Eczematous plaques in a patient with liver failure. Fat-soluble vitamin K hypersensitivity.
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Biomedical subjects
Publications and source records attributed to S Gellis.
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The regulatory influence of atopic eczema and non-atopic T cells on spontaneous IgE synthesis by eczema B cells was examined. Eczema B cells were cocultured with either autologous or allogeneic T cells in RPMI 1640 with 10% fetal calf serum at 0.75 X 10(6) cells/ml (B/T = 0.5) and supernatant IgE was measured by a modified PRIST assay. Net IgE synthesis was obtained by subtracting preformed IgE (+ cycloheximide at Day 0) from total IgE in 7-day supernatants. T cells were either untreated, heat-killed, exposed to 2000 rad, or depleted of helper/suppressor T cells by "panning" with monoclonal antibodies (Leu 3a and Leu 2a). Atopic eczema B cells spontaneously synthesized IgE when cultured alone. No significant suppression of net IgE synthesis occurred when atopic eczema T cells were cocultured with autologous B cells. In allogeneic recombinations, non-atopic T cells significantly suppressed net IgE synthesis by atopic eczema B cells (mean suppression = 59%; P less than 0.05). This suppression was abrogated if allogeneic control T cells were heat-killed, irradiated, or depleted of Leu 2a+ suppressor cells. In order to exclude an "allogeneic effect" as the sole mechanism to explain the suppression of IgE synthesis observed by coculturing non-atopic T cells with eczema B cells, the latter were recombined with either T cells from HLA-DR and mixed lymphocyte culture-matched sibling or autologous T cells. Greater suppression of net IgE synthesis was seen in the presence of histoidentical non-atopic T cells than in the presence of autologous eczema T cells, indicating that the latter have a partial defect in their suppressor function. This apparent "defect" in immunoregulatory function may be overcome by in vitro activation of atopic eczema T cells by concanavalin A.
The effect of dexamethasone (DM) on de novo in vitro total IgE synthesis by blood mononuclear cells (MNC) was studied in atopic patients with eczema and in nonatopic control subjects. Unfractionated blood MNC were cultured at 1 X 10(6) cells per milliliter for 7 days in RPMI 1640 with 10% fetal calf serum with or without decreasing concentrations of DM (10(-7) to 10(-11). Net IgE synthesis was calculated by subtracting preformed (+ cycloheximide at day 0) from total IgE in 7-day supernatants. Supernatant IgE was measured by use of a modified PRIST assay. A significant increase in net IgE synthesis occurred in the presence of DM in 11 of 11 atopic patients with eczema (mean percent increase = 68%; p less than 0.05) and five of five atopic patients without eczema (mean percent increase = 53%; p 0.05) but not in seven of seven nonatopic controls. This increase in de novo IgE synthesis could not be explained by a significant change in cell viability. In five of five experiments, a mean increase of 78% was still noted when DM was added to atopic blood MNCs depleted of T cells by sheep red blood cell rosetting. The addition of 10(-9)M of DM to eczema B+ T cell recombinations enriched for suppressor cells (depleted of Leu 3a+ helper T cells) resulted in a loss of suppressor-T cell activity and maximal augmentation of IgE synthesis. Enhancement of IgE synthesis was also noted when DM was added to eczema B+ T cell recombinations enriched for helper T cells (depleted of suppressor Leu 2a+ T cells).(ABSTRACT TRUNCATED AT 250 WORDS)
Hyper-IgE syndrome (HIE) appears to be related to an immunoregulatory imbalance characterized by severe deficiency of suppressor T cells, elevated levels of IgE antibodies, and repeated infection of various organ systems. We report the association of HIE syndrome in two definite cases and one probable case of vernal conjunctivitis. This association suggests that T cell-mediated imbalance may be one factor in the pathogenesis of vernal conjunctivitis.
Skin involvement in cytomegalovirus (CMV) infection is very rare. Reported cutaneous manifestations are nonspecific and include petechial, purpuric, and morbilliform rashes. We describe an immunocompromised patient who developed a vesiculobullous eruption. A simple Tzanck preparation from the base of a blister revealed multinucleate giant cells suggestive of a viral infection. Subsequent viral cultures and electron microscopic studies confirmed the diagnosis of CMV infection. Consideration of this infection should be included in the differential diagnosis of multinucleate giant cells seen on Tzanck preparations of cutaneous vesicles.
In vitro IgE synthesis by blood mononuclear cells from atopic patients and nonatopic subjects was examined. A total of 1 X 10(6) mononuclear cells cultured in RPMI-1640 and 10% fetal calf serum with or without cycloheximide was found to be optimal to detect de novo synthesis. A modified Phadebas IgE paper radioimmunosorbent test was employed for the quantitation of supernatant IgE concentration. Kinetic studies indicated that about half the peak amount of IgE is secreted within the first 2 days and the maximum concentration is reached at day 7. Mononuclear cells obtained from six of six atopic patients with eczema and elevated serum IgE levels and 22/33 atopic patients without eczema spontaneously synthesized significant amounts of IgE in vitro. We failed to detect de novo IgE synthesis by the cells obtained from 40 nonatopic controls. Polyclonal activators such as pokeweed mitogen. Staphylococcus aureus Cowan I, concanavalin A, and phytohemagglutinin failed to induce or enhance in vitro IgE synthesis in normal and atopic subjects. These findings indicate that the study of immunoregulation of IgE synthesis in man will be difficult to accomplish until new methods are developed that allow induction of the IgE response in vitro in nonatopic subjects.
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