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 isolated hybridoma cells, which secreted monoclonal antibody (MAb) 121 SLE, an IgM showing the following reactivities: (1) by immunodiffusion, MAb 121 SLE and MAb NS 19-9 (a monoclonal antibody directed against a sialylated Lewis(a) antigen called CA 19-9) showed an identical precipitin line with mucin preparation containing this CA 19-9; (2) by immunoradiometric assay, MAb 121 SLE totally inhibited fixation of radiolabelled MAb NS 19-9; (3) by immunoperoxidase, MAb 121 SLE stained the normal gastrointestinal mucosa of Le-positive individuals exclusively, and this staining disappeared after neuraminidase treatment, as observed using MAb NS 19-9. However, the pattern of the staining obtained with MAb 121 SLE differed slightly from that given by MAb 19-9 on the different positive areas of the gastrointestinal mucosae. These differences principally concerned the number of positive epithelial cells and the intensity of their staining; (4) moreover, antibodies against idiotype determinant of NS 19-9 antibody did not react with the antibody 121 SLE. We concluded that MAb 121 SLE is different from the MAb NS 19-9. However, both these antibodies were associated with the same molecular sialylated Lewis(a) structure.
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PMID:Monoclonal antibody against sialylated Lewis(a) antigen. 244 92

The benefit of high-dose, pulse intravenous methylprednisolone (IVMP) for some patients with active lupus nephritis would appear paradoxical, since active nephritis is associated with profound abnormalities in Fc gamma receptor function, and several studies have demonstrated that glucocorticoids decrease monocyte Fc gamma receptor expression and phagocytic function. To resolve this paradox, we investigated the possibility that pulse IVMP might enhance monocyte Fc gamma receptor function in patients with systemic lupus erythematosus (SLE). Circulating immune complex (CIC) levels, Fc gamma receptor-mediated clearance, and Fc gamma receptor-dependent monocyte function were analyzed in 23 SLE patients before and after pulse IVMP (1 gm daily for 3 days). A biphasic response in CIC levels, determined by a staphylococcal protein A binding assay, was observed. Initially, CIC levels increased within 2-4 hours after the first dose of pulse IVMP and then decreased by 50% within 24-48 hours after the completion of therapy. Fc gamma receptor-mediated binding and phagocytosis of IgG-sensitized erythrocytes (EA) by monocytes in vitro were significantly enhanced 24 hours after the final dose of pulse IVMP (pre-IVMP versus post-IVMP 43 +/- 14% versus 53 +/- 12% EA rosettes, P less than 0.01; 3.00 +/- 1.04 versus 3.99 +/- 1.30 EA ingested/monocyte, P less than 0.01). In contrast, there was no change in the phagocytosis of an Fc gamma receptor-independent probe, neuraminidase-treated erythrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High-dose, pulse intravenous methylprednisolone enhances Fc gamma receptor-mediated mononuclear phagocyte function in systemic lupus erythematosus. 252 82

Fc gamma receptor-dependent mononuclear phagocyte system (MPS) clearance of opsonized erythrocytes is prolonged in healthy adults with the class II alloantigens HLA-DR2, DR3, or DQw1, despite normal receptor-specific Fc ligand binding by monocytes in these groups. To investigate the basis for the MPS dysfunction, we determined the phagocytic capacity of blood monocytes from 66 disease-free adults and analyzed the data according to the HLA type of the subjects. The data demonstrate decreased phagocytosis of IgG-sensitized erythrocytes (EA) by monocytes from HLA-DR2, DR3, or DQw1-positive subjects compared with normals without these B cell alloantigens (2.87 +/- 0.83 erythrocytes/monocyte vs 3.87 +/- 1.05, p less than 0.004; 3.01 +/- 0.94 vs 3.87 +/- 1.05, p less than 0.02; 3.18 +/- 0.89 vs 3.87 +/- 1.05, p less than 0.02, respectively). Because HLA-DR2 and DQw1 are in linkage disequilibrium, we compared EA phagocytosis in subjects with DQw1 alone to normals without HLA-DR2, DR3, or DQw1. Among subjects positive only for DQw1, no significant decrease in phagocytosis could be seen (3.46 +/- 0.95 vs 3.87 +/- 1.05, p = NS). To determine whether these differences represented an Fc receptor-specific dysfunction or a more generalized decrease in phagocytic activity, we compared the quantitative phagocytosis of EA with that of neuraminidase-treated erythrocytes (EN), which is Fc receptor independent and beta-glucan receptor mediated. No segregation of phagocytic capacity for EN by HLA class II phenotypes could be demonstrated (DR2, 2.68 +/- 1.30 erythrocytes/monocyte; DR3, 2.95 +/- 1.30; DQw1, 2.84 +/- 1.15; others, 3.06 +/- 1.14). Our data indicate that the decrease in phagocytosis by blood monocytes from normal individuals with HLA-DR2 or DR3, the class II alloantigens associated with systemic lupus erythematosus and other autoimmune diseases, is specific for the Fc receptor-mediated process. This alteration of Fc receptor function among immunogenetically defined individuals may contribute to their predisposition to autoimmune disease. These differences may also apply to other Fc receptor-initiated cellular functions.
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PMID:Altered phagocytosis by monocytes from HLA-DR2 and DR3-positive healthy adults is Fc gamma receptor specific. 300 7

