Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In clinically quiescent SLE hypergammaglobulinaemia, presence of autoantibodies, and increased soluble IL-2 receptors (sIL-2R) have been reported, suggesting persistent B as well as T cell activation. In contrast, the primary immune response to test antigens is markedly decreased. To analyse these phenomena at a cellular level, we undertook a cross-sectional study on 13 non-active SLE patients and 15 controls. We determined the composition of lymphocyte subsets with special attention to activation markers (CD25, HLA-DR, CD38) and the presence of naive T cells (CD45RO-), and related those findings to serological parameters. In non-active SLE patients the expression of activation markers on B cells and T cells was higher than in normal controls (P < or = 0.02), but was not interrelated. Percentages of activated B cells in SLE were related to levels of total IgG (P < 0.02) and IgM (P < 0.02) but not to anti-dsDNA, suggesting a disordered immune system also in clinically quiescent SLE. Numbers of CD4+ cells (P < 0.001) and CD4+CD45RO- cells (P < 0.05) were decreased. The latter finding might explain the anergy to primary test antigens in clinically quiescent SLE.
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PMID:B cell activation in clinically quiescent systemic lupus erythematosus (SLE) is related to immunoglobulin levels, but not to levels of anti-dsDNA, nor to concurrent T cell activation. 810 Jul 46

In the peripheral blood (PB) we detected so-called early plasma cells that might already be committed to entering the bone marrow (BM). By two-colour staining with FITC-anti-CD38 antibody, their intensity (CD38++) of expression of CD38 antigen was between that of germinal centre (GC) B cells (low expression (CD38+)) and that of BM plasma cells (high expression (CD38++)), and their phenotype was CD38++ CD19+ CD10- CD20- CD21+ CD24- CD39+ CD5- VLA-4+ VLA-5- MPC-1- without expression of surface membrane IgM (SmIgM). Morphological and immunological examination of the sorted cells confirmed that they were plasmacytoid cells with expression of cytoplasmic IgG (cIgG). Variations of these early plasma cells were examined in various diseases. In active systemic lupus erythematosus, bacterial septicaemia and liver cirrhosis, early plasma cell levels were significantly increased in PB, and after subsidence of such inflammation (inactive states) these cells returned to normal levels. In contrast, normal early plasma cells were significantly suppressed in myelomas, whilst normal or slightly increased numbers of early plasma cells was found in benign monoclonal gammopathy (BMG). In addition, the number of normal early plasma cells returned to a normal level in myeloma cases with complete responses. Therefore, early plasma cells were identified phenotypically, and an increase and decrease in these cells in PB may reflect mobilization and suppression, respectively, of activated B cells into BM plasma cells.
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PMID:Identification of early plasma cells in peripheral blood and their clinical significance. 856 94

The objective was to serially analyse T and B cell activation in relation to autoantibody production during the development of relapses in SLE. In a prospective study we serially analysed, by flow cytometry, T cell activation in relation to B cell activation and anti-dsDNA production in quiescent SLE and during the development of a clinical relapse. In addition, we related changes in T and B cell activation to changes in levels of anti-dsDNA and total IgG. During periods with clinically quiescent disease, the expression of activation markers on T cells (IL-2R and HLA-DR) and B cells (CD38) was persistently higher in SLE than in healthy controls (P < 0.001). Percentages of CD20+ CD38+ B cells were related to levels of total IgG (P < 0.02), but not to levels of anti-dsDNA. Development of disease activity was paralleled by an increase in the percentages of CD4+ T cells (P < 0.005) and CD20+ CD38+ B cells (P < 0.001), which were interrelated. Increases in B cell activation were related to increases in levels of anti-dsDNA (P < 0.005), but not to changes in total IgG levels. B cells expressing high levels of CD38 spontaneously produced IgG class anti-dsDNA in vitro. Persistence of activated B cells during periods with clinically quiescent disease in SLE seems to underly hypergammaglobulinaemia but not anti-dsDNA production. Prior to clinical disease activity, further activation of T and B cells occurs, which is paralleled by rises of anti-dsDNA but not of total IgG. This suggests that the production of anti-dsDNA is a T cell-dependent antigen-driven process, which is independent of the polyclonal activation of the immune system inherent to the disease.
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PMID:Anti-dsDNA production coincides with concurrent B and T cell activation during development of active disease in systemic lupus erythematosus (SLE). 909 29

