Immunological mechanisms in atopic dermatitis : clinical and experimental studies

Detta är en avhandling från Stockholm : Karolinska Institutet, Department of Laboratory Medicine

Sammanfattning: 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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