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)

Pepsin exists in macrophages. Phagocytosis of foreign materials increases pepsin activity in macrophages and also causes extracellular release of pepsin from macrophages. Pepsin enhances antibody production by spleen cells against heterologous materials and suppresses that against homologous materials. Pepsin selectively decomposes immune complexes at neutral pH, and intravenous pepsin ameliorates symptoms in autoimmune disease models, such as immune complex glomerulonephritis in MRL/l mice and SLE-like syndromes of NZB/W F1 mice. These results prompted us to propose a "pepsin-immunoregulation hypothesis", according to which pepsin acts as a regulating factor in the immune system.
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PMID:Pepsin-immunoregulation hypothesis. 642 15

The cytotoxic activities of lupus sera were measured against IgG Fc-receptor-bearing T lymphocytes (T gamma cells) and T lymphocytes lacking this receptor [T gamma (-) cells], and the activities were compared with the inhibitory activities of the sera for the formation of rosettes (T gamma rosettes) between T lymphocytes and ox erythrocytes sensitized with IgG antibody. The cytotoxic activities of the sera against both T gamma and T gamma (-) cells well correlated with their T gamma rosette inhibitory rates. Also, the cytotoxic activities after the removal of IgM antibodies strongly correlated with the inhibitory rates. Among them, the highest correlation was observed between IgG T gamma-specific cytotoxic antibodies and T gamma rosette inhibitory rates of the sera. Gel filtration, ultracentrifugation, pepsin digestion, and reduction and alkylation of the sera revealed that main inhibitory activities were contained in IgG fractions. These results suggested that IgG T gamma-specific antibody suppressed T gamma rosette formation and might contribute to the reduction of T gamma cell number in patients with systemic lupus erythematosus.
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PMID:Inhibition of T gamma rosette formation by the sera from patients with systemic lupus erythematosus. Relation to T gamma-specific antilymphocyte antibody. 660 75

The presence of circulating immune complexes (CIC) has been documented in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and ankylosing spondylitis (AS) by various investigators. It has been suggested that these may be used as probes to identify antigens playing a role in these pathological processes. Using a solid-phase cross-reaction assay to establish if these complexes reacted with each other in specific disease groups, it was found that polyethylene glycol (PEG) precipitates of six AS patients cross reacted in 29 of 36 tests, but reacted with SLE and RA PEG precipitates in only two of 24 tests in each case. SLE PEG precipitates cross-reacted in four of 14 tests and reacted with none of the six AS and four RA precipitates. Similarly, RA PEG precipitates did not cross-react (none of 16 tests), nor did they react with AS (none of 24 or SLE precipitates (none of 16). Similar results were observed when IgG, obtained after acid dissociation on sucrose density gradients of CIC isolated by PEG precipitation and staphylococcal protein A chromatography, was used as the solid phase component. F (ab')2 fragments with similar antibody specificity were obtained by pepsin digestion of isolated CIC from three of six AS patients. These bound radiolabelled AS PEG precipitates (2.02-2.40%) significantly more than SLE (0.22-0.28%) or RA (0.29-0.35%) precipitates. These studies demonstrate the feasibility of obtaining F (ab')2 fragments with antibody activity from isolated CIC and the presence of a disease specific antibody specificity in AS CIC. The nature of the antigen involved remains to be elucidated. Such a cross-reactive antibody specificity was not found in RA nor SLE CIC.
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PMID:Evidence for a disease specific antigen in circulating immune complexes in ankylosing spondylitis. 661 54

High dose immunoglobulin infusions showed a marked effect on platelet counts in eight out of nine chronic ITP patients and in one SLE patient. In the comparison of different IgG-preparations, the pepsin treated IgG F (ab')2 showed no platelet elevation while the sulfonated did. The elevated platelet count could not be maintained after discontinuation of IgG infusions, but in six out of ten patients the platelet level remained above the pretreatment values. This new treatment seems to be safe and effective in adulthood ITP.
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PMID:Clinical effect of intravenous immunoglobulin on chronic idiopathic thrombocytopenic purpura. 668 78

