Objective Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by B cell hyperactivity and defective T cell functions, including interleukin‐2 production and proliferation. The defects in T cell function may result from underlying defects in antigen‐presenting cell (APC) function. The present study was undertaken to investigate phenotypic and functional characteristics of peripheral blood dendritic cells (DC), as the most potent APC, in SLE patients in comparison with healthy controls. Methods Samples from 25 SLE patients and 15 healthy controls were studied. To identify DC, peripheral blood mononuclear cells were double stained with monoclonal antibodies against lineage marker (lin)–specific molecules CD3, CD19, CD14, and CD16, versus CD4. DC were characterized phenotypically by flow cytometry. The stimulatory capacity of DC was determined by proliferation of T cells in the mixed lymphocyte reaction (MLR), which was assessed by measurement of tritiated thymidine incorporation in studies using granulocyte–macrophage colony‐stimulating factor–activated, DC‐enriched APC. Correlations between DC counts and phenotype and clinical parameters in SLE patients were determined. Results Lin−,HLA–DR+,CD4+ DC were, on average, 50% less frequent in SLE patients than in controls. Moreover, among DC, the proportions of B7+ and CD40+ cells were reduced and, in particular, the CD11c+ subset was reduced by an average of 80% in SLE patients. Functional analysis of DC‐enriched APC from SLE patients revealed a diminished T cell–stimulatory capacity in both the allogeneic and the antigen‐specific MLR, as compared with healthy individuals. Although the frequencies of DC were weakly inversely correlated with disease activity and/or current treatment protocols, our data suggest a disease‐intrinsic defect. Conclusion The considerable alterations of DC and DC subsets in SLE patients may contribute to the pathogenic mechanisms involved in the disease.
Objective. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by B cell hyperactivity and defective T cell functions, including interleukin-2 production and proliferation. The defects in T cell function may result from underlying defects in antigen-presenting cell (APC) function. The present study was undertaken to investigate phenotypic and functional characteristics of peripheral blood dendritic cells (DC), as the most potent APC, in SLE patients in comparison with healthy controls.Methods. Samples from 25 SLE patients and 15 healthy controls were studied. To identify DC, peripheral blood mononuclear cells were double stained with monoclonal antibodies against lineage marker (lin)-specific molecules CD3, CD19, CD14, and CD16, versus CD4. DC were characterized phenotypically by flow cytometry. The stimulatory capacity of DC was determined by proliferation of T cells in the mixed lymphocyte reaction (MLR), which was assessed by measurement of tritiated thymidine incorporation in studies using granulocyte-macrophage colonystimulating factor-activated, DC-enriched APC. Correlations between DC counts and phenotype and clinical parameters in SLE patients were determined.Results. Lin؊,HLA-DR؉,CD4؉ DC were, on average, 50% less frequent in SLE patients than in controls. Moreover, among DC, the proportions of B7؉ and CD40؉ cells were reduced and, in particular, the
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Cyclosporine is a widely used and potent immunosuppressant drug with a narrow therapeutic index. Therefore, cyclosporine concentrations should be monitored closely. Various automated immunologic methods for cyclosporine whole blood determinations are available. Two new methods, fluorescence polarization immunoassay (FPIA) for the AxSYM by Abbott Laboratories, Chicago, IL, and the cloned enzyme donor immunoassay (CEDIA) by Boehringer Mannheim, Mannheim, Germany, have been introduced. In addition, Dade Behring improved its enzyme multiplied immunoassay (EMIT) assay. The present study evaluated all 3 new methods in comparison with high-performance liquid chromatography (HPLC) and the FPIA for the TDx analyzer. We measured whole blood cyclosporine concentrations of 179 samples obtained from 127 patients after kidney, bone marrow, heart-lung, and liver transplantation. All 4 automated immunologic methods can be used for routine measurement of cyclosporine whole blood concentrations. Disadvantages, such as higher cross-reactivity (Abbott TDx, CEDIA) or a limited linearity range (EMIT), are accompanied by advantages, such as a high precision (Abbott TDx) or an easy sample handling procedure (CEDIA). Information presented in this article should help to find the most adequate cyclosporine method for each medical laboratory.
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