Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neonatal lupus is a model of passively acquired autoimmunity in that immune abnormalities in the mother lead to the production of antibodies that cross the placenta and injure the developing fetus. Congenital complete heart block (CCHB), a permanent manifestation of neonatal lupus, is detectable after 18 wk gestation. Transient manifestations include cutaneous, hepatic, and hematologic abnormalities that occur at variable frequency. To date, there is a universal association of CCHB with maternal antibodies to SSA/Ro-SSB/La ribonucleoproteins, detectable by high ratio monomer:crosslinker SDS-immunoblot. Intriguingly, cardiac disease and often other manifestations are not present in the mother, raising the hypothesis that there is differential expression and/or accessibility of SSA/Ro-SSB/La antigens in fetal vs. adult tissues. CCHB may be a final consequence of a more widespread inflammatory response in the heart, including the existence of an associated myocarditis. In contrast to the in utero onset of CCHB, skin lesions generally become apparent after birth. Ultraviolet exposure may be an initiating factor and exacerbate an existing rash. Several studies have documented the predominance of DR3 alleles in mothers of affected offspring, frequently associated with the extended haplotype A1,B8. Available evidence suggests that fetal genetic differences in the major histocompatibility complex (MHC) do not influence susceptibility. The recommended clinical approach includes obstetric and rheumatologic management of both the fetus identified with CCHB and the fetus with a normal heart beat but at high risk of developing CCHB. Fetal echocardiogram is essential in diagnosing and following disease and may suggest the presence of an associated myocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neonatal lupus syndromes. 128 97

The aim of this work was to characterise the eye muscle antigens reacting with autoantibodies from Graves ophthalmopathy patients to elucidate the function of these antibodies. As estimated by ELISA test antibodies of IgG class reacting with porcine microsomal membranes are present in about 25% of patients while of IgM class in about 15% of patients with Graves ophthalmopathy. Their presence do not correlate with ophthalmopathy index, neither they have relation to treatment. Anti eye muscle antibodies were present at some stages of the disease in three patients who develop ophthalmopathy, from the group of 26 patients treated during one year for hyperthyroidism. However, sporadically these antibodies were found also in about 20% of patients with Hashimoto disease, Lupus erythematosus or Scleroderma. Some of them cross react with antigens of skeletal muscle and liver. Eye muscle antigens reacting with patients antibodies are localised in plasma membranes and in membranes of smooth reticulum. Affinity purification of solubilised porcine eye muscle membrane proteins on a column with immunoglobulins from pooled serum of patients resulted in 23 fold purification of the antigen. The sensitivity of ELISA was not significantly increased by the use of affinity purified antigen, however some of previously negative ophthalmopathy sera gave positive reaction. Porcine eye muscle membrane proteins were separated by SDS PAGE and transferred to nitrocellulose. The reactions of electroblotted proteins with sera from patients with Graves ophthalmopathy and also sera from healthy controls shown very complex pattern. There was not a single antigen or antigens reacting only with antibodies present in sera of ophthalmopathy patients and not in controls. Patients sera reacted more often than control sera with an antigen of about 40 kDa. The reaction of sera from some patients with proteins about 100, 70 and 65 kDa were stronger than between these proteins and control sera. No changes in the pattern of reaction between antibodies and eye muscle antigens were noticed in serum of the same Graves' patient with or without ophthalmopathy during one year follow up and treatment, regardless of clinical course of the disease. When human eye muscle membrane fractions from tissue obtained during strabismus repair or at autopsy was used for immunoblotting, smaller number of proteins reacted with autoantibodies. Again there was no single antigen or antigens reacting with antibodies from sera of all Graves ophthalmopathy patients. Sera of some patients reacted with antigens about 50 kDa, not recognized by controls. The results of present study show, that the anti eye muscle antibodies are present in some of Graves ophthalmopathy patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Muscle antigens recognized with autoantibodies in patients with Graves' ophthalmopathy]. 134 58

Since systemic lupus erythematosus most frequently affects women of childbearing years, the management of patients during pregnancy is an important and common problem facing the clinician. This review concerns the effects of pregnancy on the course of maternal disease and fetal well-being. On the maternal side are the problems of renal disease which may exacerbate and be difficult to differentiate from pre-eclampsia especially when occurring in the third trimester. An active urinary sediment, falling C3 and CH50 and elevated complement split products of the alternative pathway and terminal attack complex may serve as useful parameters of lupus activity. In general, maternal disease is not an imposing threat and prospective studies suggest that the exacerbation rate is not significantly greater in the pregnant lupus patient than in the non-pregnant patient. On the fetal side are the problems of placental insufficiency and in utero attack on developing organs. Maternal antibodies such as those reactive with negatively charged phospholipids are associated with second trimester miscarriages and suggested, but not firmly established, thrombosis of placental vessels. The placental transfer of maternal antibodies against components of the rapidly expanding group of SSA/Ro-SSB/La ribonucleoproteins is strongly implicated in the transient and permanent manifestations of neonatal lupus. Using various techniques for defining the specificity of the antibody response most associated with heart block, the data suggest that mothers whose sera contain antibodies which recognize antigens of SSA/Ro-SSB/La on SDS-immunoblot are at greatest risk. In the absence of antibodies to SSB/La, mothers whose sera contain antibodies reactive only to bovine SSA/Ro by ELISA do not appear to be at high risk. A rational approach to in utero treatment of autoantibody mediated fetal myocarditis includes plasmapheresis and the use of dexamethasone. Finally, the safety of the commonly used medications for the treatment of lupus such as the nonsteroidal anti-inflammatory agents, glucocorticoids and anti-malarials during gestation and breast feeding, is addressed.
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PMID:Systemic lupus erythematosus and the maternal-fetal dyad. 228 64

