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 expression of Fc gamma RI, Fc gamma RII and Fc gamma RIII on granulocytes in the blood of patients with systemic lupus erythematosus was investigated. The relationship between the receptor expression and serum immune complex (IC) concentration was analysed. The decrease in mean fluorescence intensity of both Fc gamma RII and Fc gamma RIII of patients' granulocytes stained by specific monoclonal antibodies (using MoAb IV.3 and 3G8) was significant. The detected decrease of Fc gamma RII was inversely correlated with the high circulating IC level in patients' sera.
 ...
PMID:Correlation of IgG Fc receptors on granulocytes with serum immune complex level in systemic lupus erythematosus. 748 65

In systemic lupus erythematosus accompanied by the abnormal appearance of circulating immune complexes (ICs), Fc gamma receptor (FcR)-mediated IC handling in macrophages including Kupffer cells has been shown previously. However, sinusoidal endothelial cells (SECs) largely ingest soluble immunoglobulin (Ig) G-ICs through FcRs. In this study, the character, antigenic expression, and activity (i.e., ligand-binding capacity of SEC FcRs in NZB/NZW F1 lupus and NZW nonautoimmune mice) were immunohistochemically analyzed using monoclonal antibody (MAb) 2.4G2 to FcRs and peroxidase-antiperoxidase IgG as a ligand on cryosections. MAb 2.4G2 stained SECs and blocked the ligand binding of SEC FcRs in both mice strains. The staining intensities with MAb 2.4G2 in SECs and the FcR activities in SECs alone and all sinusoidal cells in both mice strains reached their maximum values at the age of 5 months. Staining intensities in NZB/W F1 were significantly higher at 1 and 2 months and lower at 9 months than those in NZW. The number of Kupffer cells detected by MAb F4/80 to macrophages in both mice strains gradually increased until 5 months, but their number in NZB/W F1 at 9 months was twice as large as that in NZW. In conclusion, SEC FcRs in mice are low-affinity FcRs that react with MAb 2.4G2. The data of FcR activity suggest no impairment of the FcR-mediated IgG-IC binding on SECs in NZB/W F1 in early life.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Fc receptors in liver sinusoidal endothelial cells in NZB/W F1 lupus mice: a histological analysis using soluble immunoglobulin G-immune complexes and a monoclonal antibody (2.4G2). 754 88

B cells are stimulated by antigens or by polyclonal activators such as bacterial lipopolysaccharide (LPS) to produce antibody. In nonautoimmune strains of mice, LPS-stimulated antibody responses are inhibited by crosslinking the B cell antigen-receptor (BCR), while antigen-driven responses are shut down by co-crosslinking the BCR and the receptor for the Fc portion of IgG (Fc gamma R). BCR signals are poor at shutting off LPS-induced antibody production, including anti-ssDNA antibody production, in B cells from NZB, NZB/WF1, and BXSB lupus-prone mice but not MRL/lpr or NZW mice. In the current studies, the defect in NZB B cells was shown to be independent of T cells and macrophages. The inheritance pattern of resistance to BCR ligation of LPS-induced Ig production in BXSB mice could not be assigned to either founding strain. In New Zealand mixed (NZM) recombinant inbred mice, slightly but significantly more resistance was found in a line (NZM2410) that demonstrates a greater degree of clinical autoimmunity than another line (NZM64) with fewer autoimmune problems. The autoimmune defect is specific to BCR signals because inhibition of LPS activation by ligation of MHC class II occurs normally in NZB B cells. Bypassing the BCR by direct stimulation of second messengers with phorbol esters or ionomycin did not overcome the defect, suggesting that defects in downstream signaling events, rather than in the BCR mechanism itself, are responsible for the reduced ability to inhibit the LPS response in NZB B cells. The inability of the BCR signaling pathway to control LPS-induced Ig production in NZB mice was apparent at the level of H mu-chain mRNA for secreted IgM. These results suggest that autoimmunity-associated B cell defects in BCR signaling and subsequent regulation of LPS-driven antibody responses have a number of inheritance patterns and involve downstream events in signaling pathways in B cells. The defect can result in aberrant regulation of H mu-chain mRNA levels for secreted IgM production, and may be a predisposing factor in murine systemic autoimmune disease.
 ...
PMID:Defective antigen-receptor-mediated regulation of immunoglobulin production in B cells from autoimmune strains of mice. 763 46

