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)

Sera from 36 subjects with systemic lupus erythematosus (SLE) were examined for extractable nuclear antigen (ENA) autoantibodies by immunoassay with the ribonucleoprotein (RNP) subset being determined by immunodiffusion. The prevalence of the genetic markers of HLA, the fourth complement component (C4) and properdin factor (Bf), which are all coded for within the major histocompatibility complex on chromosome 6 were analysed in relation to various parameters of these autoantibodies. The following associations were observed: The lowest ENA antibody titres of the RNP negative group were associated with HLA A9 (P less than 0.05), while the lowest RNA-ase sensitive ENA (RSE) subset antibody levels were associated with HLA Dr 1 (P less than 0.05). For the complement markers, C4 AQo was associated with the lowest affinity ENA antibodies (P less than 0.05), while the BF F allele and Fs phenotype had lower RSE antibody levels than did the S allele (P less than 0.05) and the SS phenotype (P less than 0.05) respectively. This study demonstrated diverse association between various MHC markers and ENA antibody parameters, indicating that there are distinctive immunogenetic influences over ENA autoantibodies in SLE.
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PMID:Extractable nuclear antigen (ENA) autoantibodies in SLE: an immunogenetic relationship with HLA, C4 and Bf alleles. 348 67

We demonstrated previously that B151K12 T cell hybridoma produces two distinct B cell differentiation factors, B151-TRF1 and B151-TRF2, capable of inducing differentiation of antigen-activated and unstimulated B cells into antibody-forming cells, respectively. In the present study we investigated the pathophysiologic relation of these factors with factors obtained from MRL/MP-lpr/lpr(MRL/lpr) mice and (C57BL/6 X DBA/2)F1 (BDF1) mice undergoing chronic graft-vs-host reaction (GVHR), representing a murine model of systemic lupus erythematosus with polyclonal B cell activation associated with the T cell hyperfunction. The functional and biochemical analyses revealed that B151-TRF2-like, but not B151-TRF1-like, activity was found in culture fluid supernatant (CFS) of lymphoid cells from MRL/lpr mice with lymphoproliferative syndrome. On the other hand, both B151-TRF1- and B151-TRF2-like activities were detected in CFS prepared from spleen cells of BDF1 mice undergoing chronic GVHR by the inoculation of parental DBA/2 spleen cells. Interestingly, spleen cells of BDF1 mice transferred with DBA/2 thymocytes preferentially elaborated B151-TRF1-like factor. Because BDF1 mice transferred with DBA/2 spleen cells but not with DBA/2 thymocytes developed a SLE-like syndrome exemplified by the appearance of Coombs' antibody and proteinuria, it seemed likely that production of B151-TRF2-like factor was closely associated with the onset of autoimmune disease. In fact, B151-CFS containing B151-TRF2 but not B151-TRF1 activity could induce a striking autoantibody production both in vivo and in vitro as detected by PFC responses of normal mice to bromelain-treated mouse red blood cells (BrMRBC). Moreover, it was demonstrated that in vitro anti-BrMRBC PFC responses induced by semipurified B151-TRF2 was markedly inhibited by addition of relevant anti-Ia antibody to the culture. Thus, the present study demonstrates that B151-TRF2 represents one of the B cell differentiation factors responsible for polyclonal B cell activation leading to autoantibody production.
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PMID:Polyclonal B cell activation by a B cell differentiation factor, B151-TRF2. III. B151-TRF2 as a B cell differentiation factor closely associated with autoimmune disease. 354 18

Isolated inherited deficiency states of almost every complement protein have been recognized. Almost all are autosomal recessive traits. Deficiency of the early-acting components C1, C4 and C2 is associated with increased risk of immune complex disease, particularly systemic lupus erythematosus. Patients with deficiency of C3, factor I or factor H have increased susceptibility to infection by pyogenic bacteria, whereas those with deficiencies of properdin, C5, C6, C7 or C8 are prone to systemic neisserial infection. Inherited deficiency of C1 inhibitor is transmitted as an autosomal dominant trait, is genetically heterogeneous, and is associated with attacks of angioedema and consumption of C4 and C2. There is evidence that a plasmin-modified fragment of C2 is responsible for the angioedema in this disorder. Administration of androgens tends to correct the biochemical abnormalities of hereditary angioedema and to prevent attacks.
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PMID:Inherited deficiencies of complement components in man. 357 Mar 60

