MicroRNAs: Novel Regulators Involved in the Pathogenesis of Psoriasis?

MicroRNAs are a recently discovered class of posttranscriptional regulators of gene expression with critical functions in health and disease. Psoriasis is the most prevalent chronic inflammatory skin disease in adults, with a substantial negative impact on the patients' quality of life. Here we show for the first time that psoriasis-affected skin has a specific microRNA expression profile when compared with healthy human skin or with another chronic inflammatory skin disease, atopic eczema. Among the psoriasis-specific microRNAs, we identified leukocyte-derived microRNAs and one keratinocyte-derived microRNA, miR-203. In a panel of 21 different human organs and tissues, miR-203 showed a highly skin-specific expression profile. Among the cellular constituents of the skin, it was exclusively expressed by keratinocytes. The up-regulation of miR-203 in psoriatic plaques was concurrent with the down-regulation of an evolutionary conserved target of miR-203, suppressor of cytokine signaling 3 (SOCS-3), which is involved in inflammatory responses and keratinocyte functions. Our results suggest that microRNA deregulation is involved in the pathogenesis of psoriasis and contributes to the dysfunction of the cross talk between resident and infiltrating cells. Taken together, a new layer of regulatory mechanisms is involved in the pathogenesis of chronic inflammatory skin diseases

The Expression of BAFF, APRIL and TWEAK Is Altered in Eczema Skin but Not in the Circulation of Atopic and Seborrheic Eczema Patients

The TNF family cytokines BAFF (B-cell activating factor of the TNF family) and APRIL (a proliferation-inducing ligand) are crucial survival factors for B-cell development and activation. B-cell directed treatments have been shown to improve atopic eczema (AE), suggesting the involvement of these cytokines in the pathogenesis of AE. We therefore analyzed the expression of these TNF cytokines in AE, seborrheic eczema (SE) and healthy controls (HC). The serum/plasma concentration of BAFF, APRIL and a close TNF member TWEAK (TNF-like weak inducer of apoptosis) was measured by ELISA. The expression of these cytokines and their receptors in skin was analyzed by quantitative RT-PCR and immunofluorescence. Unlike other inflammatory diseases including autoimmune diseases and asthma, the circulating levels of BAFF, APRIL and TWEAK were not elevated in AE or SE patients compared with HCs and did not correlate with the disease severity or systemic IgE levels in AE patients. Interestingly, we found that the expression of these cytokines and their receptors was altered in positive atopy patch test reactions in AE patients (APT-AE) and in lesional skin of AE and SE patients. The expression of APRIL was decreased and the expression of BAFF was increased in eczema skin of AE and SE, which could contribute to a reduced negative regulatory input on B-cells. This was found to be more pronounced in APT-AE, the initiating acute stage of AE, which may result in dysregulation of over-activated B-cells. Furthermore, the expression levels of TWEAK and its receptor positively correlated to each other in SE lesions, but inversely correlated in AE lesions. These results shed light on potential pathogenic roles of these TNF factors in AE and SE, and pinpoint a potential of tailored treatments towards these factors in AE and SE

Differences in cutaneous melanoma treatment and patient satisfaction.

Although clinical guidelines exist, the management of patients with cutaneous melanoma (CM) is a complex process that may vary between different care providers with potential dysfunctions ultimately mirrored in the overall patient satisfaction. The aim of the present study was to investigate the CM management as related to lead times, surgical quality and diagnosis communication with the hypothesis that the care may differ between providers and disparities may impact patient satisfaction. Medical records of 181 patients were retrospectively analyzed with parallel patient satisfaction evaluation by telephone interviews. Overall mean lead times from initial diagnosis until completion of all surgery and histopathology reports were 80-100 days and delays occurred at every step of the process. General practitioners performed excision biopsies faster however this was mitigated by slower histopathology processing. University level CM care showed less lag time between excision biopsy, wide local excision for thick melanomas and histopathology confirmation. University level care operated with twice the surgical margin as compared to general practitioners and non-university level specialists. Male patients had larger excision biopsy margins and significantly shorter lead times than female patients. Patient satisfaction rates were generally higher in the academic hospitals as compared to general practitioners and non-university dermatology clinics. Surprisingly, there was no correlation between lead times and patient satisfaction. Taken together, CM show substantial variation and caution should be practiced when using patient satisfaction as a quality indicator

IgE sensitization profiles differ between adult patients with severe and moderate atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a complex chronic inflammatory disease where allergens can act as specific triggering factors. AIM: To characterize the specificities of IgE-reactivity in patients with AD to a broad panel of exogenous allergens including microbial and human antigens. METHODOLOGY: Adult patients with AD were grouped according to the SCORAD index, into severe (n = 53) and moderate AD (n = 126). As controls 43 patients were included with seborrhoeic eczema and 97 individuals without history of allergy or skin diseases. Specific IgE reactivity was assessed in plasma using Phadiatop®, ImmunoCap™, micro-arrayed allergens, dot-blotted recombinant Malassezia sympodialis allergens, and immune-blotted microbial and human proteins. RESULTS: IgE reactivity was detected in 92% of patients with severe and 83% of patients with moderate AD. Sensitization to cat allergens occurred most frequently, followed by sensitization to birch pollen, grass pollen, and to the skin commensal yeast M. sympodialis. Patients with severe AD showed a significantly higher frequency of IgE reactivity to allergens like cat (rFel d 1) and house dust mite (rDer p 4 and 10), to Staphylococcus aureus, M. sympodialis, and to human antigens. In contrast, there were no significant differences in the frequencies of IgE reactivity to the grass pollen allergens rPhl p 1, 2, 5b, and 6 between the two AD groups. Furthermore the IgE reactivity profile of patients with severe AD was more spread towards several different allergen molecules as compared to patients with moderate AD. CONCLUSION: We have revealed a hitherto unknown difference regarding the molecular sensitization profile in patients with severe and moderate AD. Molecular profiling towards allergen components may provide a basis for future investigations aiming to explore the environmental, genetic and epigenetic factors which could be responsible for the different appearance and severity of disease phenotypes in AD

Frequencies of allergen-specific IgE reactivities in the AD and SE patients as tested by MeDALL allergen chip, Immunoblotting, ImmunoCAP^™ and RAST-based dot-blot assay.

<p>Frequencies of allergen-specific IgE reactivities in the AD and SE patients as tested by MeDALL allergen chip, Immunoblotting, ImmunoCAP^™ and RAST-based dot-blot assay.</p

Summary of allergen-specific IgE reactivities in the AD patients.

<p>Summary of allergen-specific IgE reactivities in the AD patients.</p

Pie charts showing the contribution of (A), allergen sources and (B), individual allergen components to IgE sensitization.

<p>Each chart represents 100% of IgE reactivities detected in plasma from all AD patients of the respective group, severe AD (left chart) and moderate AD (right chart), in (<b>A)</b> to six allergen sources using the MeDALL allergen-chip (ISU ≥ 0.3) and to extracts of <i>M</i>. <i>sympodialis</i>, <i>S</i>. <i>aureus</i> and the human cell line A431 using immunoblotting, and in (<b>B)</b> to 25 allergen molecules using the MeDALL allergen-chip (ISU ≥ 0.3). The sizes of the segments represent the proportion of the respective in (<b>A)</b>, allergen source and in (<b>B)</b>, allergen molecule among all recognized. Allergen sources/molecules start a 12 o’clock of the pie chart and continue clock-wise as listed with the color code.</p