Annice Heratizadeh

Malassezia sympodialis thioredoxin–specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis

BACKGROUND IgE-mediated cross-reactivity between fungal antigens and human proteins has been described in patients with atopic dermatitis (AD), but it remains to be elucidated whether there is also cross-reactivity at the T-cell level. OBJECTIVE We sought to explore cross-reactivity at the T-cell level between the fungal thioredoxin (Mala s 13) of the skin-colonizing yeast Malassezia sympodialis and its homologous human thioredoxin (hTrx). METHODS T-cell lines (TCLs) were generated in the presence of rMala s 13 from the peripheral blood and from skin biopsy specimens of positive patch test reactions of patients with AD sensitized to Mala s 13 and hTrx. Patients with AD not sensitized to Malassezia species, healthy subjects, and patients with psoriasis served as control subjects. Mala s 13-specific T-cell clones (TCCs) were generated from TCLs. TCCs were characterized by antigen specificity, phenotype, and cytokine secretion pattern. Human keratinocytes were stimulated with IFN-γ, TNF-α, and IL-4, and the release of hTrx was determined by means of ELISA. RESULTS Mala s 13-specific TCLs and TCCs from the blood and skin of patients with AD sensitized to Mala s 13 and hTrx were fully cross-reactive with hTrx. Mala s 13- and hTrx-specific TCCs could not be generated from control subjects. The majority of cross-reactive TCCs were CD4(+) and coexpressed cutaneous lymphocyte antigen. In addition to T(H)1 and T(H)2 TCCs, we could also identify TCCs secreting IL-17 and IL-22. After stimulation with IFN-γ and TNF-α, keratinocytes released substantial amounts of thioredoxin. CONCLUSION In patients with AD sensitized to Malassezia species, cross-reactivity at the T-cell level to Mala s 13 and the homologous hTrx is detectable. hTrx autoreactive skin-homing T cells might be relevant for cutaneous inflammation in patients with AD.

Neurodermitis S2-Leitlinie

© Dt. Dermatologische Gesellschaft u. a. • Journal compilation

Isolation of α-toxin-producing Staphylococcus aureus from the skin of highly sensitized adult patients with severe atopic dermatitis.

Background  Staphylococcus aureus (S. aureus) is a well‐known trigger factor of atopic dermatitis (AD). Besides staphylococcal superantigens, α‐toxin may influence cutaneous inflammation via induction of T‐cell proliferation and cytokine secretion.

S2k-Leitlinie Neurodermitis [atopisches Ekzem; atopische Dermatitis] – Kurzversion

Bei dem Krankheitsbild der Neurodermitis handelt es sich um eine chronische oder chronisch‐rezidivierende, nichtkontagiöse, entzündliche Hauterkrankung mit in der Regel starkem Juckreiz. Darüber hinaus besteht ein Risiko für komplizierte Verläufe mit bakteriellen oder viralen Superinfektionen. Sowohl die genetische Prädisposition als auch zahlreiche Auslösefaktoren spielen für die Erstmanifestation und das Auftreten der Erkrankungsschübe eine wichtige Rolle, so dass auch die Therapiekonzepte vielfältig sind. Bei zahlreichen für die Neurodermitis zur Verfügung stehenden Behandlungsoptionen gilt es, in Abstimmung mit den Patienten bzw. Eltern erkrankter Kinder fallorientiert einen optimalen Behandlungsplan aufzustellen, der im Verlauf ggf. erneut angepasst werden muss.

The role of T‐cell reactivity towards the autoantigen α‐NAC in atopic dermatitis

Background  A subgroup of patients with atopic dermatitis (AD) produces IgE autoantibodies to human proteins which may be present in inflamed skin and perpetuate cutaneous inflammation.

