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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 hybridoma monoclonal antiplatelet antibodies were produced using tonsillar lymphocytes from a nonthrombocytopenic male fused to the lymphoblastoid cell line GM 4672. Twenty of 472 (4%) IgM producing hybridomas had antiplatelet reactivity as detected by ELISA. Thirteen of these antiplatelet antibody producing hybridomas with clonality ensured by limiting dilution were tested for antigenic specificity. Two different and mutually exclusive groups of antiplatelet antibodies were identified. The first group of antiplatelet antibodies (four clones) showed reactivity that was limited to DNA and anionic phospholipids. Antibodies from the second group (seven clones) showed reactivity by immunoblotting to a variety of platelet proteins including platelet glycoprotein IIb. These antibodies did not bind DNA nor anionic phospholipids. These studies indicate that lymphocytes of normal human origin have the genetic potential to produce antiplatelet autoantibodies. These antiplatelet antibodies segregate on the basis of their target antigens into two major groups, which mimic the target antigens held responsible for antiplatelet autoantibodies in disease. These include glycoproteins (typical of chronic idiopathic thrombocytopenic purpura) and DNA and/or anionic phospholipids (typical of the lupus anticoagulant syndrome).
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PMID:The production of human monoclonal antiplatelet auto-antibodies derived from human lymphocytes of normal origin: reactivity to DNA, anionic phospholipids and platelet proteins. 141 9

Anti-lamin B autoantibodies are associated with both systemic lupus erythematosus (SLE) and autoimmune liver disease. We examined the possibility that the underlying clinical feature in patients with anti-lamin B autoantibodies might be chronic autoimmune liver disease, and whether the hypergammaglobulinemia present in both disorders is involved in generating anti-lamin B autoantibodies. A lamin B fusion protein (MLB1), consisting of amino acids 77-533 of lamin B fused to TrpE, was used to screen sera from 84 patients with SLE for anti-lamin B autoantibodies. 3/4 prototype human lamin B antisera, 5/84 SLE sera (6%), and 0/30 sera from healthy individuals reacted with MLB1 on immunoblots at a 1:500 dilution. Of the 9 anti-lamin B autoantibody positive patients studied, all but 1 fulfilled at least four ARA criteria for SLE. None of the patients displayed evidence of chronic autoimmune liver disease, suggesting that autoimmune liver disease is not strongly associated with anti-lamin B antibodies in SLE. In SLE, as in "lupoid hepatitis", anti-lamin B autoantibodies are often produced transiently during periods of increased disease activity. Although polyclonal hypergammaglobulinemia is also associated with increased activity of both diseases, anti-lamin B autoantibody production in 2 patients was independent of total immunoglobulin levels, antibodies to irrelevant proteins, and production of some other autoantibodies. Thus, polyclonal activation is insufficient to explain either the initiation or regulation of anti-lamin B autoantibody production, supporting the hypothesis that antinuclear antibodies are antigen-selective.
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PMID:Onset and regulation of anti-lamin B autoantibody production is independent of the level of polyclonal activation. 193 14

Human hybridomas were produced by fusion of the GM 4672 cell line with lymphocytes from the peripheral blood, spleen, and bone marrow of patients with systemic lupus erythematosus. Lymphocytes were also obtained from normal human fetal liver of 12 weeks' gestation. The influence of anatomical source, fusion ratio, pre-stimulation with pokeweed mitogen, HLA match, and disease activity at the time of fusion was studied. Supernatants were screened for immunoglobulin secretion and binding to DNA, cardiolipin, poly(ADP-ribose), and histones by enzyme-linked immunoassay. A total of 28 fusions from 14 donors and 6 fusions with fetal lymphocytes were performed. The spleen was found to be the most efficient source of lymphocytes, with a fusion ratio of 1:1 resulting in a maximum yield of 27 clones/10(7) lymphocytes fused. HLA matching was a factor influencing the outcome with HLA A2 matching being the most important. Pre-stimulation with pokeweed mitogen did not improve the fusion frequency, and fusions using lymphocytes from patients with active disease were only marginally more successful. Over 95% of clones secreted immunoglobulin; autoreactivity was found against DNA, histones, cardiolipin, and poly(ADP-ribose). All hybrids with autoreactivity secreted IgM.
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PMID:Analysis of factors affecting human hybridoma production. 210 60

