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 major cellular antigens recognized by autoantibodies in SLE and other systemic autoimmune diseases have been identified and characterized over the past 25 years. The pioneering studies of Eng Tan demonstrate the importance of autoantibodies as diagnostic markers. However, why certain autoantibodies, such as anti-Sm, are pathognomonic of SLE, while others are markers of other autoimmune disease subsets, remains unanswered. This central question continues to drive much current research into the pathogenesis of SLE. Features of the autoantigens recognized by autoantibodies may provide important clues to the causes of lupus. Most autoantigens in systemic autoimmunity are multicomponent nucleoprotein complexes. These particles are encountered by the immune system as units, resulting in the tandem production of autoantibodies recognizing several components of the same complex. However, the intermolecular-intrastructural spreading of autoimmunity is regulated by mechanisms that at present are defined poorly. Also unexplained is the observation that the antigenic determinants recognized by autoantibodies are restricted and frequently correspond to active sites or functional domains. Analysis of experimental models of autoimmunity suggests that altering the structure of autoantigens, due to abnormal protein-protein interactions, hapten binding, altered degradation, or other mechanisms, could help to explain both the restricted patterns of autoantibody spreading and the selective targeting of antigenic sites. This may be a worthwhile area for further investigation of the pathogenesis of systemic autoimmune diseases.
Mol Biol Rep 1996
PMID:Features of autoantigens. 911 32

MRL/Mp-lpr/lpr mice develop a spontaneous lupus syndrome, including hypergammaglobulinemia, autoantibodies, glomerulonephritis, and lymphadenopathy. To investigate the role of lymphocytes subsets in the pathogenesis of disease, lupus-prone MRL mice deficient in alpha beta T cells, gamma delta T cells, or both were generated. Mice deficient in alpha beta T cells developed a partially penetrant lupus syndrome, characterized by lymphadenopathy, elevated levels of class-switched immunoglobulins, an increased incidence of antinuclear antibodies, and immune deposits in kidneys which progressed to renal insufficiency over time. In comparison to wild type animals, gamma delta T cell-deficient animals developed an accelerated and exacerbated disease phenotype, characterized by accelerated hypergammaglobulinemia and enhanced autoantibody production and mortality. Repertoire analysis of these latter animals identified polyclonal expansion (V beta) of alpha beta CD4+ B220-cells. Mice lacking both alpha beta and gamma delta T cells failed to generate class-switched autoantibodies and immune complex renal disease. First, these findings demonstrate that murine lupus in the setting of Fas-deficiency does not absolutely require the presence of alpha beta T cells, and they also suggest that a significant basis for MRL/lpr disease, including renal disease, involves alpha beta T cell-independent, gamma delta T cell dependent, polyreactive B cell autoimmunity, upon which alpha beta T cell-dependent mechanisms aggravate specific autoimmune responses. Second, these data indicate that gamma delta T cells partake in the regulation of systemic autoimmunity, presumably via their effects on alpha beta CD4+ B220-T cells that provide B cell help. Finally, these results demonstrate that MRL/lpr B cells, despite their intrinsic abnormalities, cannot per se cause tissue injury without T cell help.
Mol Biol Rep 1996
PMID:T cells in murine lupus: propagation and regulation of disease. 911 36

Analysis of somatic mutations revealed that induction of anti-dsDNA autoantibodies from SLE patients are antigen driven and thus T cell dependent. Since DNA per se has repeatedly been shown not to be immunogenic, various mechanisms leading to the production of anti-dsDNA-antibodies have been discussed including the role of oligonucleosomes. In the present study we demonstrate that the percentage of macrophage engulfing apoptotic cell material was significantly reduced in SLE as compared to control patients. These data suggest that, in contrast to a non-inflammatory clearance of apoptotic cell, phagocytosis of apoptotic cell material may be decreased in SLE patients, possibly leading to a presentation of autoantigens and thus possibly triggering an autoantibody response to nucleoproteins.
Mol Biol Rep 1996
PMID:What triggers anti-dsDNA antibodies? 911 39

The 8.12 idiotype is expressed in elevated titer in the serum of patients with systemic lupus erythematosus and is a marker for a subpopulation of anti-DNA antibodies that possess a V(lambda)II encoded light chain. This study utilized a eukaryotic expression system to identify the structural basis for expression of this idiotype. Reversion of the 8.12+ DSC light chain to the hslv215.23/DPL11 germline gene reveals that the 8.12 idiotype is encoded in the germline. The 8.12+ DSC and the 8.12 AS17 light chains, both belonging to the V(lambda)II family, were subjected to site directed mutagenesis, to localize amino acids important for expression of the 8.12 idiotype. Point mutations were performed in CDR1, CDR2, FR3 and CDR3, in positions where the 8.12+ DSC differs from the 8.12-AS17. Amino acids in CDR1 and the CDR2 proximal region of FR3, but not the J proximal region of CDR3, play a crucial role in 8.12 reactivity. The 3-D structure of Mcg, a human IgG1, with which DSC shares a sequence homology of 92.3% has been examined to visualize the effect of each of the mutations and to identify the surface on DSC that comprises the idiotype.
Mol Immunol 1996 Nov
PMID:Molecular mapping of the 8.12 SLE-associated idiotype specificity at the single amino acid level. 912 62

