Claudia Neumann

Bio: Claudia Neumann is an academic researcher from University of Kiel. The author has contributed to research in topics: Transepidermal water loss & Filaggrin. The author has an hindex of 8, co-authored 12 publications receiving 732 citations.

Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis.

Abstract: Background Genetic defects leading to skin barrier dysfunction were recognized as risk factors for atopic dermatitis (AD) It is essential that drugs applied to patients with AD restore the impaired epidermal barrier to prevent sensitization by environmental allergens Objectives We investigated the effect of 2 common treatments, a calcineurin inhibitor and a corticosteroid, on the skin barrier Methods In a randomized study 15 patients with AD were treated on one upper limb with pimecrolimus and on the other with betamethasone twice daily for 3 weeks Results Stratum corneum hydration and transepidermal water loss, a marker of the inside-outside barrier, improved in both groups Dye penetration, a marker of the outside-inside barrier, was also reduced in both drugs Electron microscopic evaluation of barrier structure displayed prevalently ordered stratum corneum lipid layers and regular lamellar body extrusion in pimecrolimus-treated skin but inconsistent extracellular lipid bilayers and only partially filled lamellar bodies after betamethasone treatment Both drugs normalized epidermal differentiation and reduced epidermal hyperproliferation Betamethasone was superior in reducing clinical symptoms and epidermal proliferation; however, it led to epidermal thinning Conclusion The present study demonstrates that both betamethasone and pimecrolimus improve clinical and biophysical parameters and epidermal differentiation Because pimecrolimus improved the epidermal barrier and did not cause atrophy, it might be more suitable for long-term treatment of AD

Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

Abstract: Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.

The skin: an indispensable barrier

Abstract: The skin forms an effective barrier between the organism and the environment preventing invasion of pathogens and fending off chemical and physical assaults, as well as the unregulated loss of water and solutes In this review we provide an overview of several components of the physical barrier, explaining how barrier function is regulated and altered in dermatoses The physical barrier is mainly localized in the stratum corneum (SC) and consists of protein-enriched cells (corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes) and lipid-enriched intercellular domains The nucleated epidermis also contributes to the barrier through tight, gap and adherens junctions, as well as through desmosomes and cytoskeletal elements During epidermal differentiation lipids are synthesized in the keratinocytes and extruded into the extracellular domains, where they form extracellular lipid-enriched layers The cornified cell envelope, a tough protein/lipid polymer structure, resides below the cytoplasmic membrane on the exterior of the corneocytes Ceramides A and B are covalently bound to cornified envelope proteins and form the backbone for the subsequent addition of free ceramides, free fatty acids and cholesterol in the SC Filaggrin is cross-linked to the cornified envelope and aggregates keratin filaments into macrofibrils Formation and maintenance of barrier function is influenced by cytokines, 3',5'-cyclic adenosine monophosphate and calcium Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis A disturbed skin barrier is important for the pathogenesis of contact dermatitis, ichthyosis, psoriasis and atopic dermatitis

Filaggrin Mutations Associated with Skin and Allergic Diseases

Abstract: Mutations in the filaggrin gene are associated with a broad range of skin and allergic diseases. The biology of this molecule and the role of mutations in its altered function offer new insights into a range of conditions not previously thought to be related to one another.

Atopic Dermatitis: A Disease of Altered Skin Barrier and Immune Dysregulation

Abstract: Atopic dermatitis (AD) is an important chronic or relapsing inflammatory skin disease that often precedes asthma and allergic disorders. New insights into the genetics and pathophysiology of AD point to an important role of structural abnormalities in the epidermis as well as immune dysregulation not only for this skin disease but also for the development of asthma and allergies. Patients with AD have a unique predisposition to colonization or infection by microbial organisms, most notably Staphylococcus aureus and herpes simplex virus. Measures directed at healing and protecting the skin barrier and addressing the immune dysregulation are essential in the treatment of patients with AD, and early intervention may improve outcomes for both the skin disease as well as other target organs.

Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer.

Abstract: Cytokine receptors, which exist in membrane-bound and soluble forms, bind their ligands with comparable affinity. Although most soluble receptors are antagonists and compete with their membrane-associated counterparts for the ligands, certain soluble receptors are agonists. In these cases, complexes of ligand and soluble receptor bind on target cells to second receptor subunits and initiate intracellular signaling. The soluble receptors of the interleukin (IL)-6 family of cytokines (sIL-6R, sIL-11R, soluble ciliary neurotrophic factor receptor) are agonists capable of transmitting signals through interaction with the universal signal-transducing receptor for all IL-6 family cytokines, gp130. In vivo, the IL-6/sIL-6R complex stimulates several types of cells, which are unresponsive to IL-6 alone, as they do not express the membrane IL-6R. We have named this process trans-signaling. The generation of soluble cytokine receptors occurs via two distinct mechanisms-limited proteolysis and translation-from differentially spliced mRNA. We have demonstrated that a soluble form of the IL-6 family signaling receptor subunit gp130, which is generated by differential splicing, is the natural inhibitor of IL-6 trans-signaling responses. We have shown that in many chronic inflammatory diseases, including chronic inflammatory bowel disease, peritonitis, rheumatoid arthritis, asthma, as well as colon cancer, IL-6 trans-signaling is critically involved in the maintenance of a disease state, by promoting transition from acute to chronic inflammation. Moreover, in all these models, the course of the disease can be disrupted by specifically interfering with IL-6 trans-signaling using the soluble gp130 protein. The pathophysiological mechanisms by which the IL-6/sIL-6R complex regulates the inflammatory state are discussed.