Skin microbiota-associated inflammation precedes autoantibody induced tissue damage in experimental epidermolysis bullosa acquisita

Ellebrecht, Christoph T.; Srinivas, Girish; Bieber, Katja; Banczyk, David; Kalies, Kathrin; Künzel, Sven; Hammers, Christoph M; Baines, John F.; Zillikens, Detlef; Ludwig, Ralf J.; Westermann, Jürgen

doi:10.1016/j.jaut.2015.08.007

Cited by 28 publications

(22 citation statements)

References 46 publications

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“…While in some body sites an increase is microbial diversity is associated with disease states, particularly the vagina (Van de Wijgert et al, 2014), decreased diversity of the microbiome has frequently been correlated with disease and inflammation in the skin (Alekseyenko et al, 2013; Ellebrecht et al, 2016; Seite et al, 2014; Williams & Gallo, 2015), gut (Giloteaux et al, 2016; Sze & Schloss, 2016) and airways (Yu et al, 2015). However it is not known whether decreased diversity in these sites is a cause or merely an indicator of inflammation.…”

Section: Discussionmentioning

confidence: 99%

A longitudinal study of the diabetic skin and wound microbiome

Gardiner

Vicaretti

Sparks

et al. 2017

PeerJ

117

114

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BackgroundType II diabetes is a chronic health condition which is associated with skin conditions including chronic foot ulcers and an increased incidence of skin infections. The skin microbiome is thought to play important roles in skin defence and immune functioning. Diabetes affects the skin environment, and this may perturb skin microbiome with possible implications for skin infections and wound healing. This study examines the skin and wound microbiome in type II diabetes.MethodsEight type II diabetic subjects with chronic foot ulcers were followed over a time course of 10 weeks, sampling from both foot skin (swabs) and wounds (swabs and debrided tissue) every two weeks. A control group of eight control subjects was also followed over 10 weeks, and skin swabs collected from the foot skin every two weeks. Samples were processed for DNA and subject to 16S rRNA gene PCR and sequencing of the V4 region.ResultsThe diabetic skin microbiome was significantly less diverse than control skin. Community composition was also significantly different between diabetic and control skin, however the most abundant taxa were similar between groups, with differences driven by very low abundant members of the skin communities. Chronic wounds tended to be dominated by the most abundant skin Staphylococcus, while other abundant wound taxa differed by patient. No significant correlations were found between wound duration or healing status and the abundance of any particular taxa.DiscussionThe major difference observed in this study of the skin microbiome associated with diabetes was a significant reduction in diversity. The long-term effects of reduced diversity are not yet well understood, but are often associated with disease conditions.

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Section: Discussionmentioning

confidence: 99%

A longitudinal study of the diabetic skin and wound microbiome

Gardiner

Vicaretti

Sparks

et al. 2017

PeerJ

117

114

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“…So far, no data on the source of these mediators have been published. Recent data, however, suggest that the diversity of the cutaneous microbiome has a significant impact on the expression of inflammatory mediators in the skin (392): in immunization-induced experimental EBA, the clinical outcome, i.e., development of clinically manifest disease, was associated with the diversity of the cutaneous microbiome. Mice with a relatively low diversity of cutaneous microbiota developed clinical EBA, while mice with a relatively high diversity were protected from disease induction.…”

Section: Autoantibody-induced Inflammationmentioning

confidence: 99%

Mechanisms of Autoantibody-Induced Pathology

et al. 2017

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Autoantibodies are frequently observed in healthy individuals. In a minority of these individuals, they lead to manifestation of autoimmune diseases, such as rheumatoid arthritis or Graves' disease. Overall, more than 2.5% of the population is affected by autoantibody-driven autoimmune disease. Pathways leading to autoantibody-induced pathology greatly differ among different diseases, and autoantibodies directed against the same antigen, depending on the targeted epitope, can have diverse effects. To foster knowledge in autoantibody-induced pathology and to encourage development of urgently needed novel therapeutic strategies, we here categorized autoantibodies according to their effects. According to our algorithm, autoantibodies can be classified into the following categories: (1) mimic receptor stimulation, (2) blocking of neural transmission, (3) induction of altered signaling, triggering uncontrolled (4) microthrombosis, (5) cell lysis, (6) neutrophil activation, and (7) induction of inflammation. These mechanisms in relation to disease, as well as principles of autoantibody generation and detection, are reviewed herein.

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“…How they affect wound healing is presently unclear. However, it can be expected that there is an intimate crosstalk between the microbiota and residential cells as well as infiltrating immune cells, which together determine the rate and quality of wound healing (Ellebrecht et al, 2016;Srinivas et al, 2013;Trengove et al, 1996). , when comparing oral commensal and pathogenic biofilms, observed that the pathogenic biofilm supresses the innate immune response (inflammatory cytokine release), suggesting that an early immune evasion is taking place in the organotypic gingival mucosa tissue equivalents.…”

Section: Biofilmmentioning

confidence: 99%

Biology of soft tissue repair: gingival epithelium in wound healing and attachment to the tooth and abutment surface

Gibbs

Roffel²,

Meyer³

et al. 2019

eCM

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Epithelium attachment to the tooth or abutment surface is necessary to form a biological seal preventing pathogens and irritants from penetrating the body and reaching the underlying soft tissues and bone, which in turn can lead to inflammation and subsequent bone resorption. The present review investigated oral wound closure and the role of micro-environment, saliva, crevicular fluid and microbiota in wound healing. The importance of the junctional epithelium (peri-implant epithelium) attachment to the abutment surface was investigated. Current research focuses on macro-design, surface-topography, surface-chemistry, materials, coatings and wettability to enhance attachment, since these optimised surface properties are expected to promote keratinocyte attachment and spreading through hemi-desmosome formation. Detailed studies describing the extent of junctional epithelium attachment-e.g. barrier function, hemi-desmosomes, epithelium quality, composition of the external basement membrane or ability of the epithelium to resist microbial penetration and colonisation-are not yet reported in animals due to ethical considerations, scalability, expense, technical challenges and limited availability of antibodies. In vitro studies generally include relatively simple 2D culture models, which lack the complexity required to draw relevant conclusions. Additionally, human organotypic 3D mucosa models are being developed. The present review concluded that more research using these organotypic mucosa models may identify relevant parameters involved in soft-tissueabutment interactions, which could be used to study different macro-shapes and surface modifications. Such studies would bridge the gap between clinical, animal and traditional in vitro cell culture studies supporting development of abutments aiming at improved clinical performance.

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Skin microbiota-associated inflammation precedes autoantibody induced tissue damage in experimental epidermolysis bullosa acquisita

Cited by 28 publications

References 46 publications

A longitudinal study of the diabetic skin and wound microbiome

A longitudinal study of the diabetic skin and wound microbiome

Mechanisms of Autoantibody-Induced Pathology

Biology of soft tissue repair: gingival epithelium in wound healing and attachment to the tooth and abutment surface

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