Following administration of certain chemicals (heavy metals or lupus-inducing drugs), H-2s mice produce autoantibodies reacting with various nuclear antigens such as fibrillarin in the nucleolus and histones in chromatin. In the present study, we have immunized A.SW (H-2s) mice and their congenic counterparts A.BY (H-2b) mice with bovine thymus nuclei in Freund's adjuvant. As was previously observed with lupus-prone mice, such active immunization did not elicit antinuclear antibodies in any of the experimental groups. Surprisingly, the A.SW immunized with nuclei in adjuvant developed high titers of IgG antibodies that reacted exclusively with synthetic polycations. We obtained several monoclonal IgG antibodies from these mice and verified that these polycation-reactive antibodies were not directed against a specific nuclear antigen. The genetic analysis of the monoclonal antibodies further confirmed their clonal diversity. The mechanisms leading to the appearance of antibodies reactive with highly basic molecules in A.SW mice may be related to their predisposition to produce autoantibodies to cationic nuclear antigens (fibrillarin, histones) during chemically-induced autoimmunity.
Mol Immunol 1997 Jan
PMID:Induction of anti-polycation antibodies in H-2s mice by immunization with nuclear antigens. 918 75

Several annexins have been implicated in the pathogenesis of benign and malignant neoplasms of different origins. In some tumours a suppressive action of annexins has been shown, whereas studies of other tumours indicate an involvement of annexins in tumour progression. In the light of the expression of annexins at distinct episodes of fetal development these observations point towards a functional role of annexins in cellular development and differentiation. This view is supported by data that link certain annexins to distinct pathways of signal transduction. Auto-antibodies against several annexins have been detected in patients with autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease. Until now it is unclear whether their presence reflects a relevant pathogenetic mechanism or merely represents an unspecific expression of a raised autoimmunity in these patients.
Cell Mol Life Sci 1997 Jun
PMID:Annexins in cancer and autoimmune diseases. 923 Sep 35

We have earlier reported that patients suffering from acquired immuno-deficiency syndrome (AIDS), systemic lupus erythematosus (SLE) with vasculitis, Wegner granulomatosis and certain types of late stage cancer have interferon inhibitory activity in their serum. The purpose of this study was to identify the factor(s) involved in this interferon inhibitory activity. Twenty patients with advanced AIDS, twenty patients with SLE and vasculitis and twenty normal healthy controls between ages 25-40 years were studied. In contrast to normal, healthy controls, significant interferon inhibitory activity was found in AIDS and SLE patients. This appears to be largely due to: (a) increased soluble circulating interferon alpha/beta receptors, (b) increased prostaglandin E2 levels which inhibits interferon and (c) a interferon inhibitory protein. Further understaging of the nature of interferon inhibitory activity in the patient's sera and development of anti-interferon inhibitory agents would greatly enhance interferons potential as a treatment modality.
Res Commun Mol Pathol Pharmacol 1997 Jun
PMID:Mechanism(S) of interferon inhibitory activity in blood from patients with AIDS and patients with lupus erythematosus with vasculitis. 926 85

The nucleotide sequence of the region of the Epstein-Barr virus genome that specifies two small ribonucleic acids (RNAs), EBER 1 and EBER 2, has been determined. Both of these RNAs are encoded by the right-hand 1,000 base pairs of the EcoRI J fragment of EBV deoxyribonucleic acid. EBER 1 is 166 (167) nucleotides long and EBER 2 is 172 +/- 1 nucleotides long; the heterogeneity resides at the 3' termini. The EBER genes are separated by 161 base pairs and are transcribed from the same deoxyribonucleic acid strand. In vitro, both EBER genes can be transcribed by RNA polymerase III; sequences homologous to previously identified RNA polymerase III intragenic transcription control regions are present. Striking similarities are therefore apparent both between the EBERs and the two adenovirus-associated RNAs, VAI and VAII, and between the regions of the two viral genomes that specify these small RNAs. We have shown that VAII RNA as well as VAI RNA and the EBERs exist in ribonucleoprotein complexes which are precipitable by anti-La antibodies associated with systemic lupus erythematosus. Finally, we have demonstrated that the binding of protein(s) from uninfected cells confers antigenicity on each of the four virus-encoded small RNAs.
Mol Cell Biol 1981 Sep
PMID:Striking similarities are exhibited by two small Epstein-Barr virus-encoded ribonucleic acids and the adenovirus-associated ribonucleic acids VAI and VAII. 927 91

