Recessive Dystrophic Epidermolysis Bullosa Patients Research Articles

Surgical Management of Psudosyndactyly in Recessive Dystrophic Epidermolysis Bullosa: About Three Case Reports

Recessive dystrophic epidermolysis bullosa (RDEB) is defined as a congenital disorder resulting from mutations in the COL7A1 gene, often resulting in hand contractures and pseudosyndactyly. While multiple treatments exist to improve hand malformations, there are currently still no radical cures for this disease because of its high recurrence rate. This paper reports our experience of management of hand deformities in three cases of Recessive dystrophic epidermolysis bullosa patients with surgical management and postoperative skin dressings. Hand function was significantly improved after the complete release of pseudosyndactyly and the achievement of satisfying digital web spaces. Patients were followed up for one year and showed good results after functional hand training activities.

Elevated expression of interleukin-6 (IL-6) and serum amyloid A (SAA) in the skin and the serum of recessive dystrophic epidermolysis bullosa: Skin as a possible source of IL-6 through Toll-like receptor ligands and SAA.

The effect of persistent skin inflammation on extracutaneous organs and blood is not well studied. Patients with recessive dystrophic epidermolysis bullosa (RDEB), a severe form of the inherited blistering skin disorder, have widespread and persistent skin ulcers, and they develop various complications including anaemia, hyperglobulinaemia, hypoalbuminaemia and secondary amyloidosis. These complications are associated with the bioactivities of IL-6, and the development of secondary amyloidosis requires the persistent elevation of serum amyloid A (SAA) level. We found that patients with RDEB had significantly higher serum levels of IL-6 and SAA compared to healthy volunteers and patients with psoriasis or atopic dermatitis. Both IL-6 and SAA were highly expressed in epidermal keratinocytes and dermal fibroblasts of the skin ulcer lesions. Keratinocytes and fibroblasts surrounding the ulcer lesions are continuously exposed to Toll-like receptor (TLR) ligands, pathogen-associated and damage-associated molecular pattern molecules. Invitro, TLR ligands induced IL-6 expression via NF-κB in normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts (NHDFs). SAA further induced the expression of IL-6 via TLR1/2 and NF-κB in NHEKs and NHDFs. The limitation of this study is that NHEKs and NHDFs were not derived from RDEB patients. These observations suggest that TLR-mediated persistent skin inflammation might increase the risk of IL-6-related systemic complications, including RDEB.

Intravenous gentamicin therapy induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients: An open label clinical trial.

Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable widespread blistering skin disorder caused by mutations in the gene encoding for type VII collagen (C7), the major component of anchoring fibrils. To evaluate the efficacy and safety of intravenous (IV) gentamicin-readthrough therapy in patients with RDEB harboring nonsense mutations. Primary outcomes were increased expression of C7 in patients' skin and assessments for safety (ototoxicity, nephrotoxicity, autoimmune response). Secondary outcomes included measuring wound healing in target wounds and assessment by a validated Epidermolysis Bullosa Disease and Activity Scarring Index (EBDASI) scoring system. An open-label pilot trial assessing two different regimens of IV gentamicin between August 2018 and March 2020 with follow-up through 180 days post-treatment. Three RDEB patients with confirmed nonsense mutations in COL7A1 in either one or two alleles and decreased baseline expression of C7 at the dermal-epidermal junction (DEJ) of their skin participated in the study. Three patients received gentamicin at 7.5 mg/kg daily for 14 days and two of three patients further received 7.5 mg/kg IV gentamicin twice weekly for 12 weeks.Patients who had pre-existing auditory or renal impairment, were currently using ototoxic or nephrotoxic medications, or had allergies to aminoglycosides or sulfate compounds were excluded. After gentamicin treatment, skin biopsies from all three patients (ages ranging 18-28 years) exhibited increased C7 in their DEJ. With both regimens, the new C7 persisted at least six months post-treatment. At one and three-months post-treatment, 100% of the monitored wounds exhibited greater than 85% closure. Both IV gentamicin infusion regimens decreased EBDASI total activity scores. Of all patients assessed with the EBDASI, all patients exhibited decreased total activity scores three-month post-treatment. All three patients completed the study, and no adverse effects or anti-C7 antibodies were detected. IV gentamicin induced readthrough of nonsense mutations in RDEB patients and restored functional C7 in their skin, enhanced wound healing, and improved clinical parameters. IV gentamicin may be a safe, efficacious, low cost, and readily available therapy in this population of RDEB patients. Clinicaltrials.gov Identifiers: NCT03392909.