Anti-histone antibodies have been reported in a number of human autoimmune diseases, most notably idiopathic and drug-induced lupus erythematosus. In the current study, anti-histone antibody activity was detected using ELISA and electroblotting techniques in sera from autoimmune NZB/W, MRL-lpr, and MRL-(+)/+ mice. Anti-histone activity increased with age, maturing earlier in females, in both NZB/W and MRL-lpr mice. Testosterone treatment decreased anti-histone activity in NZB/W mice and estrogen treatment from 2 weeks of age increased anti-histone activity in MRL-lpr mice, suggesting that gonadal hormones modified the expression of autoantibodies recognizing these protein antigens. Estrogen also increased serum IgG levels in MRL-lpr mice. Sex hormones affected expression of antibodies recognizing soy milk proteins but not ovalbumin in a similar manner. Nitrocellulose Western blots of SDS gels probed with sera from both types of autoimmune mice most often demonstrated reactivity with histone1. Some mice, usually mature females, also recognized histone4, histone3, and histone2.
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PMID:Anti-histone antibodies in the serum of autoimmune MRL and NZB/NZW1 F1 mice. 230 40

We have previously described a monoclonal antibody, B16G, which has been found to be specific for T-cell derived suppressor factors (TsF). B16G has been shown to react with T-suppressor cells, TsF in the spleen of normal or tumor-bearing mice, the TsF produced by tumour-specific, or hapten-specific T-cell hybridomas, and with polyclonal whole human TsF isolated from tonsillar tissue. This pan-reactivity inherent to the B16G antibody suggests that it recognizes some common, shared epitope of the TsF molecule. In this study, we have used B16G as a probe to isolate a TsF-producing T-cell hybridoma, S-50, from CBA mice (H-2k) that is specific for the Lupus-associated antigen, RNP-Sm. The TsF bound specifically to RNP-Sm and inhibited the production of anti-RNP-Sm antibody cell cultures from MRL-lpr mice. SDS-PAGE analysis of purified S-50 TsF revealed a B16G-reactive band with a molecular weight of 43 kd.
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PMID:Isolation and characterization of a T-suppressor factor specific for the lupus-associated autoantigen RNP-Sm. 249 18

We have found evidence for a human alloantigenic system on the very late activation protein -2 (VLA-2) heterodimer (platelet GPIa/IIa). Sera from two patients with systemic lupus erythematosus (SLE) contained antibodies that immunoprecipitated surface molecules from platelets and fibroblasts that comigrated on SDS-PAGE and two-dimensional O'Farrell gels with platelet GPIa (VLA-alpha2 chain) and platelet GPIIa (VLA-beta chain). These SLE antibodies were alloreactive as they precipitated VLA molecules from only 5 of 22 normal donors' platelets and did not react with the lupus patients' own platelets, despite the expression of apparently normal amounts of VLA on the donors' cells. Two-dimensional O'Farrell analysis demonstrated no differences in the molecular weight or isoelectric point of GPIa and GPIIa obtained from platelets of alloantibody reactive or unreactive donors. Sequential immunoprecipitation experiments with VLA chain-specific monoclonal antibodies, and the pattern of immunoprecipitation of several different VLA heterodimers demonstrated that the alloantibody-reactive determinant was present on the VLA-2 heterodimer, and not other VLA molecules. Thus, these SLE sera demonstrate a previously unrecognized antigenic polymorphism of the VLA-2 (platelet GPIa/IIa) heterodimer, platelet alloantigen Hca.
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PMID:Antigenic polymorphism of human very late activation protein-2 (platelet glycoprotein Ia-IIa). Platelet alloantigen Hca. 264 23