Apo-1/Fas (CD95) is a transmembrane protein expressed on the cell surface that is involved in apoptosis and plays an important role in the function and regulation of the immune system. Aberrant expression of the Apo-1/Fas gene product has been reported in a number of immune-related disorders, such as autoimmune lymphoproliferative syndrome and systemic lupus erythematosus in humans. Mutations in the coding sequence of the Apo-1/Fas gene have been reported in the former condition, whereas no abnormalities of the gene have been found to account for the increased gene expression noted in SLE. We screened the whole 5' flanking region of the Apo-1/Fas gene encompassing over 2000 bp for mutation(s)/polymorphism(s) using multiplex PCR, single-strand conformation polymorphism (SSCP) analysis and sequencing techniques, and identified two polymorphisms in this region. The first polymorphism is a CG-->CA substitution at -1377 nucleotide position within the silencer region, which neither creates or deletes any restriction enzyme sites but alters the transcription factor SP-1 binding site. This polymorphism is noted in 20% of normal Caucasians. The second polymorphism is an GA-->GG substitution at -670 nucleotide position in the enhancer region that creates a MvaI restriction fragment length polymorphism (RFLP) and abolishes the binding site of nuclear transcription element GAS. The MvaI RFLP is polymorphic with heterozygosity of 52% and the frequency of G and A alleles are 0.49 and 0.51, respectively. The identification and characterisation of these two new polymorphisms, particularly the MvaI RFLP marker, provides new genetic markers and may prove useful for further studies on the regulation of apoptosis mediated by the Apo-1/Fas gene on human chromosome 10q23.
Mol Immunol 1997 Jun
PMID:Identification and characterization of polymorphisms in the promoter region of the human Apo-1/Fas (CD95) gene. 939 60

Using lectin blots in conjunction with peptide mapping, alpha 2-macroglobulin micropurified from systemic lupus erythematosus (SLE) patients was shown to become abnormally glycosylated suggesting the occurrence of complex glycosylation in this pathological condition. To confirm there is indeed a quantitative increase in specific monosaccharides in this protein; alpha 2-macroglobulin was micropurified from a battery of 37 serum samples which included 6 normal donors (3 male and 3 female), 23 SLE patients, 6 rheumatoid arthritis patients, 1 mixed connective tissue disease patient, and 1 Sjogren's syndrome patient; for carbohydrate analysis. It was noted that the concentration of total monosaccharides in alpha 2-macroglobulin micropurified from serum samples of SLE patients is significantly higher than normal donors with a mean +/- SD of 188 +/- 410 micrograms/mg protein (SLE, n = 23) versus 14.5 +/- 4 micrograms/mg protein (normal, n = 6) even though there was a high variation in the level of monosaccharides among the SLE patients. An increase in oligosaccharides in alpha 2-macroglobulin from SLE patients compared to normal subjects was confirmed by concanavalin A (Con A) blots using peptide fragments derived from the micropurified protein. Since the interaction of peptide fragments derived from alpha 2-macroglobulin with Con A requires the presence of mannose and/or glucose residues, we have also examined if there are any correlations between the levels of mannose and glucose in alpha 2-macroglobulin and SLE. The concentration of mannose (38 +/- 60 micrograms/mg protein) in alpha 2-macroglobulin derived from SLE patients was significantly higher than normal donors (mannose, 4.8 +/- 1 micrograms/mg protein) however, the concentration of glucose in alpha 2-macroglobulin derived from SLE patients when compared to normal donors was not statistically significant, 18 +/- 20 micrograms/mg protein in SLE versus 2 +/- 0.5 micrograms/mg protein in normal donors due to high variation between samples. Also, the concentration of galactose in alpha 2-macroglobulin from SLE patients was significantly higher than normal donors (45.7 +/- 173 micrograms/mg protein versus 0.13 +/- 0.03 microgram/mg protein). These results illustrate quantification of carbohydrate in selected glycoproteins such as alpha 2-macroglobulin may be a novel and alternative clinical marker for SLE.
Biochem Mol Biol Int 1997 Dec
PMID:An increase in the carbohydrate moiety of alpha 2-macroglobulin is associated with systemic lupus erythematosus (SLE). 944 26


<< Previous 1 2 3 4 5 6 7 8 9 10