Mechanism underlying pruritus in recessive dystrophic epidermolysis bullosa: Role of interleukin-31 from mast cells and macrophages.

Pruritus is a highly burdensome symptom in patients with epidermolysis bullosa, especially recessive dystrophic epidermolysis bullosa (RDEB); however, only a few studies have assessed the molecular pathogenesis of RDEB-associated pruritus. Interleukin (IL)-31 is a key cytokine implicated in pruritus associated with dermatologic diseases such as atopic dermatitis and prurigo nodularis. To investigate the role and cellular source of IL-31 in RDEB-associated pruritus. Serum and skin samples were obtained from 11 RDEB patients and 11 healthy controls. Pruritus visual analogue scale scores were determined. Serum levels of IL-31 and thymic stromal lymphopoietin (TSLP) were examined by enzyme-linked immunosorbent assay (ELISA). The expression of IL-31 and other pruritus mediators in the skin were examined through immunofluorescence staining, and their correlation with pruritus severity was analysed. Serum IL-31 and TSLP were elevated in RDEB patients. IL-31 expression was increased in RDEB skin and positively correlated with pruritus severity. Most of the IL-31-expressing cells were mast cells, and some were CD206(+) M2-like macrophages. The number of substance P(+) cells was also increased in the patients' skin, and most of them were mast cells. The number of substance P(+) mast cells was correlated with the number of IL-31(+) dermal infiltrates. The number of IL-4Rα- and IL-13-expressing cells and expression of TSLP and periostin increased in RDEB skin, but without a correlation to pruritus score. The increased production of skin IL-31 from mast cells and M2-like macrophages may be the mechanism underlying pruritus in RDEB.

CRISPR-Cas9-based non-viral gene editing therapy for topical treatment of recessive dystrophic epidermolysis bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is an autosomal monogenic skin disease caused by mutations in COL7A1 gene and lack of functional type VII collagen (C7). Currently, there is no cure for RDEB, and most of the gene therapies under development have been designed as exvivo strategies because of the shortage of efficient and safe carriers for gene delivery. Herein, we designed, synthesized, and screened a new group of highly branched poly(β amino ester)s (HPAEs) as non-viral carriers for the delivery of plasmids encoding dual single-guide RNA (sgRNA)-guided CRISPR-Cas9 machinery to delete COL7A1 exon 80 containing the c.6527dupC mutation. The selected HPAEs (named PTTA-DATOD) showed robust transfection efficiency, comparable with or surpassing that of leading commercial gene transfection reagents such as Lipofectamine 3000, Xfect, and jetPEI, while maintaining negligible cytotoxicity. Furthermore, CRISPR-Cas9 plasmids delivered by PTTA-DATOD achieved efficient targeted deletion and restored bulk C7 production in RDEB patient keratinocyte polyclones. The non-viral CRISPR-Cas9-based COL7A1 exon deletion approach developed here has great potential to be used as a topical treatment for RDEB patients with mutations in COL7A1 exon 80. Besides, this therapeutic strategy can easily be adapted for mutations in other COL7A1 exons, other epidermolysis bullosa subtypes, and other genetic diseases.

Inflammation-mediated fibroblast activation and immune dysregulation in collagen VII-deficient skin.

Inflammation is known to play a critical role in all stages of tumorigenesis; however, less is known about how it predisposes the tissue microenvironment preceding tumor formation. Recessive dystrophic epidermolysis bullosa (RDEB), a skin-blistering disease secondary to COL7A1 mutations and associated with chronic wounding, inflammation, fibrosis, and cutaneous squamous cell carcinoma (cSCC), models this dynamic. Here, we used single-cell RNA sequencing (scRNAseq) to analyze gene expression patterns in skin cells from a mouse model of RDEB. We uncovered a complex landscape within the RDEB dermal microenvironment that exhibited altered metabolism, enhanced angiogenesis, hyperproliferative keratinocytes, infiltration and activation of immune cell populations, and inflammatory fibroblast priming. We demonstrated the presence of activated neutrophil and Langerhans cell subpopulations and elevated expression of PD-1 and PD-L1 in T cells and antigen-presenting cells, respectively. Unsupervised clustering within the fibroblast population further revealed two differentiation pathways in RDEB fibroblasts, one toward myofibroblasts and the other toward a phenotype that shares the characteristics of inflammatory fibroblast subsets in other inflammatory diseases as well as the IL-1-induced inflammatory cancer-associated fibroblasts (iCAFs) reported in various cancer types. Quantitation of inflammatory cytokines indicated dynamic waves of IL-1α, TGF-β1, TNF, IL-6, and IFN-γ concentrations, along with dermal NF-κB activation preceding JAK/STAT signaling. We further demonstrated the divergent and overlapping roles of these cytokines in inducing inflammatory phenotypes in RDEB patients as well as RDEB mouse-derived fibroblasts together with their healthy controls. In summary, our data have suggested a potential role of inflammation, driven by the chronic release of inflammatory cytokines such as IL-1, in creating an immune-suppressed dermal microenvironment that underlies RDEB disease progression.

