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The major histocompatibility complex (MHC)-haplotype represents the most prevalent genetic risk factor for the development of autoimmune diseases. However, the mechanisms by which MHC-associated genetic susceptibility translates into autoimmune disease are not fully understood. Epidermolysis bullosa acquisita (EBA) is an autoimmune skin blistering disease driven by autoantibodies to type VII collagen (COL7).Here, we investigated autoantigen-specific plasma cells, CD4+ T cells and IgG Fc-glycosylation in murine EBA in congenic mouse strains with the disease-permitting H2s or -non-permitting H2b MHCII haplotypes.
Squamous cell carcinoma in situ (SCCIS) is a prevalent precancerous lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Although SCCIS is common, its pathogenesis remains poorly understood. To better understand SCCIS development, we performed laser-captured microdissection of human SCCIS and adjacent epidermis to isolate genomic DNA and RNA for next generation sequencing. Whole exome sequencing (WES) identified UV-signature mutations in multiple genes including Notch 1-3 in the epidermis and SCCIS and oncogenic TP53 mutations in SCCIS.
Myriad interventions are available for the treatment of actinic keratoses (AK) located on the face or scalp. However, lesions located outside the head and neck have received little attention until now. We aimed to synthesize the current knowledge of interventions for AK in non-scalp and non-face localizations. Randomized controlled trials (RCTs) reporting data for these localizations were searched in Medline, Embase, and the Cochrane library CENTRAL as well as in pertinent trial registers until 25 March 2020.
With the advent of molecular targeted therapy and immunotherapy, the 5-years survival rate of patients with metastatic melanoma has increased (Jenkins and Fisher, 2020). Despite recent treatment advances, defining novel therapeutic targets for melanoma is still an unmet medical need for patients with resistant to those targeted therapies or immunotherapy. Epigenetic regulators have emerged as therapeutic targets for cancer therapy, of which bromodomain extra-terminal (BET) family protein BRD4 is a key reader protein that recognizes acetylated lysine residues on chromatin.
Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are rare diseases mediated by IgG autoantibody-induced damage of the skin (Kasperkiewicz et al., 2017). These diseases are commonly treated with high-dose systemic corticosteroids. However, patients can have difficulty stopping systemic corticosteroid treatments and often require additional adjunctive immunosuppression, including azathioprine, mycophenolate mofetil, or methotrexate. Rituximab, a monoclonal antibody directed against CD20 on B cells, is an effective first line therapy for patients with pemphigus when compared with prednisone treatment alone, with clinical responses persisting even after B cell recovery (Joly et al.
Interleukin 17A (IL17A), a key cytokine in the inflammation of psoriasis, is upregulated in psoriatic skin and stimulates transcriptional activity correlating with the psoriasis transcriptome (Chiricozzi et al., 2011). Asymmetric stem cell self-renewal (ASR) is increased in psoriasis. IL17A increases ASR in human keratinocytes and ASR divisions are IL17A-dependent in the imiquimod-induced-psoriasis-like mouse model (Charruyer et al., 2017).
Granzyme B-producing CD49a+ CD8 T cells in the lesional skin may reflect the disease prognosis in alopecia areata.
Society for Investigative Dermatology 2020
Graft-versus-host disease is a significant cause of morbidity and mortality following stem cell transplantation. Donor T cells are believed to be the main mediators of disease, however we recently identified that host T cells survive stem cell transplant conditioning and are present in high percentages in skin during active acute GVHD. Host T cells appear to contribute to disease pathology in both human studies and a humanized mouse model. Data further suggested that after resolution of acute GVHD, T cell chimerism in skin shift dramatically to donor T cells.
Fixed drug eruptions (FDE) are a unique form of drug reaction in which a rash recurs at the same skin site(s) with each repeated drug exposure. This intriguing reaction has been postulated to be due to skin resident memory T cells, yet investigation into T cell phenotype and function and the concomitant inflammatory milieu are surprisingly limited. To elucidate disease pathobiology, we performed Nanostring transcriptional profiling on RNA extracted from formalin fixed paraffin embedded skin specimens of active FDE lesions and healthy control skin.
