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

The human nonspecific suppressor factor (hNSF), the probable counterpart of the murine monoclonal nonspecific suppressor factor (MNSF), has been isolated from the ascitic fluid of a patient with systemic lupus erythematosus and characterized. hNSF presents an inhibitory activity on the proliferation and IgG production of mitogen stimulated human PBMC. In the present study, we demonstrate that hNSF can be isolated from the supernatants of ConA-activated T cells, but not from CD8-depleted T cells, indicating the CD8+ T cells are the major source of the factor. We also studied the effects of hNSF on purified human B and T cells; hNSF strongly inhibited the proliferation and Ig secretion by highly purified B cells induced by SAC plus IL-2, as well as the proliferation of T cells activated by Con A plus IL-2. These results indicate that hNSF is a CD8+ T cell product with strong antigen-nonspecific immunoregulatory action on both lymphocyte populations.
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PMID:Human nonspecific suppressor factor (hNSF): cell source and effects on T and B lymphocytes. 778 99

We conducted a clinicopathologic study of 79 cases of Kikuchi's disease. Our results confirmed that Kikuchi's disease is a distinctive type of necrotizing lymphadenitis that affects primarily the cervical lymph nodes of young adults and has a self-limited clinical course. However, female predominance was not as striking as heretofore reported. A low, but possible, recurrence rate of 3.3% was documented. Extranodal cutaneous involvement occurred in one patient who had a more severe and protracted clinical course. Classification of the histopathologic changes into three histologic types was proposed: proliferative, necrotizing, and xanthomatous types. These three types differed in certain aspects of their clinical features. Immunohistologic analysis revealed that the predominant cells of the lesions were various types of histiocytes, including the enigmatic plasmacytoid monocytes. A variable number of CD8(+) T cells correlating with the duration of the disease was detected. B cells were nearly absent, and only an insignificant number of OPD4(+) T cells was present. Eight cases studied by the flow cytometric DNA analysis all showed a diploid DNA content. Although the histologic changes of Kikuchi's disease were variable, the findings were sufficiently distinctive to permit accurate diagnosis. Malignant lymphoma and especially lupus lymphadenitis can be mistaken for Kikuchi's disease; thus differentiation is crucial.
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PMID:Kikuchi's disease (histiocytic necrotizing lymphadenitis). A clinicopathologic study of 79 cases with an analysis of histologic subtypes, immunohistology, and DNA ploidy. 779 78

Patients with systemic lupus erythematosus (SLE) have increased percentages of activated T cells and increased numbers of cells with mutations in their hypoxanthineguanine phosphoribosyltransferase (hprt) gene, as judged by growth in the presence of 6-thioguanine. To study the relevance of these mutant T cells to disease pathogenesis, we have assessed the phenotype and functional capabilities of such cells from 21 patients with SLE who never had received cytotoxic drugs. The frequency of T cells with mutations in hprt in the blood of these patients ranged from normal to 25 times normal (mean +/- SEM [21.1 +/- 6.1] x 10(-6) versus [4.8 +/- 0.8] x 10(-6), in 15 age-matched normal individuals, P < 0.001) and correlated significantly with disease duration. CD4+ and CD8+ phenotypes were comparable among mutated and nonmutated clones from both patients and normals. Although the frequency of CD3+CD4-CD8- cells was low, it was increased among SLE-derived T cells (mutated and wild-type) compared with clones derived from normals (5% for SLE vs 1% for normals). A substantial percentage of all clones were able to help autologous B cells to produce anti-ssDNA, 11 of 68 (16%) selected clones and 3 of 28 (11%) nonselected clones. Help for autoantibody production was confined to CD4+ SLE-derived T cell clones. It could be blocked using an anti-HLA-DR mAb, suggesting that classical cognate help was operative. This represents the first estimate of the frequency of T cells able to drive autoantibody production in SLE.
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PMID:Characterization of in vivo mutated T cell clones from patients with systemic lupus erythematosus. 782 67

Mice homozygous for the autosomal recessive gene lpr develop marked lymphadenopathy and a systemic autoimmune disease resembling human systemic lupus erythematosus. The enlarged nodes are dominated by T cells with an unusual surface phenotype: dull Thy-1+, dull CD3+, CD4-, CD8-, B220+ (double-negative T cells or DNTs). Despite their massive accumulation in vivo, these cells fail to proliferate in response to conventional T-cell mitogens in vitro. The identification of the lpr mutation as a defect in the Fas apoptosis receptor gene suggests that DNT accumulation may result from abnormal persistence rather than overproliferation. To test in vivo whether DNTs persist abnormally or have a capacity to differentiate into single-positive T cells, we have performed cell transfer experiments between congenic strains of lpr and +/+ mice differentially marked by expression of the Ly-1 or Thy-1 alleles. Although transferred lpr lymph node cells were mostly DNTs at the time of injection, most recovered cells of donor origin were single positive, particularly CD8+, at all time points after transfer. Furthermore, transfer of purified DNTs resulted in recovery of relatively few cells of donor origin. Transfer of lpr T cells enriched for CD8 expression confirmed the preferential survival of this subset. Thus, DNTs are a surprisingly transient population and have little capacity for transformation to single positives. This would suggest that DNTs are constantly being renewed, perhaps from CD4+ and CD8+ precursors.
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PMID:The abnormal lpr double-negative T cell fails to proliferate in vivo. 782 72