Metformin shows anti-neoplastic properties by inhibition of oxidative phosphorylation and glycolysis in epidermolysis bullosa-associated aggressive cutaneous squamous cell carcinoma.

While most cutaneous squamous cell carcinomas (cSCCs) are treatable, certain high-risk cSCCs, such as those in recessive dystrophic epidermolysis bullosa (RDEB) patients, are particularly aggressive. Owing to repeated wounding, inflammation and unproductive healing, RDEB patients have a 68% cumulative risk of developing life-threatening cSCCs by the age of 35, and a 70% risk of death by the age of 45. Despite aggressive treatment, cSCC represents the leading cause of premature mortality in these patients, highlighting an unmet clinical need. Increasing evidence points to a role of altered metabolism in the initiation and maintenance of cSCC, making metabolism a potential therapeutic target. We sought to determine the feasibility of targeting tumour cell energetics as a strategy to selectively hinder the growth advantage of aggressive cSCC. We evaluated the cell energetics profiles of RDEB-SCC cells by analysing available gene expression data against multiple gene signatures and single-gene targets linked to metabolic reprogramming. Additionally, we employed real-time metabolic profiling to measure glycolysis and respiration in these cells. Furthermore, we investigated the anti-neoplastic properties of the metformin against human and murine high-risk cSCCs in vitro and in vivo. Gene expression analyses highlighted a divergence in cell energetics profiles between RDEB-SCC and non-malignant RDEB keratinocytes, with tumour cells demonstrating enhanced respiration and glycolysis scores. Real-time metabolic profiling supported these data and additionally highlighted a metabolic plasticity of RDEB-SCC cells. Against this background, metformin exerted an anti-neoplastic potential by hampering both respiration and glycolysis, and by inhibiting proliferation in vitro. Metformin treatment in an analogous model of fast-growing murine cSCC resulted in delayed tumour onset and slower tumour growth, translating to a 29% increase in median overall survival. Our data indicate that metformin exerts anti-neoplastic properties in aggressive cSCCs that exhibit high-risk features by interfering with respiration and glycolytic processes.

Biomarker Discovery in Rare Malignancies: Development of a miRNA Signature for RDEB-cSCC

Machine learning has been proven to be a powerful tool in the identification of diagnostic tumor biomarkers but is often impeded in rare cancers due to small patient numbers. In patients suffering from recessive dystrophic epidermolysis bullosa (RDEB), early-in-life development of particularly aggressive cutaneous squamous-cell carcinomas (cSCCs) represents a major threat and timely detection is crucial to facilitate prompt tumor excision. As miRNAs have been shown to hold great potential as liquid biopsy markers, we characterized miRNA signatures derived from cultured primary cells specific for the potential detection of tumors in RDEB patients. To address the limitation in RDEB-sample accessibility, we analyzed the similarity of RDEB miRNA profiles with other tumor entities derived from the Cancer Genome Atlas (TCGA) repository. Due to the similarity in miRNA expression with RDEB-SCC, we used HN-SCC data to train a tumor prediction model. Three models with varying complexity using 33, 10 and 3 miRNAs were derived from the elastic net logistic regression model. The predictive performance of all three models was determined on an independent HN-SCC test dataset (AUC-ROC: 100%, 83% and 96%), as well as on cell-based RDEB miRNA-Seq data (AUC-ROC: 100%, 100% and 91%). In addition, the ability of the models to predict tumor samples based on RDEB exosomes (AUC-ROC: 100%, 93% and 100%) demonstrated the potential feasibility in a clinical setting. Our results support the feasibility of this approach to identify a diagnostic miRNA signature, by exploiting publicly available data and will lay the base for an improvement of early RDEB-SCC detection.