Effective, targeted treatments for guttate psoriasis are lacking. Drugs that block the interleukin-17 (IL-17) pathway are highly effective in the treatment of plaque psoriasis. Given the overlap of immunopathogenic features between guttate and plaque psoriasis, including an over activation of Th17 cells, it is plausible that IL-17A inhibition would be an effective treatment for guttate psoriasis. Ixekizumab, a humanized IgG4 monoclonal antibody that targets interleukin-17A (IL-17A) is FDA-approved for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy, but to our knowledge has never been reported in the treatment of guttate psoriasis.
Upregulation of interferon (IFN) signaling is well documented in the skin, as well as blood and muscle of dermatomyositis (DM) patients. However, it is unclear if IFN signaling is related to the pathologic features commonly found in DM skin biopsies. Here, we investigate the association of Type I and II IFN gene signatures with cardinal histologic findings seen in DM skin to better understand the contribution of IFN signaling to key pathological features of DM. Histological staining and RNA sequencing were performed on 113 skin biopsies from 99 patients with DM.
The type of dermoscopy pattern in post-therapy remaining plaques of early Mycosis Fungoides, might help physicians in selecting the most appropriate therapeutic measures. Dermoscopy is a noninvasive popular technique enhancing the diagnostic ability in Derrmatological practice. “Spermatozoa-like” structures and fine short linear vessels are the most specific dermoscopic diagnostic features of early Mycosis Fungoides. Little is known about their modification following treatment. In a pilot study we prospectively investigated the modifications, if any, of dermoscopy features in 8 patients, who had been treated for at least 1 year.
Allergic contact dermatitis (ACD) affects 20% of patients and combined with irritant contact dermatitis (ICD) account for more than 90% of occupational skin diseases. Patch testing is the gold standard for diagnosis of ACD but result interpretation may be patient and physician dependent. The purpose of this study is to examine whether noninvasive tape stripping can be used to differentiate ACD, ICD, and normal skin. We examined 39 immune and barrier genes expressed in various skin layers. Patients referred to the Massachusetts General Hospital Contact Dermatitis Clinic with confirmed diagnosis of ACD through patch testing were recruited.
Chemotherapy-induced hair loss (alopecia, CIA) remains a major unsolved problem in clinical oncology. CIA is often considered to be a consequence of the anti-mitotic and apoptosis-promoting properties of chemotherapy drugs acting on rapidly proliferating hair matrix keratinocytes. Here we show that in a mouse model of CIA, down-regulation of Shh signalling in the hair matrix is a critical early event. Inhibition of Shh signalling recapitulated key morphological and functional features of CIA, whereas recombinant Shh protein partially rescued hair loss.
The increasing incidence of cutaneous neoplasms in the Caucasian population of the United States has made Mohs micrographic surgery (MMS) and surgical excision with wide margins the standard of care for the treatment of melanoma and non-melanoma skin cancers. These commonly performed surgical modalities promote high cure rates and conservative treatment methods, sparing the maximal amount of normal tissue. Although there is a growing body of evidence regarding the efficacy of dermatological surgery for the removal of cutaneous malignancies, there is still some debate regarding the guidelines for maintaining safety and avoiding complications of MMS and other dermatologic procedures.
The migration of wound-edge keratinocytes is part of the wound response, crucial for complete wound closure. Despite significant advances, the molecular mechanisms that orchestrate cell-cell adhesion between migrating keratinocytes are not fully characterized. During wound re-epithelization, keratinocytes at the wound edge undergo series of cellular modifications. These cellular modifications require a loosening of cell-cell adhesion for effective migration. Mice lacking the epidermal transcription factor Grainyhead Like-3 (GRHL3) exhibit impaired wound healing and an increased adhesion between keratinocytes at the wound edge.
The follicular bulge is a stem cell niche where the outer root sheath (ORS) abuts the arrector pili muscle insertion site in both murine and human hair follicles. Prior studies have recognized an uncommon structure termed the “follicular trochanter” which was described as an epithelial protrusion of the outer root sheath in anagen follicles. It has been shown that these structures prominently express keratin 15, a stem cell marker. We sought to determine if trochanters embedded in the fibrotic stroma contribute to follicular scarring in cicatricial alopecias.