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)

Human-human hybridomas obtained from the separate fusion of tonsillar lymphoid cells from three different normal individuals to the lymphoblastoid cell line GM 4672 were screened by ELISA for the presence of autoantibody to Ro(SS-A). Those anti-Ro(SS-A) reactive hybridomas were then cloned by limiting dilution. Nineteen monoclonal IgM anti-Ro(SS-A) antibodies were obtained, which showed specificity to Ro(SS-A) by ELISA and Western blotting (60 kDa). Some of these monoclonal anti-Ro(SS-A) antibodies showed reactivity to DNA (2/19), cardiolipin (9/19), Sm/RNP (15/19) by ELISA, and to IgG (12/19) and La(SS-B) (19/19) by ELISA and Western blotting. None showed reactivity to the unrelated proteins casein and BSA, nor to RNA. Inhibition studies revealed that the binding to Ro(SS-A) of both IgM hybridoma monoclonal and SLE serum polyclonal IgM anti-Ro(SS-A) antibodies was inhibited with Ro(SS-A), La(SS-B) and Sm/RNP but not with IgG, DNA, RNA and BSA. These data indicate that (1) normal humans have the genetic potential to express antibodies to Ro(SS-A) and (2) the normally derived monoclonal and SLE serum IgM anti-Ro(SS-A) antibodies share similar antigen binding properties and therefore may possibly originate from a common pool of precursor B cells.
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PMID:Characterization of human-human hybridoma monoclonal anti-Ro(SS-A) autoantibodies derived from normal tonsil lymphoid cells. 148 88

Primary oral antigen exposure normally induces mucosal immunity and an active suppression of the systemic immune response. Patients with systemic lupus erythematosus (SLE) have increased antibodies to bovine gamma-globulin (BGG), which suggested a possible failure of oral tolerance in SLE. We examined this possibility in murine lupus. NZB/W females were fed BGG or saline and were subsequently immunized ip. Primary and secondary responses were assessed. At 1 month of age the mice tolerized normally in response to feeding with BGG but, at 4 months of age, not only did they not tolerize, the mice fed BGG had a 5- to 7-fold higher response to parenteral immunization than did the saline-fed mice. Control strain mice tolerized normally at both ages (a 5- to 10-fold lower response). Conversely, when fed ovalbumin, NZB/W females tolerized normally at both 1 and 4 months of age, and patients with SLE had normal levels of antibody to this antigen. However, we also found increased levels of antibodies to bovine casein in SLE patients, and found that NZB/W mice failed to orally tolerize with this antigen at either 1 or 4 months of age. Thus, the failure of oral tolerance in the NZB/W mice appears to be antigen specific and age dependent and, at least with respect to these three antigens, appears to parallel the antibody patterns seen in human SLE.
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PMID:Failure of oral tolerance in (NZB X NZW)F1 mice is antigen specific and appears to parallel antibody patterns in human systemic lupus erythematosus (SLE). 295 Oct 41

Self recently described a substrate system for alkaline phosphatase (AP)-dependent ELISAs which markedly increased sensitivity, compared to using p-nitrophenyl phosphate. This increase is achieved by having AP, the primary enzyme, produce an activator for a secondary enzyme-substrate system, within which marked amplification occurs. We adapted this technique to study antibodies to casein, bovine serum albumin, ovalbumin, and cardiolipin in the sera of patients with systemic lupus erythematosus (SLE) and normal individuals. The new substrate system yielded titres 30-50-fold higher than those with p-nitrophenyl phosphate (Sigma 104, p-NPP). In addition, when used in a solid-phase C1q binding assay we were able to use a 1 : 100,000 dilution of AP-conjugated anti-human IgG with the amplified substrate, compared to the 1 : 1000 dilution needed with p-NPP. This system is extremely valuable because of its flexibility. It can either be very sparing of limited samples, or if the added sensitivity is not needed, 100-fold less AP conjugate may be used. Thus rare or expensive conjugates can be significantly conserved.
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PMID:A substrate amplification system for enzyme-linked immunoassays. Demonstration of its general applicability to ELISA systems for detecting antibodies and immune complexes. 349 82

