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Notes: Summary Background Caveolin-1 is a key structural and functional protein for plasmalemmal invaginations termed caveolae. Caveolin-1 is known to modulate multiple signal-transducing pathways involved in cell differentiation and proliferation. Psoriasis is viewed as a multifactorial pathology characterized by keratinocyte hyperproliferation and abnormal cell maturation. We hypothesized that loss of caveolin-1 within epidermal keratinocytes may contribute to the development and/or progression of the psoriatic phenotype. Objectives To examine the expression and spatial distribution of caveolin-1 in skin biopsies from normal subjects and in patients with psoriasis. Methods Using immunohistochemical methods caveolin-1 protein expression was assayed in two independent patient groups. Firstly, a retrospective analysis was conducted on archival skin samples obtained from nine normal subjects and from involved tissue of 12 patients with psoriasis. Following this, a prospectively designed study was conducted in 10 further patients with active psoriasis and involving caveolin-1 staining of biopsy tissue from the uninvolved, advancing edge and lesional skin tissue from within the same subject. Results In normal skin or uninvolved skin from psoriasis patients intense caveolin-1 staining was present throughout full-thickness epidermis. In 20 of the 22 patient cases (combined retrospective and prospective samples) caveolin-1 protein was significantly reduced and consistently showed very weak or absent staining within the hyperproliferative basal cell layers of the psoriatic plaque (P 〈 0·002 for retrospective archival study and P 〈 0·01 for prospectively designed study). Comparisons between caveolin-1 staining in uninvolved tissue and at the advancing edge of a migrating plaque were more equivocal (P 〉 0·05). Conclusions The findings of this study are consistent with a downregulation of caveolin-1 that may serve as an aetiological factor in the development and/or progression of psoriasis. Further mechanistic investigations are required with the potential that caveolin-1 protein may be a novel target for therapy of psoriasis.

Notes: Background Cytokine production is under genetic control, and certain allelic variants of cytokine genes are associated with higher or lower cytokine production in vitro and in vivo. Psoriasis is associated with an overexpression in the involved skin of T-helper cell type 1 (Th1) cytokines, e.g. interferon (IFN) -γ and tumour necrosis factor (TNF) α and relative underexpression of Th2 cytokines, e.g. interleukin (IL) -4 and IL-10. Objective We investigated the hypothesis that allelic variants of genes for a high production of Th1 cytokines or TNF-α, or conversely low production of Th2 cytokines might represent a risk factor for developing psoriasis. Methods Genotyping for IFN-γ, IL-10, IL-4 and TNF-α was undertaken for 84 patients with psoriasis and compared with control data on file. Results Genotype frequencies showed no differences between patients and controls for IFN-γ, TNF-α or IL-4. For IL-10, patients with late onset psoriasis (over 40 years) were more likely to be heterozygous at position − 1082 (P = 0·02), corresponding to intermediate production of IL-10 in vitro and in vivo. Conclusions Psoriasis is not determined by a genotype consistent with high production of Th1 cytokines or low production of Th2 cytokines. Thus, the Th1 cytokine profile found in psoriatic plaques is most likely a consequence of local factors.

Notes: Background  Psoriasis has a detrimental effect on patients' quality of life. However, there is a relative dearth of information on which aspects of a patient's well-being are affected by successful treatment.Objectives  To investigate whether, and to what extent, improvement in the clinical severity of psoriasis induced by photochemotherapy with psoralen plus ultraviolet A (PUVA) translates into meaningful changes in beliefs about psoriasis, coping, stress, distress or disability.Methods  In a prospective study, 72 patients were assessed before PUVA therapy and again when they had achieved clearance of their psoriasis.Results  Patients demonstrated significant reductions in psoriasis-related disability, psoriasis-related stress or daily hassles and in the frequency of psoriasis-related symptoms. By comparison, there were no significant differences in levels of anxiety, depression or worrying. Similarly, patients' perceptions about cure, potential chronicity, causes, consequences and coping also remained unchanged.Conclusions  These results suggest that while clearance of psoriasis produces a significant reduction in factors specific to psoriasis (disability and stress), it does not impact upon psychological distress, on patients' beliefs about psoriasis or on coping. This observation highlights the complex features of patients' psychological experience of psoriasis and may provide further impetus for integration of psychological interventions into standard care protocols.

Notes: Summary Background Psoriasis is an immunologically mediated, probably autoimmune, disease in which T-helper type 1 cytokines play an important role. Established autoimmune diseases, with similar mechanistic characteristics to psoriasis, include multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus and systemic lupus erythematosus. Natural killer (NK) and natural killer-T (NK-T) cells are considered key to the pathogenesis of these conditions, which are characterized by reduced numbers of NK cells in peripheral blood. NK and NK-T cells have been implicated in the pathogenesis of psoriasis and are present in plaques of psoriasis. Objectives To investigate whether levels of NK and NK-T cells are reduced in the peripheral blood of patients with psoriasis. Methods Fourteen patients with untreated psoriasis, mean ± SD age 46 ± 13 years, and 13 healthy volunteers, mean ± SD age 34 ± 9 years, were venesected and peripheral blood mononuclear cells isolated, labelled with a panel of antibodies to T-cells and NK cells including CD3, CD56, CD57, CD16, CD94, CD158a, CD69 and cutaneous lymphocyte-associated antigen (CLA) and analysed using triple-colour flow cytometry. Results There were significantly fewer cells expressing the NK-cell markers CD16 (P 〈 0·001), CD56 (P 〈 0·003), CD94 (P 〈 0·001) and CD158a (P 〈 0·02) in patients with psoriasis compared with normal controls. However, circulating numbers of NK-T cells (CD3+ CD56+ CD57+), T-cells (CD3+), activated lymphocytes (CD69+) or CLA+ cells were not significantly different between patients with psoriasis and controls. Conclusions Circulating NK cells are reduced in psoriasis. This finding is similar to those in established autoimmune diseases such as rheumatoid arthritis. This observation provides some evidence that psoriasis may be an autoimmune disease in which NK cells play a role.

Notes: Abstract: A C-insertion polymorphism in the NOD2 gene (3020insC) on chromosome 16 is a rare mutation associated with Crohn's disease. Crohn's disease and psoriasis are more commonly observed together than expected by chance. Furthermore a susceptibility locus for psoriasis has been identified on chromosome 16q which overlaps the recently identified susceptibility locus for Crohn's disease. Thus, NOD2 may potentially be important as a candidate susceptibility gene for psoriasis. We tested this hypothesis by genotyping psoriasis patients for the C-insertion polymorphism using the Taqman ABI 7700 sequencing system. No statistically significant differences were observed between psoriasis vulgaris (n = 216), palmo-plantar pustular psoriasis (PPP) (n = 100), guttate psoriasis (n = 118) and the control group (n = 283). In both patient and control groups, no mutant homozygotes were observed and approximately 4% were heterozygotes. This particular insertion mutation in the NOD2 gene does not appear to contribute to the genetic susceptibility of psoriasis vulgaris, PPP or guttate psoriasis. However, other mutations exist in the NOD2 gene, which may potentially have a role in psoriasis susceptibility.