Murine monoclonal antibodies (mAbs) to human beta 2-glycoprotein I (beta 2GPI), a plasma protein required for the binding of some antiphospholipid antibodies, have been shown to possess lupus anticoagulant properties and to activate platelets via Fc gamma receptor (Fc gamma R) crosslinking. Here we investigated their ability to induce polymorphonuclear leukocyte (PMN) functional responses. The six mAbs (IgG1 isotype) tested in combination with beta 2GPI led to a concentration-dependent activation of human PMNs as appreciated by granule release, H2O2 production, and cytosolic Ca2+ increase. This activation process was accompanied by the enhancement of PMN-mediated heparan sulfate loss from the endothelial cell line EA.hy 926 without evidence for cell lysis or detachment. F(ab')2 fragments of one of the mAbs bound to PMNs in a beta 2GPI-dependent manner but were devoid of activating effects. Carbamylated beta 2GPI was unable to mediate PMN-antibody binding and subsequent activation. In addition, cationization of beta 2GPI or removal of its sialic acid groups led to higher efficiency in binding to the PMN surface and triggering activation in comparison with the untreated protein. Thus, the process of PMN activation depends on mAb binding to these cells through both Fab (via beta 2GPI) and Fc domains, as confirmed by the suppression of all responses upon treatment with an anti-Fc gamma RII, but not anti-Fc gamma RIII, antibody. Our data suggest a model of cellular activation by beta 2GPI-dependent antiphospholipid antibodies.
 ...
PMID:Neutrophil activation by anti-beta 2 glycoprotein I monoclonal antibodies via Fc gamma receptor II. 788 9

There is a powerful evidence suggesting that etiology and pathogenesis of systemic lupus erythematosus has both genetic and environmental components. Unfortunately, understanding the genetics of lupus has been impeded by knowing the pattern of inheritance. Indeed, a complex mode of inheritance for the lupus disease phenotype is suggested by the known characteristics of this disorder. Twenty-five multiplex pedigrees for lupus have been enrolled and have been used to evaluate power to reveal linkage. The power to find linkage in these pedigrees is greater for autosomal recessive than for autosomal dominant modes of inheritance. Once 100 similar pedigrees are available for analysis our results predict that linkage is likely to be present for genetic models with relatively relaxed requirements. At loci operating by autosomal recessive inheritance linkage should be detectable despite genetic homogeneity as low as 40% and penetrance as low as 50%. For loci operating by autosomal dominant inheritance genetic homogeneity must be 60% or more when penetrance is as low as 50% to be able to establish linkage. Available preliminary data are also consistent with a possible genetic linkage of Fc gamma RIIIPMN with lupus in American Black pedigrees multiplex for lupus.
 ...
PMID:Systemic lupus erythematosus: considerations for a genetic approach. 796 78

The expression of Fc gamma RI, Fc gamma RII, and Fc gamma RIII (the IgG receptors CD64, CD32, CD16) as well as CR3 (the C3bi receptor, CD11b) on monocytes in the blood of patients with systemic lupus erythematosus (SLE) was investigated. The relationship between the receptor expression and the serum immune complex (IC) concentration was analysed. The decrease in mean fluorescence intensity (FI) of the Fc gamma RII of patients' monocytes stained by specific monoclonal antibodies (MoAb IV3) was very close to statistical significance (P = 0.052). The expression (FI) of CR3 (using MoAb OKM1) on monocytes of patients was also decreased, but not significantly. The detected decrease of Fc gamma RII and CR3 was inversely correlated with the high circulating immune complex level in patients' sera. At the same time, Fc gamma RI expression on SLE monocytes (using MoAb 32) was significantly elevated and this change was in parallel with the serum IC concentration.
 ...
PMID:Correlations of monocyte phagocytic receptor expressions with serum immune complex level in systemic lupus erythematosus. 797 54

