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The recombinant murine IgG2a antibody TA99, directed against a melanoma antigen, was used to study combination modalities that potentiate antibody-dependent cell cytotoxicity (ADCC). As previously reported, IgG2a(TA99) was extremely efficacious in preventing the growth of B16 lung metastases. However, the same antibody only mediated a minimal tumor growth retardation, when used to treat established neoplastic masses. The therapeutic activity of IgG2a(TA99) could be substantially enhanced by co-administration with an antibody-cytokine fusion (TA99-mTNF), consisting of the TA99 antibody in scFv format fused to murine TNF.
Group A Streptococcus causes severe invasive infections, including necrotizing fasciitis. The expression of an array of virulence factors targeting specific host immune functions impedes successful bacterial clearance. The virulence factor streptococcal DNase Sda1 was previously shown to interfere with the entrapment of bacteria through neutrophil extracellular traps and TLR9 signaling. In this study, we showed that plasmacytoid dendritic cells are recruited to the infected tissue during group A streptococcal necrotizing fasciitis.
Genetic variation in the NFκB inhibitors, ABIN1 and A20, increase risk for psoriasis. While critical for hematopoietic immune cell function, these genes are believed to additionally inhibit psoriasis by dampening inflammatory signaling in keratinocytes. We dissected ABIN1 and A20’s regulatory role in human keratinocyte inflammation using an RNA-seq based comparative genomic approach. Here we show subsets of the IL-17 and TNFα signaling pathways are robustly restricted by A20 overexpression. In contrast, ABIN1 overexpression inhibits these genes more modestly for IL-17, and weakly for TNFα.
Dipeptidyl-peptidase-IV-inhibitors have been suspected to induce bullous pemphigoid (BP). The objective of this study was to compare the observed frequency of gliptin intake in a large sample of 1787 BP patients diagnosed between 2012 and 2015 in France, with the expected frequency after indirect age standardization on 225412 individuals extracted from the database of the National Healthcare Insurance Agency. The secondary objective was to assess the clinical characteristics and the course of gliptin-associated BP depending on whether gliptin was continued or stopped.
Early diagnosis improves melanoma survival, yet the histopathological diagnosis of cutaneous primary melanoma can be challenging even for expert dermatopathologists. Analysis of epigenetic alterations, such as DNA methylation, that occur in melanoma can aid in its early diagnosis. Using a genome-wide methylation screen, we assessed CpG methylation in a diverse set of 89 primary invasive melanomas, 73 nevi, and 41 melanocytic proliferations of uncertain malignant potential, classified based on interobserver review by dermatopathologists.
Psoriasis lesions are rich in IL-17-producing T-cells as well as neutrophils, which release webs of DNA-protein complexes known as neutrophil extracellular traps (NETs). Because we and others have observed increased NETosis in psoriatic lesions, we hypothesized that NETs contribute to increased Th17 cells in psoriasis. After stimulating peripheral blood mononuclear cells (PBMCs) with anti-CD3/CD28 beads for 7 days, we found significantly higher percentages of CD3+CD4+IL-17+ (Th17) cells in the presence vs.
Evidence-based healthcare requires that relevant outcomes for patients are included in clinical trials investigating treatment effects allowing subsequent systematic reviews to summarize all relevant evidence to guide clinical practice. Currently, no gold standard of outcome choice for dermatology trials and reviews exists. We systematically assessed concordance between efficacy outcomes in a random sample of 10 Cochrane Skin systematic reviews and the 220 dermatology trials included. Reviews did not include 742 (68%) of the 1,086 trial outcomes.
Transient receptor potential (TRP) channels respond to various chemical and physical stimuli by mediating cation influx. The skin expresses abundant TRP channels of different subtypes, which play an essential role in the maintenance of skin functionality. Here, we report cases of mutations in TRPM4 which encodes TRP melastatin 4 (TRPM4), a Ca2+-activated monovalent cation channel, as a cause of an autosomal-dominant form of progressive symmetric erythrokeratoderma (PSEK). In three separate families with PSEK, we identified two missense mutations (c.3099C>G and c.3119T>C) that produce p.Ile1033Met and p.Ile1040Thr, both of which are located in the S6 transmembrane domain of TRPM4 protein.
Hidradenitis suppurativa (HS; also designated as acne inversa) is a chronic inflammatory disease characterized by painful purulent skin lesions and progressive destruction of skin architecture. Despite the high burden for the patients, pathogenetic pathways underlying HS alterations remain obscure. Investigating the lesional HS cytokine pattern, IL-1β turned out as a highly prominent cytokine, being overexpressed even compared to psoriatic lesions. Analyses of IL-1β-induced transcriptome in various cell types disclosed an overlap of upregulated molecules causing immune cell infiltration and extracellular matrix degradation, as well as of specific cytokines including IL-6, IL-32, and IL-36.
and Purpose: A phase 2, double-blind, placebo-controlled trial evaluated apremilast efficacy, safety, and pharmacodynamics in adults with moderate to severe atopic dermatitis (AD).
Some previously described environmental associations for atopic eczema (AE) may be due to reverse causation. We explored the role of reverse causation by comparing individual- and school-level results for multiple AE risk factors.ISAAC Phase Three surveyed children within schools (the sampling unit) on AE symptoms and potential risk factors. We assessed the effect of these risk factors on AE symptoms using mixed-effect logistic regression models, first with individual-level exposure data and second with school-level exposure prevalence.
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