononuclear leucocytes was consistently observed in the blood during the first 3-4 days after each MTX intake, but the CLA expression increased thereafter until the next weekly dose was taken. The MTX treatment of this patient was then discontinued for 16 days, and a marked subjective exacerbation was reported within 9 days, which was confirmed objectively (laser Doppler perfusion imaging) after 11 and 16 days. Biopsies taken 4 days after the last MTX intake showed only a few mononuclear leucocytes in lesional skin, but the exacerbation coincided with a marked increase in CLA expression by mononuclear blood leucocytes, followed by an increase in endothelial E-selectin and a striking influx of CLA(+) mononuclear cells into lesional skin. Conversely, a clinical improvement after the patient resumed the MTX treatment was associated with reduction in CLA expression by mononuclear cells in the blood, downregulation of endothelial E-selectin and an approximate threefold decrease in mononuclear leucocyte infiltration of lesional skin. No MTX-associated changes were detected in the expression of very late antigen-4, vascular cell-adhesion molecule-1 nor the late activation marker CD25. It is concluded that MTX decreases the expression of CLA and E-selectin and that this may be a major mechanism for the therapeutic effect of MTX on psoriatic skin lesions.en
dc.language.isoenen
dc.publisherMunksgaarden
dc.relation.urlhttp://www.blackwell-synergy.com/doi/abs/10.1111/j.0906-6705.2004.00177.xen
dc.subject.meshAntigens, CDen
dc.subject.meshAntigens, Neoplasmen
dc.subject.meshDermatologic Agentsen
dc.subject.meshE-Selectinen
dc.subject.meshImmunohistochemistryen
dc.subject.meshIntercellular Adhesion Molecule-1en
dc.subject.meshLeukocytesen
dc.subject.meshMembrane Glycoproteinsen
dc.subject.meshMethotrexateen
dc.subject.meshPsoriasisen
dc.titleMethotrexate markedly reduces the expression of vascular E-selectin, cutaneous lymphocyte-associated antigen and the numbers of mononuclear leucocytes in psoriatic skinen
dc.typeArticleen
dc.identifier.journalExperimental dermatologyen
dc.format.digYES-
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