Institutionen för laboratoriemedicin / Department of Laboratory Medicine
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