The role of nutrition in modulating autoantibody expression in murine lupus has become well documented. One such nutritional factor, zinc deficiency, has received significant attention because of the well-known effects of zinc on the immune function of genetically normal animals. Moreover zinc-deficient diets retard autoantibody production in NZB, NZB/W, and MRL/1 mice; such deprivation also enhances survival in all three strains. Because zinc nutriture influences vitamin A metabolism, it has been postulated that the immunologic effects of zinc deficiency are mediated in part by the reduction of vitamin A levels seen in zinc deprivation. To explore this possibility we studied the influence of vitamin A deficiency, in zinc well-nourished mice, on autoantibody production in NZB mice. Groups of NZB mice, beginning at 6 mo of age, were fed a vitamin A-deficient diet or a control diet ad libitum or pair-fed to the deficient group. The diet contained casein as the protein source and contained adequate levels of trace elements and vitamins. Despite our hypothesis that the reduction of autoantibodies in zinc-deficient NZB mice might be mediated by secondary vitamin A deficiency, we found that vitamin A-deficient animals manifested more severe hypergammaglobulinemia and an earlier onset of both NTA and IgM anti-erythrocyte autoantibodies than did vitamin A-sufficient mice. These results illustrate the importance of rigorous studies of select nutritional parameters and warn of the possibility of clinical harm in feeding inappropriate diets to patients with systemic lupus erythematosis.
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PMID:Nutritional factors and autoimmunity. IV. Dietary vitamin A deprivation induces a selective increase in IgM autoantibodies and hypergammaglobulinemia in New Zealand Black mice. 660 78

Thirteen patients with stage I mycosis fungoides (MF) were studied for the presence of circulating autoantibodies including cold-reactive lymphocytotoxic antibodies (LCA), antinuclear antibodies and rheumatoid factor antibodies to common food antigens, bovine gamma globulin and casein; and immune complexes as measured by cryoglobulins and I125 Clq binding. A significantly increased incidence (11/13) of LCA was found in the MF patients, and this may be related to the alterations in subpopulations of T cells seen in these patients. No significant increase in any other test was noted. there was no evidence of a diffuse hyperactivity of the humoral immune system as seen in systemic lupus erythematosus, which has a similar imbalance of T cell subpopulations.
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PMID:Humoral immunity in stage I mycosis fungoides: an increased incidence of lymphocytotoxic antibodies. 698 21

The migration inhibition factor (MIF) has been detected in sera of both amyloid patients and mice with casein-induced amyloidosis. This factor inhibits the migration of intact mouse splenocytes and peritoneal macrophages of the guinea pig. The same activity is also displayed by sera of guinea pig. The same activity is also displayed by sera of patients with chronic active hepatitis, liver cirrhosis and systemic lupus erythematosus. Spontaneous migration of splenocytes was studied in the course of casein-induced amyloidosis in mice. In the early stages of antigenic stimulation there was an increase in the cell migration activity, corresponding with the morphological picture of pyroninophilic and plasma cell proliferation. In the course of further antigenic stimulation the migration activity gradually decreases as the lymphoid tissue gets replaced by amyloid mass. MIF production during amyloidosis is discussed.
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PMID:[Macrophage migration inhibition test in mice with experimental amyloidosis]. 699 81

The acute-phase plasma protein response to disease activity in murine models of autoimmune lupus-like disease was investigated by measurement of the concentration of serum amyloid P component (SAP) in NZB X W and MRL/l mice. The levels of SAP, which is a major acute-phase protein in mice, did not rise at all in response to progression of disease in NZB X W mice between the ages of 1 and 9 mo. This resembles the behavior of acute-phase proteins such as C-reactive protein and serum amyloid A protein in human systemic lupus erythematosus, and just as in human lupus, where the occurrence of intercurrent microbial infection can stimulate an acute-phase response, so injection of bacterial lipopolysaccharide or casein into the NZB X W mice stimulated "normal" acute-phase SAP production. In marked contrast, MRL/l mice developed greatly increased levels of SAP, which correlated closely with progression of their pathology as they aged. The disease profile of the MRL/l strain includes rheumatoid factors and spontaneous polyarthritis and their SAP response resembles the behavior of acute phase proteins in human rheumatoid arthritis. Different patterns of acute-phase response in different autoimmune disorders may thus be a reflection of the genetic predisposition to particular diseases and/or contribute to their pathogenesis. The existence of animal counterparts for the various clinical patterns of human acute-phase protein production will assist in experimental investigation of the underlying mechanisms and of the biological role of the acute-phase response.
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PMID:The acute-phase response in (NZB X NZW)F1 and MRL/l MICE. 715 12