S2k guideline on diagnosis and treatment of atopic dermatitis — short version

SummaryAtopic dermatitis (AD) represents a pruritic, non-contagious, chronic or chronically relapsing, inflammatory skin disease. The course of the disease may be complicated by bacterial or viral superinfections. The first manifestation of the disease and further flare-ups are due to genetic predisposition and also to a variety of further trigger factors. The therapy regimen should be adapted to disease symptoms that are actually present and consider individual features of the disease as reported by the patients or their parents. This short version of the German guideline on AD provides an overview of evidence-based diagnostic and treatment options. All recommendations made here are the result of a consensus of the scientific medical societies, working groups and support groups based on scientific data published to date. Abstracts and details of the studies cited are provided in the long version of this guideline (see: www.awmf.org).

Impaired NLRP3 inflammasome expression and function in atopic dermatitis due to Th2 milieu

Atopic dermatitis (AD) and psoriasis patients are frequently colonized with Staphylococcus aureus (S. aureus) that produce the staphylococcal exotoxin α‐toxin. However, only patients with AD suffer from bacterial superinfections with this pathogen, which implicates immunological differences in AD vs psoriasis in combating these bacteria. S. aureus recognition is partially mediated by intracellular nucleotide‐binding oligomerization domain receptors (NLRs), which link α‐toxin to caspase‐1 activation through the formation of the NLRP3 inflammasome and to IL‐1β secretion.

Immunoglobulin E antibody reactivity to bacterial antigens in atopic dermatitis patients

Cite this as: K. Reginald, K. Westritschnig, T. Werfel, A. Heratizadeh, N. Novak, M. Focke‐Tejkl, A. M. Hirschl, D. Y. M. Leung, O. Elisyutina, E. Fedenko and R. Valenta, Clinical & Experimental Allergy, 2011 (41) 357–369.

Cytokine Effects Induced by the Human Autoallergen α-NAC

Autoallergy is a phenomenon found in a subgroup of patients with atopic dermatitis (AD). These patients exhibit serum IgE reactivity toward autoantigens like the alpha-chain of the nascent polypeptide-associated complex (α-NAC; Hom s 2). α-NAC has been shown before to induce T-cell proliferation and secretion of IFN-γ. To elucidate the immune modulating functions α-NAC may exert, we analyzed its effects on cytokine transcription and secretion in peripheral blood mononuclear cells (PBMCs), monocytes, and CD4+ T cells. Transcription and secretion of IFN-γ, IL-17, and IL-22 were increased in α-NAC-stimulated PBMCs. As IL-17 was significantly upregulated by α-NAC, we assessed signal transduction in PBMCs and found signal transducer and activator of transcription 3 phosphorylation in α-NAC-stimulated cells. Furthermore, we could show the importance of monocyte activation by α-NAC, as isolated T cells reacted only weakly toward the stimulation. Inhibition of IL-23 p19 led to lower amounts of IL-17 in the PBMC supernatants after α-NAC stimulation. α-NAC stimulation of PBMCs from non-allergic donors resulted in secretion of IL-10, which was greatly reduced in PBMCs from α-NAC-sensitized AD patients. Our findings provide insights into the mechanisms of autoallergy, investigating the interplay of immune cells, signaling events, and cytokines, which are known to be relevant in atopic skin inflammation.

Staphylococcal α-toxin induces a higher T cell proliferation and interleukin-31 in atopic dermatitis.

Background: Patients with atopic dermatitis (AD) are frequently colonized with α-toxin-producing Staphylococcus aureus which is in turn positively correlated with the severity of eczema. Methods: In this study we addressed T cell proliferation and T cell as well as monocyte cytokine secretion upon α-toxin stimulation in peripheral blood mononuclear cells (PBMCs) from AD patients compared to healthy controls. Results: We found that α-toxin stimulation of PBMCs markedly enhanced T cell proliferation both in patients with AD and healthy controls and was significantly increased in AD patients compared to healthy controls. PBMCs of AD patients secreted significantly more IL-31 compared to those of healthy controls upon α-toxin and SEB stimulation. Moreover, α-toxin stimulation yielded an increase in T cell (IL-2, IL-9, IL-10 and IFN-γ) as well as monocyte (IL-1β and TNF-α) cytokine secretion. Conclusion: Our results could partly explain how skin colonization and infection with S. aureus can contribute to chronic skin inflammation and pruritus in AD.