This study demonstrates that controlled exposure to airborne allergens of patients with a so-called extrinsic IgE-mediated form of AD induced a worsening of cutaneous symptoms.
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Regulatory T cells (Tregs) are known to play critical roles in homeostasis and immune responses in the skin. Whether Treg frequencies are altered in atopic dermatitis (AD) patients has been addressed by several studies, leading to conflicting results. The detection of Tregs by FOXP3 expression may lead to false-positive results as activated T cells without regulatory function may transiently upregulate this transcription factor. In contrast, measurement of the DNA methylation status of a region within the FOXP3 locus that is selectively demethylated only in bona fide Tregs (Treg-specific demethylated region, TSDR) represents a reliable method to quantify Tregs. Here, we measured circulating Treg frequencies of adult patients and detected a positive correlation with disease severity. Subsequent surface marker analysis revealed higher frequencies of CD45RA(+) CCR7(-) tissue-homing Tregs in the patient group with a tendency of reduced expression of CD39 compared with healthy donors, a marker for the highly suppressive TREM subtype.
Atopic dermatitis (AD), one of the most frequent inflammatory skin diseases worldwide, is believed to result from a disturbed skin barrier as well as aberrant immune reactions against per se harmless allergens. Starting mostly during childhood with a chronic, remitting relapsing course, the disease can persist into adulthood in about one fifth of patients. Immune reactions to self-proteins have been observed in AD patients already in the beginning of the Twentieth century, when human cellular extracts were shown to provoke skin lesions. However, the term “autoimmunity” has never been claimed, since AD is first and foremost an atopic disease. In contrast, this IgE-hallmarked autoreactivity was termed “autoallergy” and is ongoing discussed regarding its impact on the disease. Since severely affected patients tend to develop IgE-hypersensitivity reactions to numerous environmental allergens, the impact of immune responses to self-proteins is difficult to determine. On the other hand: any autoreactivity, irrespective of the magnitude, implicates the potential of driving the chronification of the disease while shaping the immune response. This review article revisits the observations made on autoallergy from an actual point of view and tries to approach the question whether these still point to a contribution to the disease.
Autoreactivity may play a critical role in the chronification of atopic dermatitis (AD). Several studies showed that AD patients produce IgE Abs specific for autoantigens, and we described Th as well as CD8+ T cells specific for the autoallergen Hom s 2, the α-chain of the nascent polypeptide-associated complex (α-NAC). This study aimed to investigate the frequency and inflammatory phenotype of autoallergen-specific CD8+ T cells. CD8+ T cell immunodominant epitopes of α-NAC were mapped by applying prediction softwares, and binding affinity was confirmed by stabilization of empty MHC complexes. MHC class I tetramers were assembled and binding cells were analyzed directly ex vivo by flow cytometry and in terms of single-cell assessment by ChipCytometry. We report significantly elevated numbers of α-NAC–specific peripheral T cells in sensitized patients compared with nonatopic controls. These cells secrete IL-4 and IFN-γ, and surface markers revealed significantly elevated frequencies of circulating terminally differentiated α-NAC–specific CD8+ T cells in patients with AD compared with nonatopic donors. The observed phenotype of α-NAC–specific CD8+ T cells indicates a role in the pathogenesis of AD.
International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079-88 Haralambieva E, Kleiverda K, Mason DY et al. (2002) Detection of three common translocation breakpoints in non-hodgkin's lymphomas by fluorescence in situ hybridization on routine paraffin-embedded tissue section.
Atopic dermatitis (AD) is a chronic inflammatory skin disease, which is characteristically associated with intense pruritus and eczematous lesions. 1 Robert Willan, an English dermatologist, was the first to describe the disease in 1808. 2 In most countries, over 20% of children are affected at least once during a period of their lives. [3][4][5] Despite the fact that 85% of all cases manifest before the age of five, AD can occur lifelong and the prevalence of AD is still high in adulthood. 6-8 Surprisingly, recent data based on two birth cohorts revealed that only 38% of adult AD patients in the United Kingdom reported a childhood onset of symptoms. 9Patients suffering from AD are prone to viral and bacterial infections. 5 Staphylococcus aureus (S. aureus) infections are particularly common in AD patients, leading to superinfection. 10
Biomay AG Vienna funded this work. Disclosure of potential conflict of interest: P. Colombo's institute received BIOMAY AG for this work and his institute received patents from the Italian National Research Council for other work. A. Bonura's institute received patents from the Italian National Research Council for other work. The rest of the authors declare that they have no relevant conflicts of interest. 1022-34. 2. Valenta R, Campana R, Focke-Tejkl M, Niederberger V. Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: lessons from the past and novel mechanisms of action for the future.
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