We have previously shown that patients with SLE have significantly lower percentages and absolute numbers of NK(CD3-/CD16+56) cells in their peripheral blood compared with normals. Patients with active disease had very low levels of NK cells and the reduction was also associated with patients who had renal involvement. We have now performed a serial study immunophenotyping 11 patients with SLE and renal involvement using dual colour immunofluorescence and flow cytometry. Patients were tested every three months on an average of three occasions. As a control, nine SLE patients without renal involvement were immunophenotyped for similar intervals; 11 normal controls were also tested. Major lymphocyte subsets (T, B and NK) remained very stable during serial bleeds. However, the NK cell populations were decreased significantly in patients with renal involvement both as percentages (5 +/- 6 vs 9 +/- 5, P < 0.0001) and absolute counts (75 +/- 108 vs 109 +/- 52, P < 0.001) in comparison to non-renal patients. Analysis of disease activity using BILAG score showed an inverse correlation between renal system activity and percentage and absolute number of NK cells (P < 0.002 and 0.01, respectively). In this study we have also analysed a CD8 T cell subset which we have not studied before. We have found a significantly increased percentage of CD38+CD8+ T cells(activated CD8 subset) in patients with SLE in comparison to normal controls. We did not find any association with the CD38+CD8+ T cells and disease activity as measured by BILAG or renal involvement. NK cells are important factors in immunity against virus infections and tumour cells. CD38+CD8+T cells are increased in viral infections. We speculate that the lack of NK cells in SLE patients might have an association with increased CD38 expression.
Lupus 1997
PMID:Lack of NK cells in lupus patients with renal involvement. 941 85

Cells spontaneously secreting IgG or IgM (ISC) are present at a high level in the blood of patients with systemic lupus erythematosus (SLE). By use of magnetic-bead techniques, mononuclear cells from such patients and healthy donors were fractionated according to expression of CD19 or CD38 and the cell fractions were then cultured in the absence of added mitogen/antigen for 5/6 days. Supernatant IgG and IgM were determined and, in addition, in the CD38 experiments ISC were enumerated both before and after culture. Much of the immunoglobulin-producing capacity of unfractionated cells (UFC) from both donor groups was recovered in the CD19- fraction, and no immunoglobulin was produced by CD19+ cells suggesting, unexpectedly, that ISC were not expressing CD19. By contrast, CD38 fractionation resulted in nearly all ISC passing to the CD38+ fraction which produced levels of immunoglobulin approaching 50% that of UFC. On culture of CD38- cells there was a build up in the number of IgG and IgM ISC, this being particularly striking in the controls with numbers well in excess of those in UFC. Not all these new ISC became CD38+, but the maturation process was more efficient in the SLE patients. The possibility is discussed that the spontaneous response in the CD38- populations is due to removal of CD38+ natural killer (NK) cells. Removal of ISC that are present preculture is a helpful initial step in studying ISC generation in the disease.
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PMID:Spontaneous immunoglobulin-producing capacity of cultures from lupus patients and normal donors following depletion of cells expressing CD19 or CD38. 952 7

Systemic lupus erythematosus (SLE) is characterized by generalized immune activation. Part of this might be explained by a decreased rate of apoptosis, possibly related to elevated levels of soluble Fas (sFas) which can inhibit Fas mediated apoptosis of lymphocytes. In order to substantiate the relation between levels of sFas and lymphocyte activation in SLE we monitored sFas levels, lymphocyte activation and disease activity in 25 SLE patients. SLEDAI scores were registered and sera were assayed for sFas levels by an enzyme-linked immunosorbent assay. Flow cytometry was used to monitor the state of activation of lymphocyte subsets. Eighteen healthy, age-matched volunteers served as controls. Soluble Fas levels were elevated in SLE patients (n=25) compared to healthy controls (n=18, P=0.002). Soluble Fas levels correlated with SLEDAI scores (r=0.45, P=0.02). Levels of sFas correlated with the percentages of activated B cells defined as CD20(+)CD38(+) cells (r=0.47, P=0.009). Percentages of CD20(+)CD38(+) cells were increased in quiescent SLE compared to healthy controls (P=0.003). The expression of activation markers on CD4(+) T lymphocytes (IL-2R, P=0.04; HLA-DR, P=0.01) and CD8(+) T lymphocytes (HLA-DR, P=0.007) was also increased in quiescent SLE compared to controls. Activation markers on all lymphocyte subsets tended to increase further during disease activity. No correlation was observed between percentages of activated T lymphocyte subsets and levels of sFas. In conclusion, soluble Fas levels are increased in SLE patients and correlate with disease activity as measured by the SLEDAI score and B and T cell subsets are activated even during quiescent SLE. Serum levels of sFas correlate with percentages of activated B cells but not with that of activated T cells.
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PMID:Do elevated levels of serum-soluble fas contribute to the persistence of activated lymphocytes in systemic lupus erythematosus? 980 29

