The potential of the skin as a readout system to test artificial turf systems: clinical and immunohistological effects of a sliding on natural grass and artificial turf.

The purpose of this study was to investigate the interaction of skin with natural grass and artificial turf at clinical, histological and immunohistochemical level. Therefore, 14 male volunteers performed slidings on dry natural grass, wet natural grass and artificial turf. Directly and 24 h after the slidings, a clinical picture and a 3-mm punch biopsy of the lesion were taken. Paraffin sections (6 µm) were hematoxylin-eosin stained. Immunohistochemistry was performed for CD3, hBD-2, K16, K10, Ki67 and HSP70. Clinically, a sliding performed on artificial turf caused less erythema but more abrasion compared to natural grass. At histological level, artificial turf or dry natural grass damaged the stratum corneum the most. Directly after the sliding, CD3, hBD-2, K16, K10, Ki67 and HSP70 expression was normal. 24 h after a sliding on artificial turf or dry natural grass, an increase of K16, hBD-2 and HSP70 expression was observed. In this pilot study it was not possible to clearly distinguish between skin damage induced by a sliding on artificial turf and natural grass. However, small differences at clinical and histological level seem to exist. This demonstrates the potential of the skin as readout system to evaluate artificial turf systems and mechanical skin damage.

Relevance of compartmentalization of T-cell subsets for clinical improvement in psoriasis: effect of immune-targeted antipsoriatic therapies.

BACKGROUND: Therapies targeting the T cell-mediated pathology of psoriasis have been found to achieve remarkable clinical improvement and have confirmed the crucial role of the immune system either in peripheral blood (PB) or in skin. No analyses of T-cell counts in both compartments have been conducted in order to confirm or refute the hypothesized shifts between them. OBJECTIVES: To gain more insight in the dynamics of compartmentalization of T cells between PB and lesional skin of patients with psoriasis, in response to immune-targeted antipsoriatic therapies. METHODS: Eighteen patients with psoriasis received either efalizumab (n = 9) or etanercept (n = 9) for 12 weeks. Biopsies were taken for immunohistochemical analysis of T-cell subsets and simultaneously T-cell subsets were isolated from PB specimens by flow cytometry. RESULTS: The Psoriasis Area and Severity Index declined significantly after 12 weeks of etanercept, but not for efalizumab. After treatment with efalizumab, a significantly decreased number of all T-cell subsets was found in the dermis. In the epidermis, CD4+, CD8+, CD25+, CD45RO+ and CD161+ T-cell subsets were significantly decreased. With respect to etanercept, few significant changes in T-cell subsets were found. The percentage of lymphocytes in PB was significantly elevated after efalizumab treatment regardless of responder status. CONCLUSIONS: Treatment with efalizumab establishes successful recompartmentalization of T-cell subsets with modest clinical efficacy after 12 weeks, whereas in etanercept-treated patients, a significant clinical response is no guarantee for significant changes in T-cell subsets in the different compartments. Reductions in T-cell subsets cannot be used as predictive markers for the clinical response to therapy. Interference with the studied T-cell populations in its own right seems not to be responsible for the clinical efficacy of efalizumab and etanercept.

Lymphocyte subsets in peripheral blood of patients with moderate-to-severe versus mild plaque psoriasis.

In several studies peripheral blood T-cells have been quantified, yet few data are available on lymphocyte subsets in moderate-to-severe psoriasis (in terms of extent and activity of lesions) versus mild psoriasis. The objective is to compare lymphocyte subsets in peripheral blood of patients with moderate-to-severe disease (PASI-score > or =12) to patients with mild disease (PASI-score <12) and to healthy subjects. By means of flow cytometry method, lymphocytes in peripheral blood of 27 patients with psoriasis and 10 healthy controls were characterized. The absolute number of total lymphocytes was markedly decreased in patients with moderate-to-severe psoriasis as compared to patients with mild disease and normal subjects. Cellcounts of all analysed subsets were found to be increased in more severe psoriasis, except for CD8+CD45RO+ cells. The under-representation of CD8+CD45RO+ cells is compatible with the dynamics of acquired immunity, which requires a time log after the relapse of the lesions to differentiate from CD45RA+ naive cells.

Oral retinoic acid metabolism blocking agent Rambazole for plaque psoriasis: an immunohistochemical study.

BACKGROUND: The novel systemic all-trans retinoic acid metabolism blocking agent (RAMBA) R115866 (Rambazole(TM); Barrier Therapeutics, Geel, Belgium; further referred to as rambazole) increases intracellular levels of endogenous all-trans retinoic acid (RA). Well-known effects of RA are normalization of aberrant epithelial growth and differentiation. Hence, rambazole might be beneficial in the treatment of plaque psoriasis. OBJECTIVES: The dynamics of epidermal proliferation, keratinization, lesional T-cell subsets and cells expressing natural killer (NK)-receptors in plaque psoriasis were assessed during treatment with rambazole, as part of a phase IIa open-label clinical trial. METHODS: Six patients were treated with rambazole, 1 mg, once daily, for 8 weeks. At weeks 0, 2 and 8, psoriatic plaque severity scores (SUM) and biopsies from a target lesion were assessed. Epidermal proliferation (Ki67), keratinization markers (K10, K13, K19), T-cell subsets (CD3, CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+, GITR+) and cells expressing NK-receptors (CD94, CD161) were immunohistochemically stained and quantified with image analysis. RESULTS: At week 2 the mean SUM-score was virtually equal to baseline, which was accompanied immunohistochemically by equal epidermal hyperproliferation, a nonsignificant decrease in K10 positive epidermis and, overall, a nonsignificant increase in immunocyte subsets. At week 8, in contrast, plaque severity was reduced by 34% from baseline (P < 0.05). Improvements were also detected for epidermal proliferation (-63%; P < 0.01) and K10 expression (+29%; P < 0.01), compared with baseline. No induction of retinoid-specific keratinization (K13, K19) was observed. A nonsignificant reduction of all pathogenic T-cell subsets and cells expressing NK-receptors was observed at week 8 of treatment (P > 0.05). CONCLUSIONS: Clinical efficacy of rambazole is primarily the result of restoring proliferation (Ki67) and differentiation (K10) of epidermal keratinocytes. Secondly, relevant T-cell subsets and cells expressing NK-receptors showed nonsignificant reductions after 8 weeks of treatment with rambazole.

Therapeutic effects of a 12-week course of alefacept on nail psoriasis.

BACKGROUND AND OBJECTIVES: Nail psoriasis is a common finding in psoriatic patients and it affects the quality of life in a great proportion of patients. Topical or systemic treatments have limited effectiveness or have a serious toxicity potential. Biologicals such as alefacept are the most recent treatment modalities for psoriasis. In the present study we evaluated changes in nail pathology in patients with plaque psoriasis and nail involvement during treatment with alefacept. PATIENTS AND METHODS: Digital photographs from eight patients were produced, which were analysed using the nail psoriasis severity index (NAPSI). A minimal NAPSI of 15 was chosen to divide patients into a moderate to very severe nail psoriasis group and a group with no or mild nail psoriasis. A decrease in NAPSI of at least 25% was considered a significant response to therapy. RESULTS: In the group with at least moderate nail psoriasis, two patients improved, in two patients the nail changes remained unchanged and in one patient the nail pathology was aggravated. The group with no or mild nail psoriasis showed variable results. CONCLUSIONS: Although alefacept showed some results in treating nail pathology in psoriasis, a more extensive study is required, covering both more patients and a more extensive time period. Furthermore, it would also be clinically relevant to compare the effects of alefacept on nail psoriasis with other biologicals.