The present study examined the effect of two drugs, which contain either an aromatic amine or hydrazine moiety and are known to induce lupus like syndromes in man (procainamide and hydralazine) and an aliphatic amine (dansylcadaverine), on pokeweed mitogen (PWM)-induced B cell production of immunoglobulin G (IgG). These compounds all inhibited IgG production and generation of IgG plaque forming cells, whereas derivatives of them, without free amine groups, had little or no effect. The compounds inhibited differentiation of B cells to plasma cells, rather than production and secretion of IgG. Mitogen free culture supernatants of peripheral blood mononuclear cells (PBM) activated by the oxidizing mitogen, neuraminidase and galactose oxidase (NAGO), prevented the inhibition of B cell maturation. Moreover, incubation of NAGO treated PBM with hydralazine prevented the production of soluble factors capable of promoting B cell maturation in the presence of hydralazine. We conclude from these studies that procainamide, hydralazine and dansylcadaverine inhibit PWM-induced B cell maturation to plasma cells by an indirect mechanism, via inhibition of production of lymphokines by helper cells. The primary amine or hydrazine group appears to be required for the inhibitory effect, since analogues of the inhibitory compounds, without primary amine groups, are non-inhibitory.
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PMID:Inhibition of pokeweed mitogen-induced B cell differentiation by compounds containing primary amine or hydrazine groups. 388 87

Sera of patients with infectious mononucleosis (IM) and various other diseases were studied for agglutinins against Newcastle disease virus (NDV)-modified human group O red blood cells (NDVO) and antibodies to the NDV preparations. In agreement with previous studies, the NDVO antibodies are found in a wide variety of diseases in addition to IM, including Japanese IM-like syndrome (22%), syphilis (24%), lepromatous leprosy (30%), systemic lupus erythematosus (29%), multiple sclerosis (18%) and cancer (17%); these antibodies were also found in patients with renal allografts (29%). It was also noted that the Victoria (VIC), Roakin and Herts strains, but not B1 strain of NDV are active in the NDVO agglutination, and VIC and Roakin strains, but not B1 strain in the immunodiffusion. Immunodiffusion and enzyme immunoassay with various preparations of the VIC strain revealed that the major antigen(s) of the virus under study is carried by the hemagglutinin-neuraminidase (H-N) glycoproteins. The H-N molecule was also shown to be able to modify human erythrocytes for the agglutination by the pathologic sera.
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PMID:Antibodies to Newcastle disease virus in various human diseases. 392 Jan 52

