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)

We conducted a longitudinal evaluation of a patient with systemic lupus erythematosus who constitutively exhibited elevated levels of circulating alpha-interferon (alpha-IFN). This study demonstrated that the serum levels of an activity that renders the endogenous alpha-IFN acid labile are positively correlated with disease activity. This IFN acid lability-inducing activity can also be found in the sera of systemic lupus erythematosus patients who have active disease but who do not have circulating alpha-IFN.
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PMID:Serum activity that confers acid lability to alpha-interferon in systemic lupus erythematosus: its association with disease activity and its independence from circulating alpha-interferon. 232 34

We examined the ability of peripheral mononuclear cells (MNC) from patients with systemic lupus erythematosus (SLE) to produce gamma-interferon (gamma-IFN) in vitro. MNC from patients with SLE produced varying amounts of gamma-IFN upon mitogenic stimulation. However, they produced distinctly decreased amounts of gamma-IFN upon in vitro stimulation with interleukin-2 (IL-2). Deficient production seemed to be primary, rather than secondary to either excessive monocytic suppression or failure of IL-2 to bind to the MNC surface membranes. gamma-IFN-specific RNA transcription, as determined by slot-blot analysis, was severely decreased in MNC that had been stimulated with phytohemagglutinin or IL-2. These findings suggest that MNC of patients with SLE have defects in the IL-2 signal transduction which is required for production of gamma-IFN.
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PMID:Deficient gamma-interferon production in patients with systemic lupus erythematosus. 242 72

Macrophage (MO) and natural killer (NK) cell mediated cytotoxicity to K562 target cells were strikingly decreased in patients with systemic lupus erythematosus (SLE). SLE NK cells failed to release soluble factor(s) for lysing the targets. IFN-induced enhancement of both types of cytotoxicity was impaired. NK cells from healthy subjects kept their activity in culture with or without IFN for more than six days whereas SLE NK cell activity declined to zero at day 3. So, the increased IFN level of many SLE patients and a possible prior IFN priming effect seemed unrelated to the insensitivity to exogenous IFN in vitro. Inhibition factor(s) of SLE serum suppressed NK cytotoxicity in the presence of IFN whereas IFN sensitivity of MO remained unaffected indicating the complex regulation by serum components of immune reactions.
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PMID:Abnormal macrophages and NK cell cytotoxicity in human systemic lupus erythematosus and the role of interferon and serum factors. 248 2

A 39-year-old woman developed transient erythema and arthralgia in spring 1987. In June she had a tick bite followed by local erythema and later migrating skin changes. Furthermore she developed pain in various joints with Raynaud's phenomenon at the fingers, swelling of the knee joints and shoulder pain. Demonstration of antibodies against B. burgdorferi antigen was shown in one institution (IFL, Western blot) while the same serum in two other institutions remained negative (IHA, ELISA). Antibiotic treatment was only temporarily successful. While the demonstration of antinuclear factors could be attributed to cross-reacting antibodies in borreliosis failing effects of absorption of serum with this antigen led to the assumption SLE as the underlying disease. Further indications were lymphopenia, increasing titers of anti ds-DNA antibodies and renal involvement as erythrocyturia and proteinuria. Sudden relief of the symptoms after treatment with steroids may be taken as further prove for this assumption. The interference of both diseases and their similarity in symptoms may impede correct diagnosis.
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PMID:[Borrelia infection and systemic lupus erythematosus]. 269 42

The physicochemical properties of apparently acid-labile IFN-alpha from patients with SLE have been studied. The antigenicity, apparent molecular size, and isoelectric point of SLE IFN-alpha are indistinguishable from those of conventional, previously characterized, acid-stable subspecies of IFN-alpha. However, after partial purification by anion-exchange chromatography, SLE IFN-alpha no longer exhibits acid lability, suggesting that other plasma factor(s) are responsible for the acid lability of SLE IFN-alpha. Addition of SLE plasma, but not normal plasma, to conventional acid-stable IFN-alpha renders the exogenous IFN-alpha acid labile. Preliminary results demonstrate that an acid-dependent IFN-inactivating activity can be partially purified from SLE plasma by anion-exchange chromatography.
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PMID:Interferon alpha associated with systemic lupus erythematosus is not intrinsically acid labile. 292 26

By using the OKM1 monoclonal antibody and the fluorescence-activated cell sorter to identify lymphocytes bearing iC3b (type 3) complement receptors, two principal populations of OKM1+ lymphocytes have been identified in human peripheral blood. One subset exhibited azurophilic granules and Fc receptors for IgG stained by Leu-11. The other population did not display FcR, but was enriched in cells reacting with OKT3 and OKT8 (low intensity). In healthy subjects, approximately 60% of CR3+ lymphocytes were granular FcR-bearing cells and only 18% co-expressed OKT3 determinants. In patients with systemic lupus erythematosus (SLE), CR3+ lymphocytes were predominantly FcR negative cells and 71% lacked granules. Only 33% reacted with Leu-11, but 50% co-expressed OKT3, 44% reacted with OKT8+, and 15% were OKT4+. We tested the hypothesis that agranular OKT3+ Leu-11- lymphocytes, such as those found in SLE patients, contained the precursors of natural killer (NK) cells. Leu-11+ cells were removed from normal lymphocytes by complement lysis, and the remaining cells were treated with recombinant IFN-alpha, IFN-gamma, or IL 2. These procedures were ineffective in generating typical NK effector cells. Our studies do not support the hypothesis that CR3+ Leu-11- lymphocytes are the precursors of granular Leu-11+ NK cells.
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PMID:Studies on human blood lymphocytes with iC3b (type 3) complement receptors. I. Granular, Fc-IgG receptor positive and negative subsets in healthy subjects and patients with systemic lupus erythematosus. 293 74