MRL/Mp-+/+ (+/+) and MRL/Mp-lpr/lpr (lpr) mice spontaneously produce the SLE-specific anti-nuclear antibody, anti-Sm. Previous work on the clonality and specificity of the anti-Sm response has suggested that the Sm antigen itself induces this autoantibody. In the present work, we have directly investigated the immunogenicity of Sm. In short-term cultures, Sm antigen was shown to be important for the de novo generation of anti-Sm PFC in vitro. The addition of purified Sm to cultures of spleen cells from anti-Sm-positive lpr mice augmented the number of anti-Sm PFC on day 4. Also, the addition of Fab anti-Sm to such cultures inhibited the generation of anti-Sm PFC, probably by blocking determinants on endogenous Sm. The ability of the autoantigen to initiate anti-Sm generation in vivo was investigated by hyperimmunizing +/+ mice with Sm from rabbit or mouse sources. Such mice specifically produced antibodies that recognized both rabbit and mouse Sm as determined by ELISA. The IgG subclass distribution of these induced antibodies was similar to that of spontaneous anti-Sm antibodies found in older mice of the same strain. Our data indicate that the Sm antigen can both initiate and augment production of the anti-Sm autoantibody. These findings provide additional evidence that the spontaneous anti-Sm response in SLE is antigen driven.
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PMID:Role of the Sm antigen in the generation of anti-Sm autoantibodies in the SLE-prone MRL mouse. 370 Oct 58

Anti-DNA antibody responses by cultured circulating lymphocytes from SLE patients and by the tonsillar lymphoid cells of normal donors were detected and enumerated by a sensitive specific ELISA of culture supernatants, or by a hemolytic anti-DNA PFC assay. Although spontaneous IgM and IgG anti-DNA and anti-ssDNA responses were characteristic of SLE lymphocytes and spontaneous IgM anti-ssDNA responses were characteristic of tonsillar lymphocytes, the circulating lymphocytes of normal controls never produced anti-DNA antibodies spontaneously, and rarely after PWM stimulation. The anti-DNA antibody PFC response of tonsil lymphocytes correlated directly with the total number of immunoglobulin-producing cells measured by a reverse hemolytic PFC assay. Mixing experiments in which we employed cultures of comparable numbers of separately enriched autologous circulating and tonsillar B and T cells revealed that tonsillar tissue contained an enriched population of anti-DNA antibody precursor B cells and/or helper T cells.
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PMID:The in vitro production of anti-DNA antibody by cultured peripheral blood or tonsillar lymphoid cells from normal donors and SLE patients. 390 65

A patient with herpes gestationis, 6 of 6 patients with bullous pemphigoid, and 5 of 25 patients with systemic lupus erythematosus were found to have properdin deposited along the skin basement membrane.The patient with herpes gestationis demonstrated by immunofluorescence basement membrane deposition of C3 and C5 in the absence of C1q, immunoglobulins, and light chains. A second patient with herpes gestationis had C3 deposition with no demonstrable immunoglobulins or light chains. A thermolabile humoral factor(s) capable of depositing C3 (without C1q or C4) on normal skin basement membrane was found in the sera of both patients with herpes gestationis. No anti-basement membrane antibodies could be demonstrated in the sera of these patients.The patients with systemic lupus erythematosus and bullous pemphigoid who manifested properdin deposition also showed skin basement membrane deposits of C1q, C4, C3, C5, and immunoglobulins. C3 proactivator (C3PA) was also found deposited along the skin basement membrane of three patients with systemic lupus erythematosus and all six bullous pemphigoid patients. This study provides suggestive evidence that activation of complement is occurring via the alternate pathway in herpes gestationis. In systemic lupus erythematosus and bullous pemphigoid, both the classical (antibody) mediated activation of complement as well as the alternate pathway may be operative.
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PMID:Evidence for complement activation via the alternate pathway in skin diseases, I. Herpes gestationis, systemic lupus erythematosus, and bullous pemphigoid. 435 64

Serological and immunopathological studies of human glomerulonephritis have suggested that alternate pathways of activation of the third component of complement may be important in some forms of glomerulonephritis. We have investigated the role of two alternate pathway proteins, properdin and C3 proactivator, in 22 patients with chronic membranoproliferative glomerulonephritis, 21 patients with systemic lupus erythematosus, 20 patients with acute poststreptococcal glomerulonephritis, and 19 patients with other forms of renal disease. C3 (measured at beta(1)A), properdin, and C3 proactivator were assayed by single radial immunodiffusion. In sera with low beta(1)A (< 2 SD), mean properdin was most significantly decreased in patients with acute poststreptococcal glomerulonephritis but was also significantly decreased in chronic membranoproliferative glomerulonephritis and in untreated systemic lupus erythematosus. Properdin levels in other renal disease, acute glomerulonephritis, and chronic membranoproliferative glomerulonephritis with normal beta(1)A levels were not significantly different from normal. A positive correlation between beta(1)A and properdin levels in individual sera was present in all diseases except systemic lupus erythematosus. Serum C3 proactivator was markedly decreased in active systemic lupus erythematosus and there was a positive correlation between beta(1)A and C3 proactivator levels in systemic lupus erythematosus and other renal diseases but not acute poststreptococcal glomerulonephritis. Properdin in fresh sera from four patients with systemic lupus erythematosus and five with chronic membranoproliferative glomerulonephritis showed increased migration toward the cathode on immunoelectrophoresis, suggesting in vivo change of the properdin molecule. The observation of reduced serum levels of properdin and C3 proactivator and altered electrophoretic migration of properdin in some patients with glomerulonephritis provide new evidence for participation of these alternate pathway proteins in glomerulonephritis.
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PMID:Properdin anc C3 proactivator: alternate pathway components in human glomerulonephritis. 463 Sep 81

