Multiparameter flow cytometry as a tool to evaluate antipsoriatic therapy. 1997

C P Glade, and P E van Erp, and J B Boezeman, and P C van de Kerkhof
Department of Dermatology, University Hospital Nijmegen, The Netherlands.

Objective comparison of different antipsoriatic therapies requires quantitative assessment of disease severity. However, clinical assessment with the widely used Psoriasis Area and Severity Index (PASI) introduces inaccuracy. An alternative is the quantitative analysis of different epidermal cell parameters using multiparameter flow cytometry. Our aim in the present study was to compare the clinical and flow cytometric approach to monitor disease activity and to evaluate antipsoriatic efficacy. Clinical scores for erythema, induration and scaling were assessed and biopsies for flow cytometric analysis were obtained from the psoriatic plaques of 89 patients before and after treatment with different therapeutic regimens consisting of vitamin D3 analogues and corticosteroids. In total, 219 epidermal cell suspensions were analysed using triple-labelling, with the simultaneous staining of markers for epidermal proliferation (DNA dye TO-PRO-3), differentiation (antikeratin 10), and inflammation (antivimentin). Correlation analysis was performed on 166 paired values obtained from 83 patients. A highly significant correlation was observed between erythema and the percentage of vimentin-positive cells, between scaling and the percentage of keratin 10 positive keratinocytes, and between induration and the number of basal keratinocytes in the S- and G2M phase, when all 166 biopsies were assessed. The correlation remained in the same range if the analysis was restricted to the 83 pretreatment biopsies. In contrast to the clinical scores, the flow cytometric analysis permitted a clear separation between the antiproliferative and anti-inflammatory or keratinization-enhancing effects of antipsoriatic treatment. The vitamin D3 analogues proved to exert a mainly antiproliferative effect. The combination of calcipotriol and a topical corticosteroid improved all cell biological markers substantially, and clobetasol monotherapy had a powerful effect on these markers. In conclusion, multiparameter flow cytometry has been shown to be a sensitive tool to evaluate the growth inhibiting, anti-inflammatory and keratinization-enhancing effects of antipsoriatic therapies.

UI MeSH Term Description Entries
D007633 Keratins A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION. Cytokeratin,Keratin Associated Protein,Keratin,Keratin-Associated Proteins,alpha-Keratin,Associated Protein, Keratin,Keratin Associated Proteins,Protein, Keratin Associated,alpha Keratin
D011565 Psoriasis A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. Palmoplantaris Pustulosis,Pustular Psoriasis of Palms and Soles,Pustulosis Palmaris et Plantaris,Pustulosis of Palms and Soles,Psoriases
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D004817 Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of EPITHELIUM: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).
D004890 Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Erythemas
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012720 Severity of Illness Index Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder. Illness Index Severities,Illness Index Severity
D014746 Vimentin An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000.
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune

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