During autologous mixed lymphocyte reaction (AMLR) both helper and suppressor T cells capable of regulating B cell responses are generated. The proliferative response of T cells as well as the generation of T suppressor cells in the AMLR of patients with active systemic lupus erythematosus (SLE) is diminished. In contrast, the T helper cells generated in the AMLR show a hyperactivity. The diminished HLA-class II antigen expression observed on non-T cells of SLE origin was restored by treatment of the cells with gamma-interferon (gamma-IFN). When tested by immunoglobulin secretion, gamma-IFN enhanced T helper cell activity but failed to affect T cell proliferation and T suppressor cell generation in the AMLR derived from patients with SLE. Human recombinant interleukin 2 restores both the proliferative response of T cells and the induction of T suppressor cells in AMLR.
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PMID:IL-2 normalizes defective suppressor T cell function of patients with systemic lupus erythematosus in vitro. 295 81

Human alpha interferons (IFN-a) cause a reorganization of internal cell membranes into tubuloreticular inclusions (TRI). Morphogenesis and cytochemistry indicate a pre-Golgi intracisternal origin from the endoplasmic reticulum. Clinically, TRI formation in human blood mononuclear cells correlates with systemic IFN-a treatment or with endogenous overproduction of IFN-a in viral or autoimmune diseases (e.g., rubella syndrome, AIDS, systemic lupus erythematosus). In vitro, TRI formation can be produced by treatment of Daudi lymphoblasts or vascular endothelial cells with IFN-a, and is blocked by actinomycin-D. In Daudi lymphoblasts or vascular endothelial cell cultures, TRI formation parallels induction of 2'-5' A synthetase, inhibition of thymidine kinase and growth inhibition; however, heavy water treatment of Daudi cells prevented TRI formation while induction of 2'-5' A synthetase and growth inhibition persisted. TRI formation was dissociated from IFN-a antiproliferative activity in a mutant clone of Daudi lymphoblasts. Decreased glycoprotein biosynthesis and increased phospholipid biosynthesis may accompany progressive TRI accumulation.
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PMID:Tubuloreticular reorganization of cytomembranes in cells treated with human alpha interferons--a review. 307 Jul 35

The (NZB X NZW)F1 mouse is recognized as an important animal model of the human disease systemic lupus erythematosus (SLE). Groups of NZB/W F1 mice were treated either with IFN-gamma or with PBS. The results demonstrate that IFN-treated animals have accelerated development of fatal immune complex glomerulonephritis relative to age-matched controls. On the other hand, administration of mAbs specific for IFN-gamma to such mice from 4 to 7 mo of age resulted in significant remission. Development of both proteinuria and anti-DNA antibodies were delayed and survival at 11 mo was increased from less than 20% to 95% in treated mice relative to controls (p less than or equal to 0.001). These findings may have therapeutic implications for the treatment of SLE.
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PMID:In vivo treatment of (NZB X NZW)F1 lupus-like nephritis with monoclonal antibody to gamma interferon. 311 9

Attempts to detect immune mediators in RA synovial fluids by bioassay or radioimmunoassay have yielded conflicting results, and so we have begun to analyse the complex immunological reactions occurring within the rheumatoid joint using recombinant DNA technology. High levels of Interleukin-2 (IL-2) and IL-2 receptor transcripts were found in the mononuclear cells of the rheumatoid lesions. Interferon gamma (IFN gamma) mRNA was also detected, although at lower level than IL-2. To investigate the possible relevance of IL-2 and IL-2 receptor mRNA expression to the chronicity of the disease, RA joint cells were cultured in the absence of any stimulus, and the duration of mRNA expression compared to that of blood mononuclear cells (PBM), optimally stimulated. IL-2 mRNA was found to persist in culture for many days, in contrast to its transient (less than 24 h) presence in stimulated PBM. IL-2 receptor expression was also prolonged. In contrast IFN gamma mRNA, present at biopsy in 10/12 RA samples, was found to increase significantly in vitro. These results suggest that persistent T cell activation is of importance in the pathogenesis of RA, and suggests that prolonged mediator production (IL-2 and IFN gamma) may be of importance. The elevation of IFN gamma mRNA in culture and its lower relative expression suggests that there are inhibitory immunoregulatory influences within the RA joint. To determine whether abnormal IL-2 mRNA expression may be due to a genetic defect in the region controlling IL-2 gene expression, Southern blotting analysis of genomic DNA was performed with a 5' flanking probe using normal, RA and systemic lupus erythematosis patients. No abnormalities were detected.
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PMID:Detection of activated T cell products in the rheumatoid joint using cDNA probes to Interleukin-2 (IL-2) IL-2 receptor and IFN-gamma. 312 92


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