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)

Selective congenital deficiency in the second component of complement has been described in association with lupus erythematosus (LE) and other connective tissue disorders. We identified a 59-year-old woman with a 13-year history of cutaneous LE and no detectable serum C2. The patient's photosensitivity, large polycyclic erosive cutaneous lesions, lack of renal disease, paucity of serological findings, and high incidence of bacterial infection is consistent with previously described patients with this association. Uniquely, the patient demonstrated secondary infection with Staphylococcus aureus and Trichophyton rubrum in the skin lesions themselves. Immunologic studies disclosed depression in both humoral and cellular immunity. Moderation in her clinical disease and immunologic measurements has been observed after treatment with levamisole hydrochloride. Immunogenetic studies of the patient's four-generation kindred was consistent with an autosomal recessive inheritance of C2 deficiency genetically linked to HLA, segregating with the B18 allele. Mixed lymphocyte culture determinations reinforce evidence for linkage between the HLA-D locus and the trait for C2 deficiency.
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PMID:Hereditary C2 deficiency associated with cutaneous lupus erythematosus: clinical, laboratory, and genetic studies. 76 Jun 59

All pregnancy-associated tissues are capable of producing prostaglandins including PGI2 and TXA2. In normal pregnancy there is a dominance of PGI2 over TXA2 which may contribute to the maternal circulatory adaptation to pregnancy. Furthermore, both fetoplacental PGI2 and TXA2 production are important regulators of the fetal blood supply. It has been clearly established that in pre-eclampsia PGI2 production decreases in the fetoplacental tissues and quite probably also in the maternal tissues. The effect of this change may be further exaggerated by the simultaneous stimulation in pre-eclampsia of TXA2 production. The reason for PGI2 deficiency is not known. Other vasoactive agents, such as endothelin, may act in concert with prostaglandins. Relative PGI2 deficiency is likely to exist also in IUGR and lupus anticoagulant syndrome of pregnancy. In the latter, lupus anticoagulant may directly inhibit the synthesis of PGI2. One study suggests PGI2 deficiency also in early pregnancies of women with a history of repeated abortions. Prostaglandin production increases during full-term labour, and similar but smaller changes also occur in preterm labour. A silent bacterial infection may trigger the onset of preterm labour through cytokine-stimulated increase of prostaglandin production. No data were found on prostaglandin production in post-term pregnancies. That oligo-polyhydramnios is possibly prostaglandin mediated is suggested by the control of polyhydramnios by indomethacin treatment. Smoking decreases the production of PGI2 and possibly increases that of TXA2, which may lead to decreased blood flow and IUGR. Which constituent of cigarette smoke exerts this effect is not known. Ethanol consumption causes aberrations in prostaglandin metabolism which cannot be directly connected with fetal alcohol effects.
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PMID:The role of prostaglandins in obstetrical disorders. 147 99

Survival in systemic lupus erythamatosus (SLE) continues to improve because of better ancillary care, earlier diagnosis, and earlier treatment. However, infection remains a leading cause of morbidity and mortality in this disease. Although corticosteroids and immunosuppresives increase the risk of opportunistic infection, the SLE patient is still most at risk from common bacterial pathogens. As the prototypic immune-complex disease, patients with active SLE have low circulating complement as well as a reticuloendothelial system (RES) saturated with immune complexes. It seems intuitive that SLE patients should be most at risk for organisms dependent for their removal on the RES or complement for opsonization or bacteriolysis. The current series presents four patients with SLE and disseminated neisseria infection and brings to 14 the number of patients in the literature with disseminated neisserial infection. They are typically young, female, with renal disease, and either congenital or acquired hypocomplementemia, and may present with all features of a lupus flare. Surprisingly, they are not all on corticosteroids or immunosuppressives and have some features that are unusual for non-SLE patients with these infections. There seems to be an over-representation of Nisseria meningitidis (despite potential reporting bias), and there ironically may be better tolerance with fewer fulminant complications in patients who have complement deficiencies. The best approach for the physician treating SLE is to immunize all SLE patients with available bacterial vaccines to N meningitidis and Streptococcus pneumonia, have a low threshold of suspicion for the diagnosis of disseminated neisserial or other encapsulated bacterial infection in the SLE patient who is sick, and to treat empirically with third generation cephalosporins after appropriate cultures.
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PMID:Increased risk of neisserial infections in systemic lupus erythematosus. 228 42

