Signatures of Dermal Fibroblasts from RDEB Pediatric Patients.

The recessive form of dystrophic epidermolysis bullosa (RDEB) is a debilitating disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Mutations in the COL7A1 gene induce multiple abnormalities, including chronic inflammation and profibrotic changes in the skin. However, the correlations between the specific mutations in COL7A1 and their phenotypic output remain largely unexplored. The mutations in the COL7A1 gene, described here, were found in the DEB register. Among them, two homozygous mutations and two cases of compound heterozygous mutations were identified. We created the panel of primary patient-specific RDEB fibroblast lines (FEB) and compared it with control fibroblasts from healthy donors (FHC). The set of morphological features and the contraction capacity of the cells distinguished FEB from FHC. We also report the relationships between the mutations and several phenotypic traits of the FEB. Based on the analysis of the available RNA-seq data of RDEB fibroblasts, we performed an RT-qPCR gene expression analysis of our cell lines, confirming the differential status of multiple genes while uncovering the new ones. We anticipate that our panels of cell lines will be useful not only for studying RDEB signatures but also for investigating the overall mechanisms involved in disease progression.

Observational study of pimecrolimus 1% cream for prevention of transcutaneous sensitization in children with atopic dermatitis during their first year of life.

Introduction: Epidermal barrier dysfunction in children with atopic dermatitis can cause transcutaneous sensitization to allergens and allergic diseases. We evaluated the effectiveness of an early-intervention algorithm for atopic dermatitis treatment, utilizing pimecrolimus for long-term maintenance therapy, in reducing transcutaneous sensitization in infants. Method: This was a single-center cohort observational study that enrolled children aged 1-4 months with family history of allergic diseases, moderate-to-severe atopic dermatitis, and sensitization to ≥ 1 of the investigated allergens. Patients who sought medical attention at atopic dermatitis onset (within 10 days) were group 1 "baseline therapy with topical glucocorticoids with subsequent transition to pimecrolimus as maintenance therapy"; patients who sought medical attention later were group 2 "baseline and maintenance therapy with topical glucocorticoids, without subsequent use of pimecrolimus". Sensitization class and level of allergen-specific immunoglobulin E were determined at baseline, and 6 and 12 months of age. Atopic dermatitis severity was evaluated using the Eczema Area and Severity Index score at baseline and 6, 9 and 12 months of age. Results: Fifty-six and 52 patients were enrolled in groups 1 and 2, respectively. Compared with group 2, group 1 demonstrated a lower level of sensitization to cow's milk protein, egg white and house dust mite allergen at 6 and 12 months of age, and a more pronounced decrease in atopic dermatitis severity at 6, 9 and 12 months of age. No adverse events occurred. Discussion: The pimecrolimus-containing algorithm was effective in treating atopic dermatitis and prophylaxis of early forms of allergic diseases in infants. Trial registration: https://clinicaltrials.gov/ NCT04900948, retrospectively registered, 25 May 2021.