The platelet binding properties of human monoclonal lupus autoantibodies have been studied. These IgM autoantibodies, produced by human X human hybridomas derived from lymphocytes of patients with systemic lupus erythematosus, are known to bind to single-stranded DNA. Four anti-DNA antibodies that express the dominant 16/6 idiotype--HF2-1/17, HF2-18/2, HF2-1/13b, and HF3-16/6--bound to glutaraldehyde-fixed platelets. In contrast, HF6-21/28, HF9-11/3, and polyclonal IgM bound poorly to platelets. [35S]Methionine was incorporated into HF2-1/17, and the interaction of the intrinsically radiolabeled HF2-1/17 with fixed platelets was evaluated in a solution phase radioimmunoassay. [35S]Methionine HF2-1/17 bound to fixed platelets and could be displaced by equivalent amounts of HF2-1/17, HF2-18/2, HF2-1/13b, and HF3-16/6. HF2-1/17 bound with greater affinity to fresh platelets and to thrombin-activated platelets than to glutaraldehyde-fixed platelets. Single-stranded DNA competed with platelets for the HF2-1/17 combining site. Treatment of fresh platelets with nuclease I, trypsin, chymotrypsin, and neuraminidase did not alter the binding of antibody to the platelet surface. No binding of antibody to phospholipid micelles was observed. Purified IgM autoantibodies did not inhibit platelet aggregation induced with ADP, thrombin, or ristocetin in platelet-rich plasma. These results indicate that the human IgM monoclonal anti-DNA autoantibodies that express the dominant 16/6 idiotype are polyspecific, bind to platelets, and interact with a platelet epitope that does not appear to involve DNA, protein, or sialic acid. These antibodies interact with platelets through the same sites responsible for antibody-DNA binding.
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PMID:Platelet binding properties of monoclonal lupus autoantibodies produced by human hybridomas. 406 19

We have developed a new, specific, and highly sensitive enzyme-linked immunosorbent assay (ELISA) which quantitates activation of the alternative pathway in human serum, plasma, or on the surface of activators. The ELISA detects the third component of complement (C3b), proteolytic fragment of complement Factor B (Bb), and properdin (P) complex or its derivative product, C3b,P. In the method, activator-plasma mixtures, plasma containing an activated alternative pathway, or other samples are added to the wells of microtitration plates precoated with antibody to P. C3b, Bb,P or C3b,P complexes which become bound are quantitated by subsequently added, enzyme-labeled, anti-C3. The resulting hydrolysis of the chromogenic substrate is expressed as nanograms of C3b by reference to a C3 standard curve. In addition to absolute specificity for activation of the pathway because of the nature of the complex detected by the assay, the ELISA is highly sensitive and able to reproducibly detect 10-20 ng/ml of C3b,P complexes in serum. This value corresponds to 0.0015% of the C3 in serum. In a series of studies to validate the parameters of the ELISA, reactivity was found to be dependent on the presence of alternative pathway proteins, the functional integrity of the pathway, and on the presence of magnesium. Sheep erythrocytes were converted to activators by treatment with neuraminidase. By using a variety of activators, the kinetics of activation and the numbers of bound C3b molecules quantitated by the ELISA were very similar to those measured by C3b deposition. The ELISA also detected identical activation kinetics when MgEGTA-serum and a mixture of the purified alternative pathway proteins were used as sources of the pathway. ELISA reaction kinetics also correlated with the restriction index, a measure of alternative pathway-activating ability. These studies cumulatively validate the ELISA as a direct and quantitative assay for alternative pathway activation. The sensitivity of the ELISA has permitted its use to detect direct alternative pathway activation by several viruses. The ELISA has also shown that certain classical pathway activators trigger the amplification loop of the alternative pathway while others do not. In addition, stable ELISA reactive complexes appeared in the supernatant of mixtures of serum with certain, but not other activators. The ability of the ELISA to detect activation which has already occurred and the stability of the reactive complexes permits studies of clinical sera. Normal human sera (20) contained low levels (5-20 ng/ml) of ELISA-reactive complexes. A proportion of sera from individuals with the adult respiratory distress syndrome (9-10), typhoid fever (8-10), malaria (3-5), gram-negative sepsis (9 of 47), acute trauma and shock (6 f 25), and systemic lupus erythematosus (3 of 29) showed elevated levels of complexes reactive in the alternative pathway ELISA. In contrast, nine sera from patients with circulating C3 nephritic factor were not reactive in the ELISA.
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PMID:Development and application of an enzyme-linked immunosorbent assay for the quantitation of alternative complement pathway activation in human serum. 641 67