Cell surface carbohydrate antigens have been implicated in cell differentiation and maturation and may play a role in immunoregulation. The expression of carbohydrates in peripheral blood lymphocytes (PBL) was studied by double immunofluorescence flow cytometry, using MoAbs CT1 and CT2 but only a small proportion of cells bound these MoAbs. MoAbs CT1, CT2 and the lectin vicia villosa (VV) which share specificity for Gal NAc were then used to examine lymphocytes from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Behcet's disease (BD) and IgA nephropathy. A significant increase in MoAbs CT1 CT2 and VV binding CD4 or CD8 cells was found only with lymphocytes from patients with SLE. However, MoAbs CT or VV binding lymphocytes from healthy subjects were significantly up-regulated by activation with a mitogen (PHA), cross-linked anti-CD3 MoAb or a common antigen (65kDa heat shock protein), suggesting that an increased proportion of T cells expressing these carbohydrates results from any of the three types of lymphocyte activating agents. Inhibition studies were then carried out to determine the relationship between the MoAbs CT1 and CT2, VV and GalNAc. Indeed, VV binding to T cells was significantly inhibited by either MoAbs CT1 or CT2, or GalNAc but not GlucNAc, suggesting that VV shares a common binding site with MoAb CT and that GalNAc may constitute one of the sugar receptors. Investigations of lymphocytes from adult peripheral blood in health and disease suggest that carbohydrate antigens may play a role in activation and immunoregulation.
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PMID:The expression of carbohydrate antigens in activated T cells and in autoimmune diseases. 799 53

To evaluate the role of V beta 8+ T cells in the development of lupus-like autoimmune syndrome in MRL-lpr/lpr mice, we treated them with the F23.1 anti-V beta 8 monoclonal antibody (mAb) from birth to 4 months of age. Here we report that almost complete depletion of V beta 8+ T cells by the F23.1 mAb treatment neither inhibited nor delayed the development of hypergammaglobulinemia, autoantibody production and autoimmune glomerulonephritis in MRL-lpr/lpr mice. In addition, the F23.1 mAb treatment did not prevent the development of lymphadenopathy and the generation of a CD4-CD8- double-negative T cell subset, characteristically accumulating in lpr lymph nodes. Our results strongly argue against the idea that the V beta 8+ T cells play a critical role in the development of lupus-like autoimmune syndrome in MRL-lpr/lpr mice.
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PMID:Lack of association of V beta 8+ T cells with lupus-like syndrome in MRL-lpr/lpr mice. 802 33

An open clinical trial was designed to examine the efficacy and safety of lobenzarit (CCA), a newly developed disease modifying anti-rheumatic drug, in combination with conventional treatment with prednisolone for patients with systemic lupus erythematosus (SLE). Fifteen patients with SLE were given CCA 40 mg b.i.d. for the first 2 weeks, 80 mg b.i.d. for the next 4 weeks, and 80 mg t.i.d. or b.i.d. until the end of the 12-month trial, in addition to prednisolone, whose doses were kept unchanged throughout the trial. The patients' clinical responses to CCA, including alterations in various laboratory parameters and the development of complications, were evaluated at the end of 12 months. Fourteen of the 15 patients completed the 12-month trial. Significant increases in the white blood cell count and CD4/CD8 ratio, as well as decreases in serum anti-DNA antibody, were noted after the trial. Five patients presented with adverse effects, including mild liver dysfunction, gastrointestinal symptoms and dizziness. Only one patient who developed dizziness withdrew at 9 months. Eleven patients could be reevaluated after discontinuation of CCA, and only 2 of them have experienced recurrence of active disease 6 months after discontinuation. In one additional patient who had not responded to prednisolone 35 mg daily, administration of CCA resulted in improvement of the disease activity. These results indicate that CCA in combination with corticosteroids is a useful adjunct in the treatment of SLE. A placebo-controlled study will be necessary to confirm these results.
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PMID:Treatment of systemic lupus erythematosus with lobenzarit: an open clinical trial. 807 Jan 58

