Maritza A. Middelkamp-Hup

Increased frequencies of IL‐31‐producing T cells are found in chronic atopic dermatitis skin

Abstract:  Interleukin (IL)‐31 has been associated with pruritus, a characteristic feature of atopic dermatitis (AD). Local T cell responses may be responsible for the increased level of IL‐31 mRNA observed in AD. We investigated the frequency of IL‐31‐producing T cells in AD lesions, as well as their cytokine profile. T cells were isolated from chronic AD lesions, autologous blood and healthy donor skin. Intracellular expression of IL‐31, IFN‐γ, IL‐13, IL‐17 and IL‐22 was measured using flow cytometry. T cells from AD lesions contained significantly higher percentages of IL‐31‐producing T cells compared to autologous blood and donor skin. Many IL‐31‐producing T cells co‐produced IL‐13 and to lesser extent IL‐22, but rarely IFN‐γ or IL‐17. A substantial part of the IL‐31‐producing T cells did not co‐produce any of the other cytokines and could therefore not be linked to any of the known functionally different T cell subsets. The T cell infiltrates were also relatively enriched for Th2/Tc2 and Th22/Tc22 cells, while frequencies of Th1/Tc1 and Th17 cells were decreased. This is the first report describing the detection of IL‐31 at protein level in skin‐infiltrating T cells. We show here that T cells in chronic AD skin produce IL‐31 and that AD lesions contain increased levels of these IL‐31‐producing T cells. This suggests that a substantial part of previously reported increased IL‐31 mRNA levels in AD skin is T cell derived and that these cells may be involved in the pathogenesis of AD.

Skin barrier in atopic dermatitis

The skin represents the largest organ of the body and provides a vital interface between the body and the environment. Hereditary and acquired alterations of structural proteins and lipids of the stratum corneum and epidermal tight junctions leading to a diminished skin barrier function are major causative factors for a number of skin diseases, in particular atopic dermatitis (AD). This review summarizes current knowledge on the role of the skin barrier in AD with regard to pathogenesis and treatment, on the relationship between skin barrier abnormalities and immune aberrations, and on potential therapies aimed at repair of the skin barrier. Furthermore recent advances in the genetics of AD will be addressed.

The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey.

There is a paucity of evidence for the use of systemic agents in children with atopic eczema refractory to conventional therapy, resulting in considerable variation in patient management.

Atopic eczema or atopiform dermatitis

Please cite this paper as: Atopic eczema or atopiform dermatitis. Experimental Dermatology 2010.

Cytokine profiles in interstitial fluid from chronic atopic dermatitis skin

The in vivo levels of inflammatory mediators in chronic atopic dermatitis (AD) skin are not well‐defined due to the lack of a non‐invasive or minimally invasive sampling technique.

Contact sensitization in Dutch children and adolescents with and without atopic dermatitis – a retrospective analysis

Allergic contact dermatitis is known to occur in children with and without atopic dermatitis, but more data are needed on contact sensitization profiles in these two groups.

TREatment of ATopic eczema (TREAT) Registry Taskforce: Protocol for an international Delphi exercise to identify a core set of domains and domain items for national atopic eczema registries

BackgroundPatients with moderate-to-severe atopic eczema (AE) often require photo- or systemic immunomodulatory therapies to induce disease remission and maintain long-term control. The current evidence to guide clinical management is small, despite the frequent and often off-label use of these treatments. Registries of patients on photo- and systemic immunomodulatory therapies could fill this gap, and the collection of a core set concerning these therapies in AE will allow direct comparisons across registries as well as data sharing and pooling.Using an eDelphi approach, the international TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek consensus between key stakeholders internationally on a core set of domains and domain items for AE patient registries with a research focus that collect data of children and adults on photo- and systemic immunomodulatory therapies.Methods/designParticipants from six stakeholder groups will be invited: doctors, nurses, non-clinical researchers, patients, as well as industry and regulatory body representatives. The eDelphi will comprise three sequential online rounds, requesting participants to rate the importance of each proposed domain and domain items. Participants will be able to add domains and domain items to the proposed list in round 1. A final consensus meeting will be held with representatives of each stakeholder group.DiscussionIdentifying a uniform core set of domains and domain items to be captured by AE patient registries will increase the utility of individual registries, and provide greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immunomodulatory therapies to guide clinical management across dermatology centres and country borders.Trial registrationNot applicable. This eDelphi study was registered in the Core Outcome Measures for Effectiveness Trials (COMET) database.

House Dust Mite allergens Der f and Der p induce IL‐31 production by blood derived T cells from Atopic Dermatitis patients

Aero‐allergens, such as house dust mite (HDM), have been suggested to play a role in the initiation of atopic dermatitis (AD)‐related skin inflammation. Here, we analysed the proliferation and the cytokine expression of blood‐derived T cells from AD and healthy individuals upon HDM‐allergen stimulation. The proliferating cells from healthy individuals and AD patients had a significantly different, distinct cytokine profile: in AD blood, we found increased frequencies of HDM‐reactive IL‐31‐producing T cells, as well as a decreased Th1/Th2 and Tc1/Tc2 ratio, suggesting that allergen‐specific T cells in blood of chronic AD patients are subject to pre‐existent Th2‐Tc2 and “Th31‐Tc31” programming.

TREatment of ATopic eczema (TREAT) Registry Taskforce: an international Delphi exercise to identify a core set of domains and domain items for national atopic eczema photo- and systemic therapy registries

Evidence of immunomodulatory therapies to guide clinical management of atopic eczema (AE) is scarce, despite frequent and often off‐label use. Patient registries provide valuable evidence for the effects of treatments under real‐world conditions that can inform treatment guidelines, give the opportunity for health economic evaluation and the evaluation of quality of care, as well as pharmacogenetic and dynamic research, which cannot be adequately addressed in clinical trials.