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Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Absceso/diagnóstico , Absceso/tratamiento farmacológico , Antibacterianos/uso terapéutico , Exotoxinas , Humanos , Leucocidinas , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureusRESUMEN
Pemphigus vulgaris (PV) is an autoimmune blistering disorder of the skin and/or mucous membranes caused by IgG autoantibodies that predominantly target two transmembrane desmosomal cadherins: desmoglein (DSG)1 and DSG3. DSG-specific T cells play a central role in PV pathogenesis because they provide help to autoreactive B cells for autoantibody production. In this study, we characterized DSG3-specific peripheral T cells in a cohort of 52 patients with PV and 41 healthy controls with regard to cytokine profile and epitope specificity. By ELISpot analysis, type 2 T cells reactive with the DSG3 ectodomain were significantly increased in patients with PV compared with those in healthy controls. By dextramer analysis, CD4+ T cells specific for an epitope within the extracellular domain of DSG3, DSG3(206-220), were found at significantly higher frequencies in patients with PV than in HLA-matched healthy controls. T-cell recognition of two distinct DSG3 epitopes, that is, DSG3(206-220) and DSG3(378-392), correlated significantly, suggesting a synergistic effect in B-cell help. Immunization of HLA-DRB1∗04:02-transgenic mice with PV with the same set of DSG3 peptides induced pathogenic DSG3-specific IgG antibodies, which induced loss of keratinocyte adhesion in vitro. Thus, DSG3 peptide-specific T cells are of particular interest as surrogate markers of disease activity and potential therapeutic targets in PV.
Asunto(s)
Pénfigo , Animales , Humanos , Ratones , Autoanticuerpos , Desmogleína 1 , Desmogleína 3/genética , Epítopos , Inmunoglobulina G , Ratones Transgénicos , PéptidosRESUMEN
Dermatomyositis (DM) is an autoimmune disorder, which belongs to a group of rare autoimmune dermatoses characterized by different skin features and variable muscle involvement. We recognize four main variants of DM: classic DM, clinically amyopathic DM, paraneoplastic DM, and juvenile DM. Clinically, patients show several skin features, but heliotrope rash, and violaceous papules located at the interphalangeal or metacarpophalangeal joints (Gottron's papules) are the most frequently observed. Together with skin features, patients show muscle involvement, most commonly with symmetrical weakness of the proximal muscles. DM belongs to the facultative paraneoplastic dermatoses and a wide range of solid or hematologic malignancies can be detected in DM patients. Serologically, a wide range of autoantibodies can be detected in patients with DM. Indeed, distinct serotypes can be related to specific phenotypes with specific clinical features, carrying a different risk for systemic involvement and for malignancies. Systemic corticosteroids are still considered the first-line approach, but several steroid-sparing agents, such as methotrexate, azathioprine or mycophenolate mofetil, have been reported as effective in treating DM. Furthermore, new class of drugs, such as monoclonal antibodies, purified immunoglobulins or Janus kinase inhibitors are becoming more relevant in the clinical practice or are currently under investigation. In this work, we aim to offer a clinical overview of the diagnostic workout, the characteristics of DM variants, the role of autoantibodies in DM, and the management of this life-threatening systemic disorder.