Suspensions of human platelets were incubated with various immunoglobulin preparations and subsequently stained with FITC-conjugated antisera. Incubation with monomeric, IgG, but not with monomeric IgM, IgA, IgD nor with IgE, gave a positive staining of the platelets. Incubation of platelets with monomeric IgG1 and IgG3 as well as with Fc and pFc'-fragments from IgG3 also gave a positive staining while incubation with monomeric IgG2 and IgG4 did not. Thus, IgG binds to Fc receptors on the surface of human platelets with the CH3 domain of the Fc region. Heat aggregation also caused binding of IgG2 but not with IgG4 proteins to human platelet Fc receptors. The majority of platelet preparations both from ITP and SLE patients gave a positive staining using direct immunofluorescence technique. Incubation of normal human platelets with sera from ITP and SLE patients gave a strong surface staining of normal platelets. Strong staining was also obtained with pepsin-digested sera from most patients with ITP while pepsin-digested sera from patients with SLE did not give a positive staining. It is therefore concluded that the majority of sera from patients with ITP contain antibodies with specificities for platelet surface antigens while sera from patients with SLE contain immune complexes that react with platelet Fc receptors through the Fc parts of the IgG antibodies.
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PMID:Studies on the binding of immunoglobulins and immune complexes to the surface of human platelets: IgG molecules react with platelet Fc receptors with the CH3 domain. 679 9

A solid-phase assay for the detection of anti-F(ab')2 antibodies is described. Wells of microtiter plates are coated with F(ab')2, dilutions of sera are added, and IgG bound to the solid phase is detected using peroxidase-labeled Protein A. Anti-F(ab')2 antibodies were found in 61% of sera from patients with rheumatoid arthritis, 77% with subacute bacterial endocarditis , and 34% with systemic lupus erythematosus. Simultaneous analysis of these sera for immune complexes (IC), using modified Clq and monoclonal rheumatoid factor assays, showed that a correlation existed between anti-F(ab')2 antibodies and the levels of IC. Characterization of anti-F(ab')2 antibodies by inhibition and absorption experiments and by immunological and physical means indicated that they were similar to serum proteins described in the 1960s and designated pepsin agglutinators.
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PMID:Association of anti-F (ab')2 antibodies (pepsin agglutinators) with immune complexes as determined by enzyme-linked immunosorbent assays. 697 96

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple immune disturbances whose mechanisms remain unclear. We examined the interaction of antilymphocyte antibodies with cultured normal T lymphocytes. T cells were prepared by E-rosetting after petri-dish removal of adherent cells and cultured for 2-7 d in the presence of SLE sera or normal human sera. Cultured T cells were washed and sonicated, and the amount of cell-associated IgG was quantitated by radioimmunoassay or enzyme-linked immunoassay (ELISA) methods. T cells cultured with 27 of 39 SLE sera showed marked increments of associated immunoglobulin G (IgG) although this was not observed with sera from mixed connective tissue disease patients containing high titers of ribonucleoprotein antibody or normal donors. The effective factors for IgG association in SLE sera were absorbed with normal peripheral blood lymphocytes or T cells. Anti-T cell IgG cytotoxic activity strongly correlated with T cell IgG association (P less than 0.01). T cell-associated IgG was not removed by stripping of cell membrane IgG from living cells by acid buffer treatment; indirect immunofluorescence of cells fixed after 2-4 d of culture revealed cytoplasmic IgG staining. IgG anti-T cell antibodies appeared to associate inside the cell membrane or to penetrate into the cytoplasm of cells. T cell Fc receptor blocking by heat-aggregated IgG or anti-beta 2-microglobulin antibody did not alter IgG cell association. Since pepsin-digested SLE sera showed no T cell association activity, whole IgG antibody molecules appeared to be necessary for interaction with cultured T cells. In addition, reduction and alkylation of active SLE sera completely nullified T cell reactivity. When normal T cells were cultured with SLE sera showing marked IgG T cell association, viability of cultured T cells decreased rapidly after 4 d, which suggests that IgG anti-T cell antibodies were associated with cell destruction. IgG cell-associating antilymphocyte antibodies present in SLE sera may cause T cell disturbances in vivo and may be related to the lymphocytopenia present in SLE patients.
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PMID:T lymphocyte interaction with immunoglobulin G antibody in systemic lupus erythematosus. 697 91