A group of Venezuelan patients with SLE showed an increased proportion of responders to Leu-4, an anti-CD3 MoAb of the IgG1 class, compared with ethnically matched non-SLE patients and healthy controls. The rate of proliferative responses or IL-2 production induced by MoAb Leu-4, and the helper effect of macrophages from Leu-4 responders on T cells from a third-party donor were comparable in patients and controls. No significant differences in the binding of murine IgG1 molecules by macrophages from SLE patients and controls were observed. The proportion of monocytes/macrophages expressing Fc gamma RI was significantly higher in SLE patients. However, the expression of FcRII, the type capable of supporting Leu-4-mediated responses, and of Fc gamma RIII was comparable in monocytes from SLE patients and controls. Our results suggest that Venezuelan patients with SLE may have a genetic predisposition for the expression of the phenotypic variant of Fc gamma RII capable of binding murine IgG1 molecules.
 ...
PMID:Increased proportion of responders to a murine anti-CD3 monoclonal antibody of the IgG1 class in patients with systemic lupus erythematosus (SLE). 825 2

To investigate the prevalence of autoantibodies directed against Fc gamma RII (CD32) and Fc gamma RIII (CD16), 151 serum samples from patients with different autoimmune diseases and 25 samples obtained from healthy individuals were assayed by ELISA on microtiter plates coated with recombinant truncated Fc gamma RII and Fc gamma RIII protein. Class specificity was defined with anti-IgG, anti-IgM, and anti-IgA reagents. High titers of circulating IgM autoantibodies reacting with both Fc gamma RII and Fc gamma RIII were characteristic for SLE and rheumatoid arthritis patients. Sera from patients with Raynaud's syndrome showed predominantly IgG reactivity with Fc gamma RIII. Sera from patients with progressive systemic sclerosis showed both IgG and IgM Fc gamma RII and Fc gamma RIII reactivity. Many patients diagnosed with degenerative osteoarthritis also had IgG autoantibodies, directed primarily against Fc gamma RII with lesser reactivity toward Fc gamma RIII. Further study is needed to correlate these findings to clinical characteristics of the different diseases.
 ...
PMID:Specificity and class distribution of Fc gamma R-specific autoantibodies in patients with autoimmune disease. 825 99

Fifty patients (41 females and 9 males, ranging in age from 12 to 79 years) with systemic lupus erythematosus (SLE) and 20 normal controls were evaluated for the presence of plasma cell-free Fc gamma receptor III (Fc gamma RIII) using an ELISA based upon a sandwich of two monoclonal antibodies. The standard curve was obtained with serial dilutions of recombinant Fc gamma RIII. In the patients, the cell-free Fc gamma RIII levels ranged from to 1.76 micrograms/ml, while it did not exceed 0.21 microgram/ml in the controls. Assuming that the cutoff is 0.25 microgram/ml, 11 SLE patients and no controls had elevated cell-free Fc gamma RIII levels in the serum. Among the SLE patients, the level of cell-free Fc gamma RIII was significantly lower (p = 0.05) in 4 patients with sicca syndrome than in the remaining 46. Furthermore, cell-free Fc gamma RIII levels appeared to be lower in 11 patients with renal involvement than in those without. For the biological parameters, we observed that the 27 patients who presented lymphopenia also had a lower level of cell-free Fc gamma RIII when compared to the 23 patients without lymphopenia (0.09 +/- 0.19 versus 0.35 +/- 0.52 microgram/ml; p = 0.05). Circulating cell-free Fc gamma RIII may originate from shedding by presumably activated polymorphonuclear cells.
 ...
PMID:Cell-free Fc-gamma receptor III in sera from patients with systemic lupus erythematosus: correlation with clinical and biological features. 826 Aug 47

The triggering of the respiratory burst by phagocytosis via different receptors in monocytes of patients with systemic lupus erythematosus (SLE) was investigated. The superoxide anion synthesis was assayed by reduction of ferricytochrome C that was inhibited by superoxide dismutase. The mononuclear cell suspensions were triggered by IgG-coated latex, C3 complement fragment-coated and uncoated yeast (Saccharomyces cerevisiae). Superoxide generation induced by phagocytosis via Fc gamma R was decreased in monocytes of patients with SLE. On the other hand, MoAbs against Fc gamma RI, Fc gamma RII and especially CR3 could also induce superoxide anion synthesis. At the same time, superoxide generation induced by anti-CR3 could be inhibited with C3-coated yeast.
 ...
PMID:Triggering of respiratory burst by phagocytosis in monocytes of patients with systemic lupus erythematosus. 840 96


<< Previous 1 2 3 4 5 6 7 8 Next >>