Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skin biopsy specimens from nine patients with lupus vulgaris were examined in situ by means of monoclonal antibodies directed against phenotypes of lymphocyte subsets, Langerhans cells, HLA-DR antigens, and interleukin 2 receptor. The epidermis showed prominent changes, including intense expression of HLA-DR on keratinocytes, increase in epidermal cell layers, moderate to high Langerhans cell hyperplasia, and infiltration by CD3+ pan-T cells as well as CD8+ (cytotoxic/suppressor) and CD4+ (helper/inducer) T cells. The predominant lymphocyte in the dermal granulomas was the activated CD3+ T cell, expressing major histocompatibility complex class II antigens and interleukin 2 receptor. CD4+ and CD8+ cells were randomly distributed among the epithelioid cells, which showed intense staining for major histocompatibility complex class II antigens. In all except two patients, the CD4+ population was greater than that of the CD8+ cells. CD1+ Langerhans cells were scattered in moderate numbers in the dermal granulomas. Acid-fast bacilli were conspicuously absent in the biopsy specimens. These features suggest that T-cell activation and Langerhans cell hyperplasia are prominent features of dermal tuberculosis.
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PMID:In situ characterization of cellular infiltrates in lupus vulgaris indicates lesional T-cell activation. 168 89

Mice homozygous for the lpr gene spontaneously develop massive lymphoproliferation and an associated lupus-like autoimmune disease. In addition, the total lymphoid organs from these mice express high levels of mRNA for the c-myb proto-oncogene. Since enhanced c-myb mRNA is normally observed in immature thymic lymphocytes but not normal peripheral T cells, this may be indicative of the abnormal maturation state of lpr T lymphocytes. To determine whether the abnormal Lyt-2-, L3T4- (double negative) T lymphocytes in lpr mice express high c-myb, we purified this population by complement-mediated lysis with anti-L3T4 and Lyt-2 antibody from B6/lpr lymph nodes. We found that increased c-myb mRNA is expressed by this double-negative subset. To assess whether the high level of c-myb correlated with the aberrant undifferentiated state of these cells, we examined the effects of T cell differentiation inducers, phorbol ester and calcium ionophore, on c-myb expression. We found that c-myb levels were depressed after phorbol ester and calcium ionophore treatment. Concomitantly, transcriptional activation of the interleukin 2 receptor gene and progression of these cells through the cell cycle were observed. Thus, in B6/lpr double-negative T cells, the regulation of c-myb, interleukin 2 receptor, and cell proliferation may be interrelated. A combination of Northern hybridization and nuclear run-on transcription assays revealed two levels at which c-myb can be regulated in the double-negative T cell subset. The gene is transcriptionally regulated in untreated cells, but on induction with phorbol ester and calcium ionophore, the gene is negatively regulated via post-transcriptional mechanisms.
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PMID:The expression and regulation of c-myb transcription in B6/lpr Lyt-2-, L3T4-T lymphocytes. 311 95

In order to assess the importance of interleukin 2 receptor (IL-2R)-positive activated lymphocytes and macrophages in the pathogenesis of autoimmunity, we tested the prophylactic therapeutic efficacy of an anti-IL-2R (M7/20) monoclonal antibody, which recognizes the 55-kDa subunit of the heterodimeric IL-2R in two distinct models: the nonobese diabetic mouse and the NZB x NZW F1 hybrid with lupus. Treatment with anti-IL-2R monoclonal antibody suppressed autoimmune insulitis in nonobese diabetic mice and lupus nephritis in the NZB x NZW F1 hybrid. These studies indicate that highly selective targeting to activated lymphocytes and macrophages expressing the IL-2R provides a discrete method of dampening autoimmunity.
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PMID:Anti-interleukin 2 receptor antibody suppresses murine diabetic insulitis and lupus nephritis. 312 42

Two TNF binding proteins have been characterized as soluble fragments of TNF receptors. We measured the plasma concentrations of soluble type A (p75) and type B (p55) TNF receptors in patients with systemic lupus erythematodes (SLE), progressive systemic sclerosis (PSS), and mixed connective tissue disease (MCTD). In SLE and PSS patients plasma concentrations of both types of TNF receptors and in MCTD patients type A TNF receptors were significantly elevated compared to controls. Plasma concentrations of both soluble TNF receptors were highly correlated in SLE, PSS, and MCTD patients, indicating a possible coregulation of both TNF receptors. In contrast, soluble interleukin 2 receptor (sCD 25) plasma concentrations were not correlated and seem to be an independent parameter. The soluble forms of the TNF receptors neutralize TNF in cytotoxicity assays and are functionally active as TNF antagonists. In one patient with SLE, autoantibodies against type A TNF receptors were detected, TNF alpha, and TNF beta did not interfere with the autoantibody binding to the receptor.
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PMID:Evaluation of soluble tumor necrosis factor (TNF) receptors and TNF receptor antibodies in patients with systemic lupus erythematodes, progressive systemic sclerosis, and mixed connective tissue disease. 824 78

OBJECTIVES--To investigate urine neopterin as a parameter of disease activity in an unselected group of patients with systemic lupus erythematosus (SLE) and to study the relation between urine neopterin and certain patterns of organ disease and differing drug regimens in the treatment of SLE. METHODS--Neopterin was determined by high performance liquid chromatography in 115 early morning urine samples from 68 patients with SLE. Serum soluble interleukin 2 receptor (sIL-2R) and antibodies to double stranded DNA (dsDNA) were determined by enzyme linked immunosorbent assay (ELISA), and the erythrocyte sedimentation rate (ESR), plasma C3, C4, and C3 degradation products (C3dg) were measured in corresponding blood samples. Disease activity was scored using the British Isles Lupus Assessment Group (BILAG) index. RESULTS--Urine neopterin was significantly increased in patients with active and inactive SLE compared with the control group and was significantly higher in patients with active than in those with inactive SLE. Urine neopterin did not distinguish between subsets of patients with SLE with particular patterns of organ disease, as defined by the BILAG index, nor was its level primarily influenced by differing drug regimens. Levels of serum sIL-2R, antibodies to dsDNA, the ESR, and plasma C3, C4, and C3dg were also significantly different between the patients with active and inactive SLE. Unlike urine neopterin there was considerable overlap in the values of these parameters between the two activity groups. Highly significant correlations found between urine neopterin and serum sIL-2R, ESR, and plasma C3, C4, and C3dg suggest the close association of neopterin with clinical activity in SLE. Multivariate logistic regression analysis showed that urine neopterin > 300 mumol/mol creatinine was a highly significant predictor of disease activity with an odds ratio of 3.51. CONCLUSIONS--Determination of urine neopterin, a non-invasive, relatively simple and inexpensive measurement, appears to be the best parameter for assessing and monitoring disease activity and treatment in patients with SLE.
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PMID:Urine neopterin as a parameter of disease activity in patients with systemic lupus erythematosus: comparisons with serum sIL-2R and antibodies to dsDNA, erythrocyte sedimentation rate, and plasma C3, C4, and C3 degradation products. 832 94