Endogenously activated CD8+ cells contribute to the aberrant immune regulation that characterizes SLE. Because stimulation of CD8+ cells with lectin/Ag triggers release of CD8-alpha molecules (sCD8), we measured, in patients with SLE, serum sCD8 content, its correlation with disease activity, and the in vitro release of sCD8 by SLE PBMCs. sCD8 levels, measured by ELISA in sera of 50 SLE patients, were higher than normal in 16 out of 21 mildly active and 15 out of 15 active SLE patients. sCD8 correlated positively with the clinical index for disease activity (r = 0.57, p = 0.001) and with sIL-2R levels (r = 0.52, p < 0.0001), and negatively with serum C3 levels (r = -0.5, p < 0.04). Freshly isolated SLE PBMCs had higher than normal CD8-alpha mRNA levels and secreted high levels of sCD8 in vitro (p < 0.05 vs control PBMC). sCD8 in vitro release by SLE PBMCs may be modulated by non-CD8+ cells. Thus, anti-CD2 mAb inhibited sCD8 release, whereas anti-HLA mAb increased it in unseparated PBMCs, but not in CD8+ enriched cultures. Moreover, sCD8 release increased significantly in PBMC cultures enriched for CD8+ DR+ cells by negative selection. Added-back monocytes decreased sCD8 to original levels, but not after glutaraldehyde fixation, nor in the presence of anti-HLA mAb. Further, lectin-induced IgG production and proliferation were reduced in the presence of sCD8, suggesting that the soluble CD8 molecules may be immunoregulatory. Because the high sCD8 levels in sera of active SLE likely reflect pathogenic cell activation, serum CD8 content may be an additional serologic activity marker, and its study could provide insights into mechanisms of disease.
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PMID:Elevated in vivo and in vitro secretion of CD8-alpha molecules in patients with systemic lupus erythematosus. 814 10

MRL/Mp-lpr/lpr (MRL-lpr) mice have been used for a model of human systemic lupus erythematosus. This strain of mice homozygous for an autosomal recessive mutation, lpr (lymphoproliferation), develops massive lymphadenopathy with the expansion of CD4-CD8- (double negative; DN) T cells. Recently it was demonstrated that lpr mice have defects in the gene of Fas antigen which mediates apoptosis, indicating a possibility of defect in negative selection of autoreactive T cells in the thymus of lpr mice. However, the mechanisms that control the accumulation of DN T cells in lymph nodes, and the involvement of DN T cells in the clinical manifestation of disease, have not been well understood. In this study, the expression of various cell adhesion molecules on lymphocytes from MRL-lpr mice was examined. The strong expression of CD44 antigen as well as heat stable antigen (HSA) on abnormal DN T cells of lymph nodes was characteristic in MRL-lpr mice. Furthermore, the accumulation of DN T cells in lymph nodes might result from augmented binding of lymphocytes to endothelial cell surface of lymph nodes, possibly due to the failure of Mel-14 antigen shedding from DN T cell surface. In addition, it was found that monoclonal antibodies reactive with cell adhesion molecules such as CD44, Mel-14, CD45R and HSA expressed on DN T cells, could trigger the lytic activity of DN T cells and redirected DN T cell-mediated lysis of Fc-receptor-positive target cells (EL-4). In contrast to T cell receptor (TCR)-mediated cytotoxicity, this redirected cytotoxicity was not inhibited by anti-lymphocyte function associated antigen-1 (LFA-1) antibody. Thus, cell adhesion molecules may play a major role in delivering the transmembrane signal to DN T cells of MRL-lpr mice that trigger the lytic activity. It is likely that DN T cells of MRL-lpr mice induce tissue damages by the interaction with ligand on vascular endothelium or extracellular matrix in vivo.
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PMID:[Functional studies of adhesion molecules on CD4-CD8- double negative T cells of autoimmune MRL/Mp-lpr/mice]. 822 81

Different glucocorticoid preparations modify the immune reaction in different ways. In this paper, the therapeutic efficacy of two glucocorticoids, deflazacort (DFZ) and prednisone (PDN), are discussed in relation to a group of 30 patients with systemic lupus erythematosus (n = 12) or rheumatoid arthritis (n = 18). The disease sub-groups were divided into two arms, one of which was treated with DFZ and one with PDN in a double-blind protocol. The results of this study indicate that DFZ and PDN induced a clinical remission within 1 month which was maintained until the 6th month. Nevertheless, certain immunological modifications, including a significant reduction of the circulating T lymphocyte level and of the CD4/CD8 ratio, which was between 1 and 1,5 during the DFC treatment and between 1 and 2 during the PDN treatment, are more pronounced and more stable with DFZ than with PDN. Moreover, DFZ has a smaller effect on calcium and glucose metabolism than PDN since the serum glucose and calcium level of patients treated with PDN increased respectively from 90 up to 130 mg/dl and from 9,5 to 11,5 mg/dl whereas those of patients treated with DFC remained within the normal range. These findings indicate that DFZ may have advantages over PDN in the treatment of immune-mediated diseases.
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PMID:Comparison of two glucocorticoid preparations (deflazacort and prednisone) in the treatment of immune-mediated diseases. 831 31


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