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Dermatomiositis , Enfermedades de la Piel , Humanos , Dermatomiositis/terapia , Dermatomiositis/tratamiento farmacológico , Piel , Anticuerpos Monoclonales/uso terapéutico , Autoanticuerpos/uso terapéuticoRESUMEN
Introduction: We here thought to dissect the inflammatory signature in lesions of three skin disorders, which show a common adaptive immune response against autoantigens of the skin but are characterized by diverging clinical phenotypes. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are type-2-dependent, IgG autoantibody-driven blistering disorders of mucous membranes and skin, which target desmoglein (Dsg)3 and bullous pemphigoid (BP)180, respectively. In contrast, lichen planus (LP) is a common chronic inflammatory disease of the skin and mucous membranes with a pronounced dermal T cell infiltrate. We previously identified peripheral type 1 and 17 T cell responses against Dsg3 and BP180 in a cohort of LP patients strongly suggesting that the underlying inflammatory T cell signature may drive the evolving phenotype. Methods: Paraffin-embedded skin biopsies from well-characterized patients with LP (n=31), BP (n=19), PV (n=9), and pemphigus foliaceus (PF) (n=2) were analysed. Areas with the most prominent inflammatory infiltrate were excised with punch biopsies and tissue microarrays (TMA) containing multiple biopsies were created. Using multicolor immunofluorescence, the inflammatory infiltrate was stained with antibodies against multiple cellular markers, i. e. CD3ϵ, CD4, CD15, TCR-δ, the cytokine IL-17A, and the transcription factors, T-bet and GATA-3. Results: In LP, there was a higher number of CD4+ T cells expressing T-bet compared to GATA-3. In contrast, CD4+ T cells in PV and BP skin lesions more frequently expressed GATA-3 than T-bet. IL-17A+ cells and IL-17A+ T cells were found to a similar extent in all the three disorders. IL-17A+ granulocytes were more predominant in BP than in LP or PV. Of note, the majority of IL-17A+ cells in LP were neither T cells nor granulocytes. Discussion: Our findings in inflammatory skin infiltrates clearly show a predominant type 1 signature in LP in contrast to a preponderance of type 2 T cells in PV and BP. In contrast to LP, granulocytes and to a much lesser extent CD3+ T cells were a cellular source of IL-17A in BP and PV. These data strongly suggest that different inflammatory cell signatures drive evolving clinically diverse phenotypes of LP, PV and BP despite common target antigens of the skin.
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Liquen Plano , Penfigoide Ampolloso , Pénfigo , Humanos , Interleucina-17 , Autoanticuerpos , Linfocitos T CD4-Positivos/patologíaRESUMEN
Behçet's disease (BD) is a systemic inflammatory disease of unknown etiology. BD is characterized by relapsing oral and genital ulcers, several different cutaneous features, relapsing bilateral uveitis, and involvement of internal organs, showing vascular, gastrointestinal, and neurological manifestations. Serologically, BD is not characterized by disease-specific autoantibodies. In fact, only laboratory markers of inflammation, such as C-reactive protein, may be increased in association with increased disease activity. Bullous pemphigoid (BP) is an autoimmune disease characterized mainly by tense blisters and urticaria-like plaques on the skin. In addition, BP can involve oral mucosa in up to 20% of patients. Patients with BP show serum IgG autoantibodies against BP antigen 180 (BP180) and/or BP antigen 230 (BP230). Tissue-bound autoantibodies can be visualized as linear IgG staining along the basement membrane by direct immunofluorescence microscopy. In this report, we first described a young patient with BD who showed IgG autoantibodies against BP180 without developing blisters or urticaria-like plaques.
RESUMEN
Heat tolerance is commonly assessed as the critical thermal maximum (CTmax) using the dynamic method exposing organisms to a gradually increasing (ramping) temperature until organisms fall into a coma. The CTmax estimate is dependent on the ramping rate, with decreased rates leading to longer treatments and ultimately lower CTmax estimates. There is a current discussion surrounding the physiological dynamics of the effect of the time of exposure by temperature interaction on these estimates. Besides temperature the time of exposure to limited food (starvation), desiccation, and reduced levels of oxygen or increased levels of CO2 may, in interaction with ramping rate, act as confounding factors when assessing upper thermal limits using the dynamic method. Here we test the role of the different potentially confounding factors for assaying thermal tolerance using a ramping assay under four different ramping rates, varying from 0.01⯰C/min to 0.2⯰C/min. We find that CTmax values are higher at faster ramping rates and that oxygen or CO2 concentration does not show any negative effect on the CTmax values obtained within the experimental pre-treatment period (32â¯h). Both water (up to 6â¯h) and food (up to 42â¯h) deprivation prior to assay showed a negative correlation with thermal tolerance of the flies. For both traits, we found a significant interaction with ramping rate, most likely due to prolonged assays at lower rates. However, as little water was lost during the ramping assay and as food deprivation only modestly affected CTmax values, results were very robust to the conditions experienced during the assay (even at slow rates) and mainly affected by the conditions experienced prior to performing the assay. Thus, for the most commonly applied experimental conditions CTmax estimates are unlikely to be biased or confounded by ramping rate, starvation, desiccation or deteriorating atmospheric composition.