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Mecanismos de acción de la inmunoglobulina humana en las enfermedades dermatológicas pediátricas

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    ABSTRACT: Toxic epidermal necrolysis (TEN, Lyell's syndrome) is a severe adverse drug reaction in which keratinocytes die and large sections of epidermis separate from the dermis. Keratinocytes normally express the death receptor Fas (CD95); those from TEN patients were found to express lytically active Fas ligand (FasL). Antibodies present in pooled human intravenous immunoglobulins (IVIG) blocked Fas-mediated keratinocyte death in vitro. In a pilot study, 10 consecutive individuals with clinically and histologically confirmed TEN were treated with IVIG; disease progression was rapidly reversed and the outcome was favorable in all cases. Thus, Fas-FasL interactions are directly involved in the epidermal necrolysis of TEN, and IVIG may be an effective treatment.
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    ABSTRACT: Previous studies identified autoantibodies against the IgE high affinity receptor alpha-chain, Fc epsilon RI alpha, in sera of selected patients with severe chronic idiopathic urticaria. We have now determined the incidence of anti-Fc epsilon RI alpha autoantibodies in a group of 163 patients. Intradermal injection of autologous serum caused skin reactions indicative of mast cell degranulation in 98 (60%) patients. Based on histamine release from IgE-sensitized and nonsensitized basophil leukocytes of healthy donors, we detected anti-Fc epsilon RI alpha autoantibodies in sera from 38 (23%) urticaria patients and evidence for anti-IgE antibodies in a further nine patients. The sera that released histamine from basophils induced histamine release (4-34%, n = 12) from mast cells in incubated skin slices. Protein-G affinity chromatography of sera demonstrated that mast cell histamine release was IgG-mediated. Preincubation of sera or the IgG fraction with a recombinant alpha-chain of Fc epsilon RI inhibited histamine release from mast cells and basophils. Further studies with the mouse anti-human Fc epsilon RI alpha antibody 29C6 showed that mast cells and basophils were similarly sensitive to IgG-mediated direct cross-linking of Fc epsilon RI, with 0.01-1.0 micrograms/ml 29C6 evoking histamine release in each case. These studies demonstrate that circulating levels of anti-Fc epsilon RI alpha autoantibodies mediate histamine release from skin mast cells in vitro and, taken together with in vivo evidence of mast cell degranulation following intradermal injection of autologous serum, support the concept that anti-Fc epsilon RI alpha autoantibodies are relevant to the pathogenesis of severe chronic urticaria in about 25% of patients.
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    ABSTRACT: The pathogenic role of pemphigus autoantibodies and proteinases in epidermal acantholysis has been studied in organ cultures of normal human skin. Dose-dependent acantholysis occurred in skin explants cultured in medium containing 2-30 mg/ml of gamma-globulin from pemphigus serum. Acantholysis was not seen in explants cultured with 2 mg/ml pemphigus gamma-globulin although antibody binding to the epidermis was observed. Some degenerative changes in addition to acantholysis were present when 30 mg/ml pemphigus gamma-globulin was added to the medium. The addition of N,ethylmaleimide(NEM) and ethylene diamine tetraacetate(EDTA) prevented binding of pemphigus antibody to epidermis in culture. Soybean trypsin inhibitor and pepstatin had no effect on binding of pemphigus antibody to the epidermis but they did inhibit acantholysis in vitro. Our results suggest that pemphigus-induced acantholysis may be caused by at least 2 different types of enzyme.
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