Variable Outcome of Immunotherapy in Advanced Multiple Cutaneous Squamous Cell Carcinomas in Two Patients with Recessive Dystrophic Epidermolysis Bullosa

Cutaneous squamous cell carcinoma (cSCC) is a major complication of recessive dystrophic epidermolysis bullosa (RDEB) that has high morbidity and mortality rates and unmet therapeutic needs. The aim of this study was to evaluate the molecular pattern of cSCC and the clinical course of immunotherapy in 2 RDEB patients with multiple advanced cSCC. Clinical course and disease staging were evaluated retrospectively. The tumour tissues were subjected to immunohistochemical staining. DNA from the blood and cSCC samples was subjected to massive parallel sequencing, and somatic mutations were determined. Patient 1 survived for over 2 years as disease control was achieved with cemiplimab and intralesional interleukin-2. The target advanced cSCC demonstrated a high rate of somatic mutations and strong expression of the immune markers, indoleamine 2,3-dioxygenase, programmed cell death protein ligand 1, and lymphocyte-activation gene 3. The patient ultimately succumbed to complications of oesophageal carcinoma. Patient 2 had an undifferentiated cSCC on the foot, which displayed a low mutational burden and did not express immune markers. The tumour progressed quickly even with cemiplimab therapy. These 2 cases underscore the challenges of cSCC treatment for RDEB. Multiple tumours with different molecular and immune profiles occur concomitantly or sequentially, and surgical excision is not always possible because of the anatomical and tissue constraints imposed by the disease itself. In conclusion, programmed cell death protein 1 inhibitors are approved and effective in treating metastatic and locally advanced cSCC. Our experience and the literature suggest that cemiplimab is an option in patients with RDEB if surgery is not. Somatic mutations and the immune microenvironment should be characterized to predict therapeutic response, particularly in aggressive undifferentiated tumours.

A pilot, open study to assess efficacy and safety of ON-01910 (rigosertib) in patients with recessive dystrophic epidermolysis bullosa associated locally advanced/metastatic squamous cell carcinoma.

TPS9604 Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is an extremely rare, severe blistering disease driven by mutations in collagen seven (COL7A1). Besides the skin and mucosal blistering, this genodermatosis is also characterized by aggressive cutaneous squamous cell carcinomas (cSCCs) arising from patients’ chronic wounds. The cumulative risk of death from these cSCCs is 70% by age 45. There are limited effective treatment options for advanced (unresectable/metastatic) RDEB-associated cSCCs. While the standard of care for any advanced cSCC is immune checkpoint inhibitors, only half of the treated patients had responses in clinical trials. Their use for RDEB-associated SCCs been limited to case reports, and our own experience has not been positive. Conventional chemotherapy in RDEB-associated cSCC is another proposed treatment strategy, however, case reports demonstrated limited response rates without lasting effects. Currently it is recommended palliatively, although there are concerns about adverse effects. Other existing options are tyrosine kinase inhibitors, resulting in mixed responses to treatment for advanced cSCCs of any type, and epidermal growth factor receptor inhibitors, demonstrating limited effectiveness in a small number of case reports on RDEB-associated cSCCs. More effective therapeutic modalities for advanced/metastatic RDEB-associated cSCCs are needed. We previously demonstrated that RDEB SCC keratinocytes are specifically affected by polo-like kinase-1 (PLK-1) siRNA. Eight PLK-1 inhibitors were screened for cytotoxicity. Of the 8 candidates, ON-01910 was superior as it demonstrated the largest therapeutic window for distinguishing between tumor versus normal cells. The ON-01910 clinical trial is in progress in patients with RDEB with advanced/metastatic cSCCs. Methods: ON-01910 is being evaluated in both oral and intravenous formulations in an open-label, non-randomized phase 2 study in RDEB patients with advanced, treatment resistant cSCC. The trial explores the anti-tumor activity of ON-01910 and evaluates its safety and tolerability. Secondary objectives are to assess the impact on quality of life and to perform biomarker analysis on patient tissue. This study began in August 2021 and is ongoing. One patient is currently enrolled in the oral arm at Thomas Jefferson University in the USA. Safety is assessed according to the CTCAE v5. Tumor response in lymph nodes is determined per the RECIST 1.1 and in skin via clinical examination with serial tumor measurements. Key eligibility criteria include 1) diagnosis of RDEB and associated measurable, advanced cSCC confirmed histologically 2) failure to respond to standard of care including excision for localized disease 3) no concomitant cancer therapies. Clinical trial information: NCT04177498 .