Human lymphocytes derived from peripheral blood, the spleen and lymph nodes were fused to the HAT-sensitive heteromyeloma cell line CB-F7. The Ig-producing initial cell lines were selected, and the supernatants were further analyzed for specific antigen binding (ELISA). IgM-antibodies were found which reacted with self- and non-self antigens of different molecular origin (nucleotides, proteins, carbohydrate structures). These antibodies were called multireactive (multispecific). The multispecific IgM-producing human hybridomas occurred with higher frequencies in the spleen (6.9% of IgM-producers) cell fusions than in experiments where peripheral blood-derived lymphocytes were fused (2.7%). There were no hybridomas producing multireactive antibodies detected in fusion material from lymph nodes. The greatest number of multireactive IgM was seen when PBL from SLE or anti-HIV-positive patients were hybridized to CB-F7 cells. Representative cell lines were cloned and recloned. The multireactivity of the IgM produced by really monoclonal cells, however, was preserved.
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PMID:Occurrence of hybridomas producing multispecific IgM in human x (human-mouse) fusions with lymphocytes from different human immune compartments. 262 50

The blood-brain barrier separates brain interstitial space from blood and is formed by brain capillary endothelial cells that are fused together by epithelial-like tight junctions. Study of the blood-brain barrier traditionally has been a relatively arcane field, even for neurobiologists. However, advances over the last 10 years in understanding the transport physiology and cell biology of the brain capillary endothelial cell now provide insights into the pathogenesis of such problems as brain glucopenia, hepatic encephalopathy, therapeutic efficacy of alpha-methyldopa, brain edema in diabetic ketoacidosis, Alzheimer's disease, brain tumors, and lupus cerebritis.
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PMID:Blood-brain barrier: interface between internal medicine and the brain. 287 46

A 6-thioguanine-resistant human B-lymphoblastoid cell line, HO-323, was isolated for making human-human hybridomas with high efficiency. Fusions with peripheral blood lymphocytes of systemic lupus erythematosus (SLE) patients and lymphocytes isolated from lymph nodes of lung and breast cancer patients yield constantly more than one hybridoma clones per 10(5) HO-323 cells plated. HO323 cells also fused with lymphocytes from normal peripheral blood to give hybridomas in the same efficiency. The HO-323 cells were diploid with 46 chromosomes and non-secretors of immunoglobulins. This parent cells doubled every 15 hr and could proliferate in serum-containing medium, even if they were plated at low cell density of less than 10(3) cells/ml. The cells could grow in serum-free medium as well as in serum-containing medium, and the resultant human-human hybridomas could also grow in the same media.
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PMID:HO-323, a human B-lymphoblastoid cell line useful for making human-human hybridomas. 348 76

Systemic lupus erythematosus-like graft-versus-host (GVH) disease was induced in 10-week-old male (C57BL/10 X DBA/2) F1 mice by the intravenous injection of spleen and thymus cells (2:1) from 10-week-old male DBA/2 mice. GVH mice were bled at regular intervals 1 month after injection. Antibody to nuclear antigens (ANA) were detected by immunofluorescence using HEp-2 cells as substrate, and antibody to histones and DNA were detected by enzyme-linked immunosorbent assay (ELISA). The titer and frequency of ANA were found to relate directly to the number of donor cells injected. In order to determine the spectrum of ANA in GVH disease, mice were reinjected with optimum cell numbers (120 X 10(6], and splenocytes from two mice with high titer ANA were fused to mouse myeloma cell line P3/X63Ag8.653. Hybridomas were analyzed for ANA by immunofluorescence and ELISA. Sixty-eight clones were found which secreted ANA. Of these, 59% produced antibody to double-stranded DNA, single-stranded DNA, and/or histones and the remainder gave a variety of nuclear immunofluorescence patterns including speckled, homogeneous, nuclear matrix, and nucleolar. This study indicates that GVH disease provides an excellent source of splenocytes for the production of ANA-producing hybridomas as well as a model for the study of autoimmunity.
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PMID:Monoclonal autoantibodies to nuclear antigens from murine graft-versus-host disease. 349 80

Mitochondrial autoantibodies are characteristic of the disease primary biliary cirrhosis (PBC), but the immunoreactive mitochondrial antigens have not been defined. We used a rat liver cDNA library in lambda gt 11-Amp3 to clone a 1370-base pair insert that coded for a polypeptide reactive with PBC sera. This insert was subcloned for expression into pBTA224, a plasmid vector in the same reading frame as lambda-Amp3. A positive clone, designated pRMIT, that expressed a fused polypeptide of 160 kd, was recognized by 25 of 25 sera from patients with PBC and none of 96 sera from normal persons or patients with systemic lupus erythematosus, rheumatoid arthritis, or chronic active hepatitis. This fused polypeptide was shown to correspond with the 70 kd mitochondrial autoantigen by several experiments. First, lysates of pRMIT in J101 absorbed out the 70 kd reactivity of PBC sera when probed against fractionated placental mitochondria. Second, affinity-purified antisera reactive with the fused polypeptide also reacted with the 70 kd mitochondrial antigen. Third, such affinity-purified antisera produced the characteristic anti-mitochondrial pattern of immunofluorescence on tissue sections. Finally, immunization of BALB/c mice with the fused polypeptide elicited antibodies to mitochondria. These murine antibodies reacted with the 70 kd mitochondrial protein and also produced typical mitochondrial immunofluorescence on tissue sections. The nucleotide and amino acid sequence of the recombinant protein, which encodes for approximately a 48 kd protein, showed no significant homologies with known proteins, and there were no homologies with mitochondrial genomic DNA. The availability of a recombinant form of the 70 kd mitochondrial autoantigen will allow several definitive questions to be addressed in PBC, including identification of B cell epitopes, T cell recognition, and a model of PBC in mice.
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PMID:Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recognized in primary biliary cirrhosis. 357 77

