title: Methotrexate markedly reduces the expression of vascular E-selectin, cutaneous lymphocyte-associated antigen and the numbers of mononuclear leucocytes in psoriatic skin.
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.
authors.affiliation: Department of Immunology, Landspitali University Hospital, 101 Reykjavik, Iceland.
authors.forename: Hekla
authors.initials: H
authors.lastname: Sigmundsdottir
authors.forename: Andrew
authors.initials: A
authors.lastname: Johnston
authors.forename: Johann Eli
authors.initials: JE
authors.lastname: Gudjonsson
authors.forename: Bolli
authors.initials: B
authors.lastname: Bjarnason
authors.forename: Helgi
authors.initials: H
authors.lastname: Valdimarsson
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D002469:Cell Separation; D003879:Dermatologic Agents / Q000494:pharmacology*; D015536:Down-Regulation; D019040:E-Selectin / Q000096:biosynthesis* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000096:biosynthesis; D039041:Integrin alpha4beta1 / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007962:Leukocytes / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008727:Methotrexate / Q000494:pharmacology*; D010477:Perfusion; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism; D018089:Superantigens / Q000737:chemistry; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D003879:Dermatologic Agents; D019040:E-Selectin; D039001:Integrin alpha Chains; D039041:Integrin alpha4beta1; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D018089:Superantigens; D019010:Vascular Cell Adhesion Molecule-1; C091367:alpha E integrins; D018799:Intercellular Adhesion Molecule-1; D008727:Methotrexate