The clearance of nucleosome core particles and H1-stripped chromatin from the circulation of mice was examined. Radiolabeled chromatin preparations were injected into mice, and blood samples were obtained over 60 min. The animals were then killed, and the selected organs were collected and radioactivity was measured. The acute phase response (APR) was induced by i.p. injections of casein before some clearance studies. Serum amyloid P component, the major acute phase protein in mice, increased from 27 microg/ml to 339 microg/ml during the acute phase. The rate of chromatin clearance decreased during the acute phase in C57BL/10J mice. At 5 min, 18% +/- 3% of the originally measured radioactivity remained in control animals compared with 49% +/- 2% in acute phase animals (p < 0.001). Co-injection of either serum amyloid P component or C-reactive protein, the major acute phase protein in humans, caused a decrease in the rate of chromatin clearance similar to that observed following the induction of the APR. APR induction also caused a higher percentage of the chromatin to localize in the liver compared with the spleen, with the ratio changing from 10.2 +/- 0.7 to 16.1 +/- 1.9 (p < 0.004). In addition, the APR caused a decrease in the percentage of chromatin localized in the kidney. The lack of radioactivity associated with cells in the circulation indicates that complement is not a major factor in the clearance mechanism of chromatin. These findings suggest that the APR produces major changes in the rate and path of chromatin clearance. These changes may protect against deposition of chromatin in target organs of systemic lupus erythematosus.
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PMID:The effect of acute phase proteins on clearance of chromatin from the circulation of normal mice. 864 25

A casein kinase released from activated human platelets phosphorylates a number of plasma proteins extracellularly, and that activation of platelets in systemic lupus erythematosus patients parallels an increase in the phosphate content of plasma proteins, including C3. The present study was undertaken to characterize this platelet protein kinase and to further elucidate the effect(s) on C3 function of phosphorylation by platelet casein kinase. The phosphate content of human plasma C3 was increased from 0.15 to 0.60 mol phosphate/mol of C3 after platelet activation in whole blood or platelet-rich plasma. The platelet casein kinase was distinct from other casein kinases in terms of its dependence on cations, inhibition by specific protein kinase inhibitors, and immunological reactivity. C3 that had been phosphorylated with platelet casein kinase was tested for its susceptibility to cleavage by trypsin or the classical and alternative pathway convertases and its binding to EAC and IgG. Phosphorylation did not affect the cleavage of C3 into C3a and C3b, but the binding of fragments from phosphorylated C3 to EAC14oxy2 cells and to IgG in purified systems and in serum was increased by 1.6-4.5 times over that of unphosphorylated C3. A covariation was seen between the enhanced binding of C3 fragments to IgG after phosphorylation and an increased ratio of glycerol/glycine binding, from 2.0 for unphosphorylated C3 to 4.9 for phosphorylated C3. The present study suggests that an overall effect of phosphorylation of C3 by platelet casein kinase is to enhance the opsonization of immune complexes.
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PMID:Alterations in C3 activation and binding caused by phosphorylation by a casein kinase released from activated human platelets. 1035 96

The C-terminal peptide SmD1(83-119) has been identified as an important autoantigen in systemic lupus erythematosus (SLE). ELISA studies have shown that roughly 70% of all sera from patients with SLE react with this peptide. Previous findings revealed that the addition of blocking agents and sample dilution buffers influences the discrimination between positive and negative anti-SmD1(83-119) sera in SLE. The aim of the present study was to identify possible cofactors in the anti-SmD1(83-119) reactivity. We therefore tested SLE sera (n=6) for anti-SmD1(83-119) reactivity by ELISA and analysed the effects of different blocking agents (1% skim milk, 1% gelatin, and 1% BSA). In our investigation, lipids were extracted from skim milk using dichlomethane, and the putative fraction was tested to assess the assay's ability to discriminate between positive and negative sera. The effects of enzymatic digestion by casein were analyzed, and different concentrations of casein were used to determine the role of this protein in the detection of anti-SmD1(83-119) antibodies by ELISA. Furthermore, rabbits were immunized with SmD1(83-119) adsorbed to casein and control proteins. One percent skim milk was the most effective blocking agent and sample dilution buffer for the discrimination between positive and negative sera. As demonstrated by SDS electrophoresis, the discriminative capacity was influenced by enzymatic digestion of skim milk proteins, but not by lipid extraction. Differences in anti-SmD1(83-119) reactivity upon variation of the casein concentration suggest that the protein plays a significant role in the detection of anti-SmD1(83-119) antibodies. However, our immunisation studies did not show any effect of casein on anti-SmD1(83-119) reactivity, suggesting that it has no immunogenic effect on the anti-SmD1(83-119) response. In conclusion, casein seems to be an important cofactor in autoantibody reactivity directed against the C-terminal SmD1(83-119) peptide and probably functions by changing the conformation of the peptide's critical epitope.
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PMID:Casein is an essential cofactor in autoantibody reactivity directed against the C-terminal SmD1 peptide AA 83-119 in systemic lupus erythematosus. 1260 29


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