In patients with active systemic lupus erythematosus (SLE), a marked B lymphocytopenia was identified that affected CD19(+)/CD27(-) naive B cells more than CD19(+)/CD27(+) memory B cells, leading to a relative predominance of CD27-expressing peripheral B cells. CD27(high)/CD38(+)/CD19(dim)/surface Ig(low)/CD20(-)/CD138(+) plasma cells were found at high frequencies in active but not inactive SLE patients. Upon immunosuppressive therapy, CD27(high) plasma cells and naive CD27(-) B cells were markedly decreased in the peripheral blood. Mutational analysis of V gene rearrangements of individual B cells confirmed that CD27(+) B cells coexpressing IgD were memory B cells preferentially using V(H)3 family members with multiple somatic mutations. CD27(high) plasma cells showed a similar degree of somatic hypermutation, but preferentially employed V(H)4 family members. These results indicate that there are profound abnormalities in the various B cell compartments in SLE that respond differently to immunosuppressive therapy.
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PMID:Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus. 1106 60

We have analyzed the blood B cell subpopulations of children with systemic lupus erythematosus (SLE) and healthy controls. We found that the normal recirculating mature B cell pool is composed of four subsets: conventional naive and memory B cells, a novel B cell subset with pregerminal center phenotype (IgD(+)CD38(+)centerin(+)), and a plasma cell precursor subset (CD20(-)CD19(+/low)CD27(+/++) CD38(++)). In SLE patients, naive and memory B cells (CD20(+)CD38(-)) are approximately 90% reduced, whereas oligoclonal plasma cell precursors are 3-fold expanded, independently of disease activity and modality of therapy. Pregerminal center cells in SLE are decreased to a lesser extent than conventional B cells, and therefore represent the predominant blood B cell subset in a number of patients. Thus, SLE is associated with major blood B cell subset alterations.
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PMID:Increased frequency of pre-germinal center B cells and plasma cell precursors in the blood of children with systemic lupus erythematosus. 1149 26

The changes in bone marrow (BM) stem cell reserve and function and stromal cell function in patients with active systemic lupus erythematosus (SLE) were investigated. The study was carried out on seven SLE patients and 28 healthy controls using flow cytometry and in vitro cell culture assays. We found that patients had low CD34(+) cells, compared with the control group, reflecting the decrease of both CD34(+)/CD38(-) and CD34(+)/CD38(+) cells. Patient CD34(+)/Fas(+) but not CD34(-)/Fas(+) cells were significantly increased. Apoptotic (7AAD(dim)) cells were higher among CD34(+)/Fas(+) than among CD34(+)/Fas(-) cells, and individual values of apoptotic CD34+ cells strongly correlated with the number of CD34(+)/Fas(+) cells. These findings are suggestive of a Fas-mediated apoptosis accounting for the low CD34(+) cells in SLE patients. Moreover, we found that patients had low numbers of granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E), compared with the control group, and that the generation of colony-forming cells in long-term BM cultures was significantly reduced. Patient BM stroma failed to support allogeneic progenitor cell growth. In one patient, CD34(+) cells were increased, apoptotic CD34(+)/Fas(+) cells were normalized and defective stromal cell function was restored after autologous stem cell transplantation. We concluded that defective haemopoiesis in SLE patients is probably caused, at least in part, to the presence of autoreactive lymphocytes in BM.
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PMID:Increased apoptosis of bone marrow CD34(+) cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus. 1172 30

Levels of apoptotic lymphocytes have been found to be increased in SLE and persistence of apoptotic cells has been associated with autoantibody production. Increased lymphocyte Fas (CD95) expression due to lymphocyte activation may account for increased susceptibility to Fas-mediated apoptosis in SLE. Flowcytometry was performed to evaluate membrane expression of Fas in combination with the activation markers CD25, HLA-DR and CD38 on, respectively, CD4+, CD8+ and CD19+ lymphocytes of SLE patients with inactive (n = 20) and with active disease (n = 13). SLEDAI-scores were calculated. Healthy volunteers (n = 14) served as controls. Percentages of CD4+ T-cells expressing CD25 and CD19+ B-cells expressing CD38 were increased in patients with active disease compared to controls (P = 0.03, P = 0.04, respectively). In contrast to CD4+ and CD8+ cells, percentages of CD19+ cells expressing Fas were increased in SLE patients with active disease (P = 0.0002 vs controls). In these patients percentages of cells double positive for both CD38 and Fas were increased compared to patients with inactive disease (P = 0.006) and controls (P = 0.0007). Percentages of CD19+ cells expressing Fas correlated with SLEDAI-scores. In SLE patients, percentages of Fas-expressing B-lymphocytes are increased, are related to the state of lymphocyte activation, and correlate to disease activity. Increased Fas expression results in a higher susceptibility for Fas-mediated apoptosis, which might contribute to the increased levels of apoptotic lymphocytes in SLE patients.
Lupus 2001
PMID:Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE): relation to lymphocyte activation and disease activity. 1178 76


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