| 1. |
- Johansson, Catharina, et al.
(författare)
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Elevated Peripheral Allergen-Specific T Cell Response Is Crucial for a Positive Atopy Patch Test Reaction
- 2009
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 150:1, s. 51-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Atopic eczema is a chronic inflammatory skin disease in which several subgroups of cases can be identified. Atopy patch testing (APT) reveals allergen sensitization also in atopic eczema patients devoid of detectable allergen-specific IgE, suggesting the importance of factors other than IgE in the reaction. Here we investigate the relationship between APT reactions and allergen-specific peripheral IgE and T cell reactivity in atopic eczema patients. Methods: Adult patients with atopic eczema (n = 64) and healthy controls (n = 24) were analyzed for reactivity to Malassezia sympodialis extract by APT, measurement of specific plasma IgE and in vitro determination of the frequency of allergen-reactive peripheral blood mononuclear cells producing interleukin-4 and interleukin-5 using the ELISpot method. Results: When combining the results of the APT, IgE measurements and the ELISpot analyses, reactivity to M. sympodialis was found in a majority of the atopic eczema patients (69%), whereas the healthy controls were negative throughout. T cell reactivity to M. sympodialis, manifested by production of both interleukins 4 and 5, was highly predictive for a positive APT reaction and displayed a strongly positive correlation with the APT score. In contrast, the allergen-specific IgE levels did not predict the APT outcome, and no correlation could be found between the IgE levels and the APT score. Conclusion: Peripheral allergen-specific T helper 2 cell-mediated reactivity appears to be required for a positive APT reaction to M. sympodialis. The diagnostic potential of measuring peripheral allergen-specific T cell responses should be considered in atopic eczema.
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| 2. |
- Sääf, Annika, et al.
(författare)
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Characterization of EGFR and ErbB2 expression in atopic dermatitis patients.
- 2012
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Ingår i: Archives of Dermatological Research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 304:10, s. 773-80
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Tidskriftsartikel (refereegranskat)abstract
- Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases in industrialized countries. To identify candidate genes involved in the pathogenesis of AD, we previously undertook a genome-wide approach using DNA microarrays. A transcript encoding the epidermal growth factor receptor (EGFR) was found to be among the down-regulated transcripts in AD skin. Here, we further investigated the expression pattern of two EGFR family members (EGFR and ErbB2) in AD skin on a protein level. Immunohistochemical (IHC) analysis of EGFR and ErbB2 showed decreased expression of EGFR and ErbB2 proteins in AD lesional skin as compared to skin from healthy individuals. Interestingly, we found that EGFR and ErbB2 were reciprocally expressed in an in vitro model of keratinocyte proliferation and differentiation, paralleling the expression patterns found in epidermis of healthy skin. The highest levels of EGFR transcripts were found in proliferating cells, while ErbB2 was found in differentiated cells. We show that blocking EGFR activity combined with co-stimulation of the Th2-cytokine IL4 in keratinocytes leads to induction of the inflammatory chemokine CCL26/eotaxin-3 in vitro. Accordingly, increased CCL26 transcriptional levels were observed in AD lesional skin. Taken together, suppression of EGFR may contribute to the pathogenesis of AD via the regulation of inflammatory chemokines.
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| 3. |
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| 4. |
- Sonkoly, Enikö, et al.
(författare)
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MicroRNAs : novel regulators involved in the pathogenesis of psoriasis?
- 2007
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 2:7
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Tengvall Linder, Maria
(författare)
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Immunological mechanisms in atopic dermatitis : clinical and experimental studies
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the study was to investigate immunological mechanisms in atopic dermatitis. Serum IgE levels are elevated in 80% of atopic dermatitis patients and CD4+ T cells and environmental allergens are known to be of importance in the pathogenesis of the disease. It was therefore of interest to further elucidate the role of these factors in atopic dermatitis. Cyclosporin A (CSA) was used as a tool for exploring the pathogenesis of atopic dermatitis, with emphasis on the expression of IgE, the low-affinity IgE receptor (CD23), intercellular adhesion molecule-1 (ICAM-1) and eosinophils in a placebo-controlled study of ten patients with persistent atopic dermatitis. CSA reduced the expression of epidermal and dermal IgE and CD23, ICAM-1 on keratinocytes, and the number of eosinophils in lesional skin. The effects are most likely due to a decrease in the amounts of T cell derived cytokines in the skin. The inflammatory and pruritogenic properties of interleukin-2 (IL-2) were explored by a single intradermal injection of IL-2 into eight atopic dermatitis patients and eight healthy individuals in a placebo-controlled study. IL-2 induced local itch, erythema, dermal infiltration of CD4+ T cells, spongiosis, exocytosis and activation of keratinocytes in atopic dermatitis patients, indicating that IL-2 may be of importance in skin inflammation in atopic dermatitis. The yeast Pityrosporum orbiculare, a member of the normal microflora of human skin, is considered to be one of the factors contributing to atopic dermatitis. Serum lgE antibodies or positive skin prick tests to P. orbiculare are found with a frequency of 14-71% in patients with atopic dermatitis, but rarely in atopic respiratory diseases without atopic dermatitis or in healthy controls. The proliferative response of peripheral blood mononuclear cells (PBMC) to P. orbiculare extract was investigated in ten patients with atopic dermatitis and six healthy individuals and was found to be significantly higher in the atopic dermatitis patients. From two atopic dermatitis patients, T-cell clones (TCCs) from skin and blood were established and characterized. The investigated TCCs were CD4+ and a majority of the skin derived T cells showed a Th2 or Th2/ThO-like cytokine profile. In addition, cytokine production was investigated in blood-derived P. orbiculare-stimulated T-cell lines (TCLs) from eleven atopic dermatitis patients and six healthy individuals. The TCLs derived from atopic dermatitis patients produced significantly higher levels of Th2 cytokines than those from the healthy individuals. Fifteen atopic dermatitis patients, eight seborrhoeic dermatitis patients and eight healthy individuals were patch tested with P. orbiculare extract on tape-stripped non-lesional skin. The seborrhoeic dermatitis patients and the healthy individuals were RAST and patch test negative for P. orbiculare. Thirteen out of fifteen atopic dermatitis patients had serum IgE antibodies to P. orbiculare and eight of them showed a positive patch test reaction to P. orbiculare, with a maximal intensity at 48 h. Significantly higher serum levels of P. orbiculare specific lgE were detected in patch test positive compared to the negative atopic dermatitis patients indicating that allergen-specific IgE is important for initiating an allergen-specific eczematous response. In the atopic dermatitis patients, an infiltration of CD4+ T cells and eosinophils was present at the P. orbiculare positive patch test sites along with an up-regulation of ICAM-1 and HLA-DR expression. The Th2-like cytokine profile of P. orbiculare reactive TCCs and TCLs together with the positive patch test response to R orbiculare in sensitized atopic dermatitis patients indicate that P. orbiculare may be of importance for triggering and maintaining IgE mediated skin inflammation in these patients. Patch tests with P. orbiculare extract may serve as a diagnostic tool in a subgroup of atopic dermatitis patients.
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