MRL/lpr/lpr (MRL/l) mice develop a lupus-like syndrome and a disease histologically and serologically similar to human rheumatoid arthritis. Their sera contain polyclonal IgM rheumatoid factors (RF) reactive with all murine IgG subclasses (frequently strongest with IgG2a) and several heterologous IgG. To examine the repertoire and epitopic specificities of these RF, we fused splenocytes from 3.5-mo-old seropositive MRL/l mice with appropriate myeloma partners and derived 1,723 hybridomas of which 23 secreted IgMRF. These monoclonal IgMRF bound to murine IgG only, not to other murine isotypes. Eight murine IgG subclass-specific clonotypes were identified. Most clones reacted with either multiple IgG subclasses or with IgG2a alone. A few clones reacted solely with IgG2b but none reacted exclusively with IgG1 or IgG3. Monoclonal IgMRF with exclusively anti-IgG2a activity exhibited allotypic specificity, reacting, with few exceptions, with a, c, and e, but not b, d, or j IgG2a allotypes. Four clonotypes could be distinguished by cross-reactivity with IgG from species other than mice. Monoclonals possessing activity against several murine subclasses cross-reacted extensively with heterologous IgG, including all human IgG subclasses without allotypic restrictions. Monoclonal IgMRF specific for murine IgG2a or 2b did not cross-react with heterologous IgG. Based on the absence of cross-reactions by IgG2a-specific monoclonal autoantibodies, certain peptides of the IgG CH2 and CH3 domains appear to generate the antigenic determinants of the anti-IgG2a RF in MRL/l mice. All of the monoclonal RF bound to Fc and, with one exception, not to Fab fragments of murine IgG. Binding of the monoclonal RF to substrate IgG was not inhibited by Clq, thus excluding the Clq-binding site at the CH2 domain as one of the responsible epitopes in the induction of MRL/l RF. mIgMRF could be categorized as strongly, weakly, or noninhibitable by protein A, which interacts with IgG molecules at or near the CH2-CH3 junction. Inhibition appears to be caused by conformational changes and/or steric shielding of certain IgG areas distant from this junction and not by identical binding sites between protein A and RF. Certain of the mIgMRF that were weakly or not at all inhibitable by protein A were found to cross-react equally well with human Fc (CH2-CH3 domains) and pFc' (CH3 domain) fragments, indicating that the binding site for these monoclonals is at the CH3 domain. Monoclonal RF were devoid of anti-double-strand DNA, anticollagen, or antipeptidoglycan pentapeptide cross-reactivity, but one of the monoclonals cross-reacted with histones, four with single-strand DNA, and one with both histones and single-strand DNA.
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PMID:Monoclonal IgM rheumatoid factors derived from arthritic MRL/Mp-lpr/lpr mice. 622 85

The utilization of one human lymphoblastoid cell line in fusion experiments with peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE) has made it possible to define efficient and reproducible conditions for the production of anti-DNA-secreting human-human hybridomas. This investigation, using the human lymphoblastoid cell line GM 4672 fused in the presence of 44% polyethylene glycol with lymphocytes from SLE patients, demonstrated a maximal yield of 22.8% hybridomas, 17% of which produced anti-DNA antibodies. We were able to define, in two independent laboratories, that the maximal yield of hybridomas occurred when the lymphocyte to GM 4672 cell ratio was 1:1 and cells were seeded in 2.0 ml wells at a concentration of 4 X 10(5) cells/well. This report demonstrates the reproducibility of human-human hybridoma production with the GM 4672 cell line and the establishment of efficient conditions for the production of anti-DNA autoantibodies from SLE patients.
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PMID:Influence of fusion cell ratio and cell plating density on production of human-human hybridomas secreting anti-DNA autoantibodies from patients with systemic lupus erythematosus. 650 May 83


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