Generation and characterization of induced pluripotent stem cell lines from two patients with recessive dystrophic epidermolysis Bullosa

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare and severe genetic disease responsible for blistering of the skin and mucosa caused by a wide variety of mutations in COL7A1 encoding type VII collagen. We have generated Induced Pluripotent Stem Cells (iPSCs) from two RDEB patients’ fibroblasts harboring homozygous recurrent mutations in COL7A1. Their pluripotent state was confirmed by gene and protein expression of stem cell markers OCT4, SOX2, TRA1/60 and SSEA4. Embryoid body formation followed by immunostaining and TaqMan scorecard analysis confirmed the capacity of RDEB iPSCs to differentiate into cell types from the three germ layers in vitro.

Inherited epidermolysis bullosa dystrophica and squamous cell carcinoma- A case report.

Epidermolysis bullosa dystrophica (EBD) is an inherited disease of the structural proteins in the upper dermis, characterized by blister formation at the site of trauma followed by scarring. Skin fragility and blistering are the hallmarks of this disease. Cutaneous squamous cell carcinoma (cSCC) is a dreadful complication in the epidermolysis bullosa (EB) patients and common cause of death. The recent advances in distinct tumor microenvironment explain the aggressive nature of SCC in recessive Recessive Dystrophic Epidermolysis Bullosa (RDEB) patients and the use of collagen VII re-expression as a possible therapeutic measure. Regular follow-up is a must in preventing complications.

295 Genotype-phenotype correlation analysis in recessive dystrophic epidermolysis bullosa using in situ germline mouse genome editing technique

Recessive dystrophic epidermolysis bullosa (RDEB) is an intractable skin genetic disease characterized by the skin fragility leading to the recurrent blistering. The mutations in COL7A1 gene, encoding type VII collagen (C7) that forms anchoring fibrils, cause RDEB. RDEB patients are known to show variable prognosis, likely influenced by the position of pathogenic mutations. However, as the mutations in COL7A1 gene distribute across the gene without any apparent hotspots and the majority of RDEB patients harbor the mutations in a compound heterozygous manner, the genotype-phenotype correlation is not fully elucidated.

290 Strategies to improve in vivo survival of Mesenchymal Stromal Cells after injection in immunodeficient mice

Recessive dystrophic epidermolysis bullosa (RDEB) is one of the most severe skin diseases and is caused by loss-of-function mutations in COL7A1 encoding type VII collagen (C7). Patients with RDEB suffer since birth from skin and mucosal blistering and develop severe local and systemic complications resulting in a poor prognosis. Mesenchymal stromal cells (MSC) have been shown to have therapeutic potential to improve wound healing and skin inflammation in RDEB patients due to their capacity to express C7 and their anti-inflammatory properties.

304 Sephardic Ancestry in Recessive Dystrophic Epidermolysis Bullosa Individuals Carrying the Prevalent c.6527insC Mutation

Epidermolysis Bullosa is a clinically and genetically heterogeneous rare blistering skin disorder. The most severe variant, Recessive Dystrophic Epidermolysis Bullosa (RDEB), is caused by loss-of-function mutations in the type VII collagen gene (COL7A1). The COL7A1 c.6527insC mutation in RDEB individuals is curiously prevalent and carries a unique genetic history. In this study, approximately 100 RDEB patients with the c.6527insC founder mutation from Spain, France, Argentina, Chile, Colombia, and the USA were investigated to identify common Sephardic ancestry.

ABE8e adenine base editor precisely and efficiently corrects a recurrent COL7A1 nonsense mutation

