No abstract

SUMMARYBackground: Pemphigus vulgaris (PV) is an autoimmune disease characterized by mucocutaneous intraepithelial blisters and pathogenic autoantibodies against desmoglein 3. There are two clinical forms: mucosal (MPV) and mucocutaneous (MCPV). The frequency of ear, nose and throat (ENT) involvement in PV is not clearly defined. Only a few isolated individual cases have been reported.

Background: Approximately 35–40% of patients with chronic urticaria have an IgG autoantibody to the IgE receptor which can activate basophils and mast cells so that they release histamine. In this study we assessed the cytokine profile present in chronic urticaria sera, and then measured cytokine and leukotriene release from basophils and mast cells upon incubation with chronic urticaria sera. Finally we assessed cytokine expression at the single-cell level and characterized the T cell subpopulations involved in their production. We chose IL-4 as representative of Th2 lymphocytes and IFN-γ for Th1 lymphocytes. Methods: We analyzed IL-4, IL-5 and IFN-γ in 60 chronic urticaria sera versus 51 controls. Sera were incubated with purified human basophils and cutaneous mast cells and the release of histamine, IL-4 and leukotrienes (C₄, D₄, E₄) was quantitated. Immunoblotting was performed to identify IgG antibody to FcΕRIα, α subunit. We measured intracellular cytokine production in peripheral blood mononuclear cells of 17 chronic urticaria patients compared to 50 healthy controls. Results: We found higher IL-4 levels (p = 0.028) in the sera of chronic urticaria patients (1.03 pg/ml) versus healthy donors (0.20 pg/ml) but no difference between urticaria sera and atopic control sera (0.52 pg/ml). We did not detect IFN-γ or IL-5 in any serum. However, sera that activated basophils so that they released histamine also produced leukotriene and IL-4, and leukotriene production by cutaneous mast cells and basophils was closely correlated. However, there was no correlation between immunoblotting and the functional ability to induce either histamine or IL-4. After stimulating with PMA-ionomycin we found significant differences in CD4+ lymphocyte production of IL-4 and IFN-γ with no differences in CD8+ lymphocyte production of either cytokine. Conclusion: Our data support the presence of basophil and mast cell activators in the sera of patients with chronic urticaria which can lead to the production of leukotrienes and IL-4 in addition to the histamine. IL-4 levels are similar to those seen in atopic subjects. We found that CD4+ T cells from patients with chronic urticaria are activated and tend to produce higher cytokine levels than CD4+ T cells from healthy controls. There were no differences when cytokine production by CD8+ lymphocytes was similarly assessed. These results are consistent with the histology found in biopsies of chronic urticaria lesions, where a CD4+-predominant infiltrate is found with cytokine production suggesting either a Th0 response or a mixture of Th1 and Th2 lymphocytes.

An age-dependent decrease in T cell responsiveness to CD28 costimulation has been described. In order to test the hypothesis that an age-related decrease in CD28 expression by CD8+ T lymphocytes might be involved, we analysed 67 healthy donors ranging in age from 15 to 69 years for their CD8+ T cell expression of CD28 and CD57. We found a statistically significant decrease of CD28 expression through ageing and a significant increase of CD57 expression, both markers being mutually exclusive. Given that cytomegalovirus (CMV) is reported to induce CD57 expression, and since the carrier status for this ubiquitous virus increases with age in the general population, it seemed essential to evaluate whether the phenotypic age-related changes described in CD8high+ cells were not influenced by the CMV carrier status of the individuals. Accordingly, we performed a multivariate analysis to assess the independent association of age and CMV carrier status with CD28 and CD57 expression in CD8high+ cells. Results showed that the progressive decrease in CD8high+ CD28+ CD57- cells was associated only with age, while the expansion of the CD8high+ CD28- CD57+ subset depended both on age and CMV, although mainly on age. We conclude that ageing is accompanied by a progressive loss of CD28 expression in CD8+ T cells and a reciprocal enhancement of CD57 expression, both facts being probably related to the repeated antigenic stimulation occurring throughout life.

These findings suggest that angiogenic, coagulation and endothelial damage/dysfunction markers are possibly linked in pathogenesis of extensive slow-flow vascular malformations, and might have therapeutic implications.