The investigation concerned 33 systemic lupus erythematosus (SLE) patients assigned to three groups representing mild SLE, more severe extra renal SLE, and SLE with significant renal involvement. In patients with extrarenal disease, the inflammatory plasma protein response was often pronounced during exacerbation, as evidenced by markedly increased concentrations of C-reactive protein (CRP), alpha 1-antichymotrypsin, alpha 1-antitrypsin, and orosomucoid. CRP responses were rare in patients with renal involvement, despite the increased concentrations of other acute-phase reactants in some of these patients. Superimposed bacterial infections were not clearly distinguished by raised CRP concentrations. The classical pathway of complement was activated in all patients during exacerbation, as indicated by increased concentrations of C1r-C1s-C1 inactivator complexes and C2a fragments. C1, C2, and probably also C3 activation varied according to the amounts of circulating C1q-binding immune complexes, as measured by solid-phase assay. Manifest hypocomplementemia was usually associated with glomerulonephritis. Participation of complement components in the inflammatory plasma protein response apparently counteracted the development of hypocomplementemia in many patients with extrarenal SLE. Circulating C3d was detected in all patients during exacerbation of renal disease and in most patients with severe extrarenal manifestations. Inverse relationships were found between immunochemical C2 concentrations and the percentage of cleaved C2 and between C3 and C3d. There was no appreciable consumption of factors B and D and properdin of the alternative pathway in the patients. High concentrations of factor D, a low molecular weight protein, were exclusively found in patients with renal involvement and could be ascribed to retention due to reduced glomerular filtration.
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PMID:Complement components, complement activation, and acute phase response in systemic lupus erythematosus. 608 33

Isolated genetic deficiencies of individual components of the complementary system have been described in man for all the components of the classical pathway and the membrane attack complex as well as for Factor I, Factor H and properdin. It is only for Factor B and Factor D of the alternative pathway that homozygous deficiency states are not so far known. Complement deficiency states provide the most direct way of looking at the role of the complement system in vivo and emphasize the importance of complement in resistance to bacterial infection and in particular to infection with Neisseria. This association is not unexpected since in vitro studies have shown complement to be an efficient enhancer of phagocytosis and inflammation. The particularly frequent occurrence of neisserial infection may be ascribed to the ability of these organisms to survive in phagocytic cells so that the plasma cytolytic activity provided by complement is needed to kill them. On the other hand the strong association between complement deficiencies and immune-complex diseases--especially systemic lupus erythematosus--was unexpected and seems paradoxical in view of the large part played by complement in the pathogenesis of immune complex mediated tissue damage. The paradox can be explained in part by the necessity for an intact complement system in the solubilization and the proper handling of immune complexes. It is also likely that complement deficiency can allow the persistence of low virulence organisms that produce disease solely by an immune complex mechanism. Recently described deficiencies of complement receptors and their effects in vivo are described.
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PMID:Inherited complement deficiencies. 614 84

Laboratory parameters were studied in 8 systemic lupus erythematosus patients during periods of high and low disease activity, mainly as defined by clinical criteria. Renal manifestations were present in 6 patients 5 of which showed antibodies to native DNA. C-reactive protein was raised in 3 patients. Only 1 of these showed a superimposed bacterial infection. Markedly high concentrations of C1r-C1s-C1 inactivator cOmplexes (C1r-C1s-Cl IA) in the sera provided direct evidence of C1 activation independent of disease activity. During active disease. C1r-C1s-C1 IA were correlated with C1q binding immune complexes as measured by solid phase, but not by fluid phase assay. Immunochemical concentrations of C1q, C4 and C3 and functional C2 were decreased in active SLE, consistent with sequential activation of the classical pathway. Discrepancies were noted between functional and immunochemical assay for C2 but not for factor B. Although essentially within the normal range, the levels of C1s, C4 binding protein, C5 and properdin were lower during active than during inactive disease. The concentrations of the factors B, I and H did not suggest involvement of the alternative pathway. 1 exceptional patient showed low factor B, a relative decrease of factor I and the presence of Bb fragments in plasma during active SLE. Markedly high factor D values were found. This could partly be explained by reduced renal function.
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PMID:Complement components, C1 activation and disease activity in SLE. 629 80


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