The effect of normal human serum on in vitro IgE production was studied in an attempt to determine whether IgE-specific suppressor factors are present in the circulation of nonallergic individuals. Sera from 10 nonatopic donors (serum IgE less than 20 I.U./ml) were filtered through Diaflo CF50A membranes (cutoff point 50,000 D) and various dilutions of the IgE-free serum filtrates (less than 150 pg/ml of IgE) were examined for their ability to suppress spontaneous in vitro IgE synthesis by peripheral blood mononuclear cells (PBMC) from patients with hyper-IgE states. Serum filtrates from all 10 nonatopic donors tested suppressed IgE synthesis (mean suppression = 70 +/- 4%). IgE suppression was isotype specific because addition of the serum filtrates to pokeweed mitogen-stimulated normal PBMC or to spontaneously activated B cells from patients with active systemic lupus erythematosus did not suppress IgG or IgM production. The IgE suppressor activity was destroyed by treatment with trypsin but not with neuraminidase or exposure to heat. Substantial suppressor activity bound to IgE-Sepharose but not to a control IgG-Sepharose column. Further evaluation of the IgE-binding serum IgE suppressor factor(s) revealed a marked affinity for peanut agglutinin-Sepharose but minimal binding to lentil lectin-Sepharose. These results suggest that human serum from nonatopic donors contain low molecular weight IgE-binding factors which selectively suppress IgE production but not IgG production. Characterization of ths IgE-binding suppressor factor(s) reveals physicochemical features similar to those previously described for rat T-cell-derived IgE-binding factors with IgE suppressive activity.
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PMID:IgE-specific suppressor factors in normal human serum. 646 88

In this study we were able to confirm the presence of double marker lymphocytes (D cells) in human peripheral blood from normal subjects in addition to patients with SLE and malignant lymphoma. Quantitation of D cells and Null lymphocytes (N cells) in peripheral blood was not feasible via conventional rosette methods. The present combination method, using two indicators, neuraminidase treated sheep red blood cells (nSRBC) and Immunobeads, allows for simultaneous demonstration of T, B, N and D lymphocytes in a simple reproducible manner. The mean percentage of the D cell counts with this method was 1.8% of total lymphocytes from normal donors, 7.0% in patients with SLE, and 29.2% in patients with malignant lymphoma. The simultaneous quantitation of T, B and N cells in these blood samples was compared to the results of conventional methods, i.e. E rosettes for T cells and EAC rosettes for B cells, which gave similar results. This combination method for simultaneous enumeration of human peripheral lymphocyte subpopulations may offer significant advances in the study and diagnosis of various clinical entities.
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PMID:Increased double marker lymphocytes in systemic lupus erythematosus and lymphoproliferative disorders. 697 6

Patients with SLE develop IgM autoantibodies to different isoforms of CD45, the major surface membrane protein tyrosine phosphatase on lymphocytes and other nucleated hemopoietic cells. Because such autoantibodies could have a potential role in the development of immune dysfunction in this disorder, we performed a series of experiments to characterize their antigenic specificity further. Blots of recombinant E. coli fusion proteins encoded by exons 3-7 of the p220 and p180 isoforms were uniformly non-reactive with SLE IgM, suggesting that anti-CD45 autoantibodies in SLE are directed against conformational and/or carbohydrate epitopes, rather than linear polypeptide epitopes. This issue was examined further using chemically and enzymatically modified CD45 purified from T cells by lectin affinity chromatography as substrates. Treatment of CD45 with 25 mM sodium-m-periodate, sufficient to abrogate binding to various lectins, abolished the reactivity with SLE anti-CD45 autoantibodies. On the other hand, digestion of CD45 with neuraminidase enhanced the binding of anti-CD45 autoantibodies from some of the SLE sera. This result probably reflects decreased steric hindrance or charge repulsion because the binding of mouse monoclonal antibodies directed against linear polypeptide epitopes of CD45 was similarly enhanced. Digestion of CD45 with N-glycosidase F had no effect on autoantibody staining. Taken together, these data suggest that IgM anti-CD45 autoantibodies in SLE recognize non-sialylated carbohydrate determinants in the highly O-glycosylated polymorphic domains of CD45.
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PMID:Carbohydrate specificity of IgM autoantibodies to CD45 in systemic lupus erythematosus. 753 98


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