The human erythrocyte complement receptor type 1 (CR1) is polymorphic with respect to molecular weight. Size variants with molecular weights of 190,000 (type A), 220,000 (type B) and 160,000 (type C) daltons have been detected in normal individuals (22 individuals), patients with hydralazine (Hz) lupus (n = 27), a group of Hz controls (n = 30) and the relatives of both Hz groups (27 and 11 individuals, respectively). The method of detection was SDS-polyacrylamide gel electrophoresis of erythrocyte membranes on low-percentage cross-linked gels followed by Western blotting using polyclonal rabbit anti-CR1 antibodies. In normal individuals, 77% had the A allotype and 26% carried the B allotype; amongst Hz lupus patients 67% carried the A allotype, 31% carried the B allotype, and 3% (1 individual) had the C allotype. Amongst the patients who had been on Hz but did not develop SLE, 83% carried the A allotype and 17% carried the B allotype. The AA phenotype was only found in 44% of Hz SLE patients but in 64% of normals and 70% of the Hz control group. Although not statistically significant, the results indicate a relative underrepresentation of the AA phenotype in patients with Hz-induced SLE. In addition, an equal or greater relative amount of the C allotype was detected in an Hz SLE patient with the AC phenotype. This is in contrast to lower relative amounts of the C allotype found in normal individuals with this phenotype.
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PMID:Size polymorphism of the erythrocyte complement receptor type 1 (CR1) in systemic lupus erythematosus induced by hydralazine. 272 Nov 76

Hybridization of peripheral blood lymphocytes from patients with rheumatoid arthritis has yielded 14 monoclonal antibodies which react with cultured human epithelial cells. Immunofluorescence staining identifies at last five different types of antibody. Solid phase immunosorbent assays show a variety of cross-reaction patterns with nucleic acids, proteoglycan, cardiolipin and plastic, confirming that the various antibodies react with epitopes which are at least slightly different. These conclusions are confirmed by SDS gel electrophoresis and immunoblotting on epithelial cell extracts. Similar antibodies previously found in association with lupus-like disease have been thought to be representative of the high antinuclear antibody response characteristic of lupus. Our data are more consistent with the hypothesis that all or many of these antibodies are part of the normal inflammatory response.
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PMID:Human monoclonal antibodies from patients with rheumatoid arthritis: cross reactions against cellular constituents. 390

The Sm antigen was isolated and purified from calf thymus nuclear extract by affinity chromatography. The affinity columns were made with serum antibodies from an SLE patient or an anti-Sm monoclonal antibody derived from a hybridoma cell line. Proteins eluted from these two columns had m.w. of 58,000 and 35,000 by SDS polyacrylamide gel electrophoresis. The natural conformation of this antigen appears to be 95,000 in m.w. with the 58,000 particle containing the Sm antigenic determinant. The affinity column-purified antigen detected by the human anti-Sm antibodies is also recognized by anti-Sm antibodies in murine lupus serum, as shown by solid-phase radioimmunoassay. This study 1) demonstrates the molecular and antigenic nature of the Sm antigen and 2) compares the anti-Sm binding capabilities of antibody populations present in sera from SLE patients and from MRL lpr/lpr mice.
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PMID:Molecular and antigenic nature of isolated Sm. 618

Ro and La are intracellular ribonucleoproteins that are frequent targets for autoantibodies in the sicca syndrome and in lupus erythematosus. We analyzed the m.w. of the protein (antigen) moieties of Ro and La in saline cell extracts of human spleen by SDS-PAGE and immunoblotting, gel filtration, and sucrose density ultracentrifugation with radioimmunoassay. pI values for Ro and La proteins were established by isoelectric focusing on thin layer agarose gels and immunoblotting on nitrocellulose transfers. The La protein had an m.w. of approximately 43 kd and was heterogeneous in charge, with pI values from 4.2 to 4.8. Composite two-dimensional maps developed by immunoblotting revealed a characteristic set of seven dots of m.w. 43 kd. Ro determinants were identified on polypeptides of 50 and/or 57 kd. Antigenic activity was also detected in the void volume of spleen extract fractionated by Sephadex G-200 and in 8 to 9S and greater than 19S regions of sucrose gradients, suggesting either aggregation of the Ro protein or participation in protein-protein complexes. pI values of 4.3 to 5.5 were obtained for the Ro antigen, and two-dimensional maps revealed that the 57 kd polypeptide had a similar charge heterogeneity to the La protein, whereas the 50 kd polypeptide had a different fingerprint. Immunoblotting of extracts from bovine, rabbit, and dog extracts showed that antibodies to Ro and La reacted with a limited number of polypeptides (m.w. 50 and/or 57 kd for anti-Ro and 43 or 50 kd for anti-La). These studies support the physical independence of the isolated Ro and La polypeptides, although a precursor product or functional relationship in vivo is possible. These studies also suggest that, in addition to Western blotting, techniques involving immunodeletion, isoelectric focusing with capillary immunoblotting, and 2D immunoblotting provide useful approaches to characterize saline-soluble cellular antigens.
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PMID:Partial immunochemical characterization of the Ro and La proteins using antibodies from patients with the sicca syndrome and lupus erythematosus. 671 82


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