Epidermolysis bullosa acquisita (EBA) is an acquired blistering skin disease characterized by the presence of IgG autoantibodies that recognize type VII (anchoring fibril) collagen. In this study, we have mapped the antigenic epitopes within the type VII collagen alpha chain by Western immunoblotting analysis with sera from 19 patients with EBA, using bacterial collagenase- or pepsin-resistant portions of type VII collagen and a panel of 12 recombinant fusion proteins corresponding to approximately 80% of the primary sequence of the alpha 1 (VII) collagen polypeptide. These studies identified four major immunodominant epitopes localized within the amino-terminal, noncollagenous (NC-1) domain. In addition to EBA, sera from three patients with bullous systemic lupus erythematosus (BSLE) were tested. The pattern of epitopes recognized by these sera were similar to those noted with EBA, suggesting that the same epitopes could serve as autoantigens in both blistering conditions. In contrast, sera from healthy controls or from patients with unrelated blistering skin diseases did not react with type VII collagen epitopes. Collectively, the results indicate that the immunodominant epitopes in EBA and BSLE lie within the noncollagenous regions of type VII collagen. The precise role of the circulating autoantibodies in the pathogenesis of these blistering diseases remains to be elucidated. Conceivably, however, such antibodies could disrupt the assembly of type VII collagen into anchoring fibrils and/or interfere with their interactions with other extracellular matrix molecules within the cutaneous basement membrane zone.
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PMID:Epitope mapping of type VII collagen. Identification of discrete peptide sequences recognized by sera from patients with acquired epidermolysis bullosa. 769 88

Previous studies have shown that the majority of C1q-binding IgG in patients with systemic lupus erythematosus (SLE) is composed of autoantibodies to the collagen-like region of C1q. Mice of the MRL/l strain are considered as a murine model of human SLE and possess autoantibodies to nuclear antigens as well as IgM and IgG rheumatoid factors (RF). This study was undertaken to characterize the C1q-binding IgG in MRL/l mice. In contrast to human SLE, C1q-binding IgG in MRL/l mice showed immunochemical characteristics of immune complexes rather than those of autoantibodies to C1q. Namely, C1q-binding IgG in MRL/l mice was large-sized upon HPLC gel filtration and abolished by digestion with pepsin or by high salt concentration, and bound to the globular region of C1q. The C1q-binding activity in MRL/l mice was absorbed by double-stranded DNA- or single-stranded DNA-cellulose. The medium-sized immune complexes containing RF have been well documented in MRL/l mice. In this study, however, mouse IgG-Sepharose failed to absorb fully C1q-binding IgG. We conclude that the majority of C1q-binding IgG in MRL/l mice consists of large-sized immune complexes containing antibodies to DNA.
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PMID:C1q-binding immunoglobulin G in MRL/l mice consists of immune complexes containing antibodies to DNA. 770 71

A subset of SLE patients has serologically detectable autoantibodies to the ribosomal P proteins (anti-P). We reported the discovery of covert anti-P antibodies and their masking IgG-inhibitory antibodies in the sera of healthy adults. The aim of this study was to determine if these IgG-inhibitory antibodies are anti-idiotypic antibodies (anti-Ids). IgG and IgG-depleted fractions of plasma from two healthy adults were assayed for inhibition of anti-P F(ab')2 binding to the ribosomal P proteins in immunoblot. Anti-P antibody activity was completely inhibited by plasma IgG, whereas there was no inhibition by IgG-depleted plasma. IgG-inhibitory antibodies recognized a cross-reactive epitope among anti-P from different SLE patients. Plasma IgG from one healthy adult was depleted of pepsin agglutinators and generic anti-F(ab')2 antibodies by adsorption with an affinity column prepared with normal IgG F(ab')2. Unretained IgG bound exclusively to anti-P F(ab')2 in ELISA. Using four affinity columns, we isolated IgG anti-Ids to anti-P antibodies from four healthy adults. These purified anti-Ids bound to anti-P F(ab')2 from a healthy adult and SLE patients. They did not bind to F(ab')2 fragments prepared from normal IgG or anti-dsDNA. Ribosomal antigens blocked this anti-Id-Id interaction. Purified anti-Ids inhibited the binding of anti-P F(ab')2 from patients to ribosomal P proteins. SLE patients without overt anti-P antibodies also possessed IgG anti-Ids to anti-P antibodies. We conclude that IgG-inhibitory antibodies are anti-Ids to anti-P antibodies, and are directed to public idiotopes on anti-P antibodies. These anti-Ids may be part of an Id network that regulates anti-P antibody expression, and perhaps pathogenicity.
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PMID:Anti-idiotypic antibodies prevent the serologic detection of antiribosomal P autoantibodies in healthy adults. 964 75


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