Base editing introduces precise single-nucleotide edits in genomic DNA and has the potential to treat genetic diseases such as the blistering skin disease recessive dystrophic epidermolysis bullosa (RDEB), which is characterized by mutations in the COL7A1 gene and type VII collagen (C7) deficiency. Adenine base editors (ABEs) convert A-T base pairs to G-C base pairs without requiring double-stranded DNA breaks or donor DNA templates. Here, we use ABE8e, a recently evolved ABE, to correct primary RDEB patient fibroblasts harboring the recurrent RDEB nonsense mutation c.5047 C > T (p.Arg1683Ter) in exon 54 of COL7A1 and use a next generation sequencing workflow to interrogate post-treatment outcomes. Electroporation of ABE8e mRNA into a bulk population of RDEB patient fibroblasts resulted in remarkably efficient (94.6%) correction of the pathogenic allele, restoring COL7A1 mRNA and expression of C7 protein in western blots and in 3D skin constructs. Off-target DNA analysis did not detect off-target editing in treated patient-derived fibroblasts and there was no detectable increase in A-to-I changes in the RNA. Taken together, we have established a highly efficient pipeline for gene correction in primary fibroblasts with a favorable safety profile. This work lays a foundation for developing therapies for RDEB patients using ex vivo or in vivo base editing strategies.

Longitudinal study of wound healing status and bacterial colonisation of Staphylococcus aureus and Corynebacterium diphtheriae in epidermolysis bullosa patients.

Epidermolysis bullosa (EB) is an inherited disorder characterised by skin fragility and the appearance of blisters and wounds. Patient wounds are often colonised or infected with bacteria, leading to impaired healing, pain and high risk of death by sepsis. Little is known about the impact of bacterial composition and susceptibility in wound resolution, and there is a need for longitudinal studies to understand healing outcomes with different types of bacterial colonisation. A prospective longitudinal study of 70 wounds from 15 severe EB patients (Junctional and Recessive Dystrophic EB) from Chile. Wounds were selected independently of their infected status. Wound cultures, including bacterial species identification, composition and Staphylococcus aureus (SA) antibiotic susceptibility were registered. Wounds were separated into categories according to their healing capacity, recognising chronic, and healing wounds. Hundred-one of the 102 wound cultures were positive for bacterial growth. From these, 100 were SA-positive; 31 were resistant to Ciprofloxacin (31%) and only seven were methicillin-resistant SA (7%). Ciprofloxacin-resistant SA was found significantly predominant in chronic wounds (**P < .01). Interestingly, atoxigenic Corynebacterium diphtheriae (CD) was identified and found to be the second most abundant recovered bacteria (31/101), present almost always in combination with SA (30/31). CD was only found in Recessive Dystrophic EB patients and not related to wound chronicity. Other less frequent bacterial species found included Pseudomonas aeruginosa, Streptococus spp. and Proteus spp. Infection was negatively associated with the healing status of wounds.

102 Citrullinated histone H3, a marker for neutrophil extracellular traps, is associated with poorer prognosis in recessive dystrophic epidermolysis bullosa patients with cutaneous squamous cell carcinoma

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe hereditary skin disease characterized by skin and mucosa fragility with blister formation due to type VII collagen deficiency. The major complication in RDEB patients is the development of squamous cell carcinoma (SCC) leading to premature mortality. Our study aims to correlate the immune profiles of SCCs with clinico-histopathological features in a cohort of RDEB patients. The immune cell profile was assessed by immunohistochemical analyses on 33 SCCs from 19 RDEB patients included between March 2016 and December 2021.

090 Inhibition of HMGB1 attenuates the inflammatory response in keratinocytes

Recessive dystrophic epidermolysis bullosa (RDEB) is a blistering skin disease caused by mutations in COL7A1, the gene encoding type VII collagen (C7). RDEB is characterized by chronic wounds and a high incidence of aggressive squamous cell carcinoma (SCC), the leading cause of death in this patient population. High mobility group box 1 (HMGB1) is a serum biomarker of disease severity in RDEB patients that may have a mechanistic role in promoting SCC carcinogenesis. HMGB1 is a chromatin-associated protein that has a dual role as a mediator of DNA repair in the nucleus and a damage-associated molecular pattern that stimulates the innate immune response when secreted extracellularly in response to inflammatory stimuli or cellular damage.

713 The RNA-based reprogramming of renal epithelial cells derived from recessive dystrophic epidermolysis bullosa patients into induced pluripotent stem cells

No effective therapies are available for recessive dystrophic epidermolysis bullosa (RDEB) at this time. Reprogramming adult cells into induced pluripotent stem cells (iPSCs) may allow for the development of new therapies for RDEB. iPSCs can be derived from many cell types, such as fibroblasts, keratinocytes, and blood cells. The isolation of fibroblasts and keratinocytes requires a skin biopsy, an invasive procedure commonly associated with scarring and inflammation, and venipuncture is potentially traumatic for RDEB patients due to the fragility of their skin.