Antibodies binding to solid-phase cardiolipin (anticardiolipin antibodies, ACA), which are closely associated with lupus anticoagulant activity, have been found in patients with thrombosis. ACA are often seen also in patients after acute infections. To study further our recent observation on the association between infection and cerebral infarction in young and middle-aged patients we measured anticardiolipin response (IgG, IgM, IgA) in paired sera from 54 consecutive patients with cerebral infarction under 50 years of age and in 54 community controls matched for sex and age. An elevated IgG-class ACA level or a significant change in level as observed in 2 serial samples occurred in 15 (28%) patients, but in only 4 (7%) controls (P less than 0.02). These ACA levels were only slightly elevated, and there were no patients with levels approaching values commonly seen in lupus anticoagulant-positive patients. Neither were there any patients with systemic lupus erythematosus (SLE) as an underlying disease. The combination of IgG-class ACA positivity and preceding probable bacterial infection (based on clinical, cultural or serologic data) was found in 10 patients (18%) but in only 2 controls (4%) (P less than 0.05). There were no significant differences in IgM- or IgA-class ACA between the patients and their controls. These results suggest that IgG-class ACA response associated with preceding probable bacterial infection is more common in patients with cerebral infarction than in their community controls. However, slightly elevated ACA are probably only indirect indicators of preceding infection and not directly involved in the pathogenesis of thrombosis itself.
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PMID:Anticardiolipin response and its association with infections in young and middle-aged patients with cerebral infarction. 321 44

Several different classes of autoreactive antibodies are known to exist: those that are stimulated by bacterial infection (e.g., streptococci/rheumatic fever), those that react with tissue-specific antigens (e.g., thyrotropin receptor/Graves' disease), and those that bind to ubiquitous autoantigens (e.g., DNA/systematic lupus). The origin of the last kind of autoantibody is unknown, but it now seems that their production is an inherent property of the normal immune system. Indeed, it would appear that autoantibodies of the lupus variety actually have a physiological role in normal immunity. The development of the autoimmune disease may occur when there is an "escape" from the normal function of lupus autoantibodies.
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PMID:Anti-DNA antibodies and the problem of autoimmunity. 348 64

Three cases of systemic lupus erythematosus (SLE) with pleural effusion are reviewed. The characteristics of the effusions are presented, and the literature pertaining to lupus-related effusions is reviewed. There is great heterogeneity in lupus pleural effusions. The presence of polymorphonuclear neutrophils as the predominant white cell, while consistent with SLE, should raise the possibility of complicating bacterial infection. The presence of lupus erythematosus (LE) cells in the fluid seems to be the most specific diagnostic criterion.
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PMID:Pleural effusion in systemic lupus erythematosus. 616 Jul 9

Bone marrow necrosis (BMN), defined morphologically by destruction of hematopoietic tissue, including the stroma, with preservation of the bone, is a rare syndrome. The conditions in which it is seen include sickle cell disease, acute leukemia, metastatic neoplasia, and bacterial infection, particularly when hypovolemia and septic shock are present. BMN is also associated with disseminated intravascular coagulation (DIC) following irradiation and antineoplastic therapy. The antiphospolipid syndrome (APS) is characterized by antibodies directed against the antiphospolipid substrate. Because this substrate is prominently involved in the coagulation cascade and widely distributed on cell walls, patients present with venous or arterial thromboses, recurrent abortion, thrombocytopenia, and Coombs' positive hemolytic anemia, typically with raised anticardiolipin antibodies or a diagnostic lupus anticoagulant test. BMN does not appear to have been previously recognized in this context. We report what we believe to be the first such case and suggest that the high titers of antibodies present may have played a central role in its pathogenesis.
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PMID:Extensive bone marrow necrosis associated with antiphospholipid antibodies. 777 73

