Immunotopographical Differences of Human Skin

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Investigation of Skin Barrier Functions and Allergic Sensitization in Patients with Hyper-IgE Syndrome

Purpose Hyper-IgE syndrome (HIES) is a severe primary immunodeficiency, characterized by increased serum IgE levels as well as recurrent infections and atopic dermatitis (AD)-like skin lesions. AD is a chronic inflammatory skin disease with immunologic alterations (Th2-Th22 polarization) and characteristic skin barrier dysfunctions. Our aim was to investigate physicochemical skin barrier alterations and allergic sensitization in STAT3-HIES patients in order to explore whether skin barrier dysfunction can play a role in the eczematoid skin lesions in these patients. Methods In our experiments STAT3 and FLG mutation analyses were performed in STAT3-HIES (n=7) and AD (n=49) patients. Laboratory parameters (LDH and Eos counts), immunologic alterations (Th17 cell counts), allergic sensitization (total and specific IgE levels, skin prick tests, and medical history records), skin barrier changes [transepidermal water loss (TEWL), skin pH], serum and stratum corneum thymic stromal lymphopoietin (TSLP) levels were also examined. Results Impaired Th17 cell numbers, but normal physicochemical barrier functions, as well as serum and stratum corneum TSLP levels, were found in STAT3-HIES, while these parameters were significantly altered in AD patients. Allergic sensitization was detected in nearly all AD patients, while no signs of sensitization occurred in STAT3-HIES. Conclusions Our study demonstrated that the skin barrier functions of STAT3-HIES patients are not damaged and they differ significantly from the altered skin barrier functions of AD patients. Awell-functioning physicochemical skin barrier may be one of the explanations on the contradiction between the extremely high total IgE levels and the lack of allergic sensitization in these patients. Our study underlines the importance of skin barrier in the development of allergic sensitization

Investigation of Skin Barrier Functions and Allergic Sensitization in Patients with Hyper-IgE Syndrome

Purpose Hyper-IgE syndrome (HIES) is a severe primary immunodeficiency, characterized by increased serum IgE levels as well as recurrent infections and atopic dermatitis (AD)-like skin lesions. AD is a chronic inflammatory skin disease with immunologic alterations (Th2-Th22 polarization) and characteristic skin barrier dysfunctions. Our aim was to investigate physicochemical skin barrier alterations and allergic sensitization in STAT3-HIES patients in order to explore whether skin barrier dysfunction can play a role in the eczematoid skin lesions in these patients. Methods In our experiments STAT3 and FLG mutation analyses were performed in STAT3-HIES (n=7) and AD (n=49) patients. Laboratory parameters (LDH and Eos counts), immunologic alterations (Th17 cell counts), allergic sensitization (total and specific IgE levels, skin prick tests, and medical history records), skin barrier changes [transepidermal water loss (TEWL), skin pH], serum and stratum corneum thymic stromal lymphopoietin (TSLP) levels were also examined. Results Impaired Th17 cell numbers, but normal physicochemical barrier functions, as well as serum and stratum corneum TSLP levels, were found in STAT3-HIES, while these parameters were significantly altered in AD patients. Allergic sensitization was detected in nearly all AD patients, while no signs of sensitization occurred in STAT3-HIES. Conclusions Our study demonstrated that the skin barrier functions of STAT3-HIES patients are not damaged and they differ significantly from the altered skin barrier functions of AD patients. Awell-functioning physicochemical skin barrier may be one of the explanations on the contradiction between the extremely high total IgE levels and the lack of allergic sensitization in these patients. Our study underlines the importance of skin barrier in the development of allergic sensitization

Sebaceous gland rich skin is characterized by TSLP expression and distinct immune surveillance which is disturbed in rosacea

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Rosacea Is Characterized by a Profoundly Diminished Skin Barrier

Rosacea is a common chronic inflammation of sebaceous glanderich facial skin characterized by severe skin dryness, elevated pH, transepidermal water loss, and decreased hydration levels. Until now, there has been no thorough molecular analysis of permeability barrier alterations in the skin of patients with rosacea. Thus, we aimed to investigate the barrier alterations in papulopustular rosacea samples compared with healthy sebaceous glanderich skin, using RNA sequencing analysis (n ¼ 8). Pathway analyses by Cytoscape ClueGO revealed 15 significantly enriched pathways related to skin barrier formation. RT-PCR and immunohistochemistry were used to validate the pathway analyses. The results showed significant alterations in barrier components in papulopustular rosacea samples compared with sebaceous glanderich skin, including the cornified envelope and intercellular lipid lamellae formation, desmosome and tight junction organizations, barrier alarmins, and antimicrobial peptides. Moreover, the barrier damage in papulopustular rosacea was unexpectedly similar to atopic dermatitis; this similarity was confirmed by immunofluorescent staining. In summary, besides the well-known dysregulation of immunological, vascular, and neurological functions, we demonstrated prominent permeability barrier alterations in papulopustular rosacea at the molecular level, which highlight the importance of barrier repair therapies for rosacea

Immunotopographical Differences of Human Skin

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