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  • 1
    In: Clinical Genetics, Wiley, Vol. 98, No. 2 ( 2020-08), p. 116-125
    Abstract: Discoid lupus erythematosus (DLE) is an autoimmune disorder with a poorly defined etiology. Despite epidemiologic gender and ethnic biases, a clear genetic basis for DLE remains elusive. In this study, we used exome and RNA sequencing technologies to characterize a consanguineous Lebanese family with four affected individuals who presented with classical scalp DLE and generalized folliculitis. Our results unraveled a novel biallelic variant c.1313C  〉  A leading to a missense substitution p.(Thr438Asn) in TRAF3IP2 (NM_147200.3). Expression studies in cultured cells revealed mis‐localization of the mutated protein. Functional characterization of the mutated protein showed significant reduction in the physical interaction with the interleukin 17‐A receptor (IL17RA), while interaction with TRAF6 was unaffected. By conducting a differential genome‐wide transcriptomics analysis between affected and non‐affected individuals, we showed that the hair follicle differentiation pathway is drastically suppressed, whereas cytokine and inflammation responses are significantly upregulated. Furthermore, our results were highly concordant with molecular signatures in patients with DLE from a public dataset. In conclusion, this is the first report on a new putative role for TRAF3IP2 in the etiology of DLE. The identified molecular features associated with this gene could pave the way for better DLE‐targeted treatment.
    Type of Medium: Online Resource
    ISSN: 0009-9163 , 1399-0004
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2004581-5
    detail.hit.zdb_id: 221209-2
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  • 2
    In: Photodermatology, Photoimmunology & Photomedicine, Wiley, Vol. 37, No. 3 ( 2021-05), p. 202-213
    Abstract: We hypothesized that upon sun exposure, a sub‐population of primary skin–derived mesenchymal‐like cells is deleteriously affected and thus contribute to the chronic inflammatory state in autosomal recessive variegate porphyria patients. The aim of this study was to isolate and characterize the mesenchymal‐like stem cells from different areas of the skin in a porphyria patient (sun exposed, SE, and sun protected, SP) and to compare them with cells from a healthy individual. Methods The proliferation rate and the migration ability of SE and SP cells were evaluated in the presence of an antioxidant compound, N‐acetylcysteine. A co‐culture of SE‐damaged cells with the conditioned medium from the enriched mesenchymal cell—like SP population was performed in order to regenerate the dermal injured tissue after sun exposure in patients. Results Results showed that the percentage of CD105 + cells varies between 3.9% in SP and 5% in SE of the healthy individual and between 3.6% and 1.4% in SP and SE in the porphyria patient, respectively. The osteogenic differentiation potential was lower in the porphyria patient when compared to the control. Furthermore, the expression of stem cell markers was more pronounced in SE than in SP cells of both control and porphyria. The use of N‐acetyl cysteine did not show any beneficial effects on porphyria SE cells. Treatment with SP‐conditioned medium slightly increased the expression of stem cell markers in SE of porphyria patient. Conclusion In conclusion, the pool of mesenchymal stem—like SE cells is affected in variegate porphyria patient along with modification of their self‐renewal and differentiation properties.
    Type of Medium: Online Resource
    ISSN: 0905-4383 , 1600-0781
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2026222-X
    detail.hit.zdb_id: 1028855-7
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  • 3
    In: Experimental Dermatology, Wiley, Vol. 30, No. 7 ( 2021-07), p. 988-994
    Abstract: Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of multiple inflammatory dermatoses. However, characterization of NETs in neutrophilic dermatoses was performed on very limited number of patients; this limitation precluded definitive conclusions. In this case series of 57 patients, we compared the amounts of neutrophils producing NETs in cutaneous lesions of different entities of neutrophilic dermatoses (17 with pyoderma gangrenosum, 37 with Sweet's syndrome and three with subcorneal pustular dermatosis). NETs were identified by double immunofluorescence on formalin‐fixed paraffin‐embedded skin biopsies using antibodies against elastase and citrullinated histone 3. Percentages of neutrophils showing NETs were high across all three entities (62.9% in PG, 48.5% in SS and 37.8% in subcorneal pustular dermatosis). The differences in mean percentages were significant between entities, with PG showing significantly superior percentage of NETs compared with SS. In our series, 15.8% of neutrophilic dermatoses were associated with malignancies, 10.5% with autoimmune diseases and 73.7% were idiopathic. Percentages of NETs were not statistically different between aetiologies. These findings suggest that NETs are abundantly produced in the various entities and different aetiologies of neutrophilic dermatoses. In comparison with SS, the superior percentage of NETs in PG is clinically mirrored in its greater ulceronecrotic nature.
    Type of Medium: Online Resource
    ISSN: 0906-6705 , 1600-0625
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1130936-2
    detail.hit.zdb_id: 2026228-0
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