Infection with gram-negative and gram-positive bacteria remains a leading cause of death in patients with systemic lupus erythematosis (SLE), even in the absence of immunosuppressive therapy. To elucidate the mechanisms that underly the increased risk of infection observed in patients with systemic autoimmunity, we have investigated host defense against bacterial infection in a murine model of autoimmunity, the MRL/Mp-lpr/lpr (MRL/lpr) mouse. Our previous study implicated transforming growth factor beta (TGF-beta) in a novel acquired defect in neutrophil function in MRL/lpr but not congenic MRL/Mp-+/+ (MRL/n) mice (Gresham, H.D., C.J. Ray, and F.K. O'Sullivan. 1991. J. Immunol. 146:3911). We hypothesized from these observations that MRL/lpr mice would have defects in host defense against bacterial infection and that they would have constitutively higher local and systemic levels of active TGF-beta which would be responsible, at least in part, for the defect in host defense. We show in this paper that spontaneous elaboration of active TGF-beta adversely affects host defense against both gram-negative and gram-positive bacterial infection in MRL/lpr mice. Our data indicate that MRL/lpr mice, as compared with congenic MRL/n mice, exhibit decreased survival in response to bacterial infection, that polymorphonuclear leukocytes (PMN) from MRl/lpr mice fail to migrate to the site of infection during the initial stages of infection, that MRL/lpr mice have a significantly increased bacterial burden at the site of infection and at other tissue sites, and that this increased bacterial growth occurs at a time (> 20 h after infection) when PMN influx is greatly enhanced in MRL/lpr mice. Most intriguingly, the alteration in PMN extravasation during the initial stages of infection and failure to restrict bacterial growth in vivo could be duplicated in MRL/n mice with a parenteral injection of active TGF-beta 1 at the time of bacterial challenge. Moreover, these alterations in host defense, including survival in response to lethal infection, could be ameliorated in MRL/lpr mice by the parenteral administration of a monoclonal antibody that neutralizes the activity of TGF-beta. These data indicate that elaboration of TGF-beta as a result of autoimmune phenomenon suppresses host defense against bacterial infection and that such a mechanism could be responsible for the increased risk of bacterial infection observed in patients with autoimmune diseases.
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PMID:Spontaneous elaboration of transforming growth factor beta suppresses host defense against bacterial infection in autoimmune MRL/lpr mice. 796 55

We have studied the ability of the lupus prone MRL lpr/lpr (MRL/lpr) and (NZBxNZW)F1 (NZB/W) female mice to raise granulocyte mediated inflammatory responses. These autoimmune strains, known to exhibit severe anergy as concerns T cell dependent immune function, are not well analysed with respect to neutrophil-mediated inflammatory responses. An in vivo model of granulocyte mediated inflammation has been developed in our laboratory. A single intradermal injection of olive oil into mouse footpad induces massive infiltration of polymorphonuclear cells (PMNC) within 24 h. This extravasation of PMNC gives rise to a localized footpad swelling, which can be easily and reproducibly measured and relates to severity of the inflammatory process. T cell independence of this inflammatory model was ascertained by in vivo T cell depletion using monoclonal antibodies to CD4 and CD8 molecules. Olive oil triggered inflammation was inducible in both young and aged lupus mice. The intensity of footpad swelling upon olive oil injection was similar in lupus mice and in healthy control strains. In contrast, aged MRL/lpr and NZB/W mice showed severely depressed T cell dependent inflammatory responses as assessed by delayed type hypersensitivity reaction to sheep red blood cells. We conclude that the PMNC mediated inflammatory potential is not affected in severely diseased lupus mice. The increased numbers of circulating PMNC together with intact PMNC function may explain why severely immune deficient lupus mice seldom show clinical signs of bacterial infection.
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PMID:Neutrophil mediated inflammatory response in murine lupus. 832 62

Systemic lupus erythematosus (SLE) is a multifactorial disease of unknown etiology. Characteristic features of SLE include (1) polyclonal B cell activation, (2) overexpression of the immune stimulatory cytokine interleukin-6 (IL-6), (3) defective tolerance to self antigens, and (4) production of anti-DNA antibodies (Ab). Bacterial infection has been suspected as a triggering factor for lupus. Bacterial DNA differs from vertebrate DNA in the frequency and methylation of CpG dinucleotides. These CpG motifs in bacterial DNA induce a variety of immune effects, including (1) polyclonal activation of murine and human B cells, (2) IL-6 secretion, and (3) resistance to apoptosis, thereby potentially allowing the survival of autoreactive cells. These results suggest that microbial DNA could therefore be a pathogenic factor in SLE. SLE patients have elevated levels of circulating plasma DNA which is reportedly enriched in hypomethylated CpGs. Genomic DNA is also hypomethylated in SLE. The purpose of this review is to summarize the immune effects of CpG motifs and to present the evidence for their possible involvement in the pathogenesis of SLE.
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PMID:CpG DNA: a pathogenic factor in systemic lupus erythematosus? 857 14


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