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)

We have previously demonstrated that the introduction of the bm12 mutation into NZB mice results in animals that spontaneously produce high titer IgG autoantibodies to dsDNA. The observation that NZB.H-2bm12 develop lupus although NZB.H-2b control mice do not, provides a unique system to study the role of Th cells in the production of antibodies to dsDNA. We have isolated, in the absence of a known stimulating autoantigen, a series of seven autoreactive T cell clones that provide help in vitro for the production of IgG anti-dsDNA antibodies by syngeneic B cells. The data on these seven cloned T cell lines was compared to two cloned T cell lines specific for keyhole limpet hemocyanin. The seven cloned T cell lines, coined clones 19D, 23G, 410F, 410H, C1, C15, and C52 all show significant help in vitro for production of IgM and IgG antibodies to ssDNA and dsDNA; antibody levels increased 7- to 30-fold compared to cultures without T cells. Clones C1, C15, and C52 were furthered studied and were shown to provide help for IgM antihistone and anti-OVA responses but provided significantly less help for IgG antibodies. In contrast, keyhole limpet hemocyanin-specific cloned T cell lines TK2 and TK5 provided help for IgM antibodies to ssDNA, dsDNA, and histone, but failed to significantly increase IgG antibodies to ssDNA, dsDNA, or histone. The cloned T cell lines were restricted to H-2bm12 and proliferated only in response to APC from NZB.H-2bm12 and B6.C-H-2bm12 but not NZB.H-2b or NZB.H-2d mice; their in vitro helper activity was inhibited by antibodies to class II. All cloned T cell lines expressed Thy-1, CD5, and TCR-alpha/beta. Three of the seven clones used TCR-V beta 4. However, the V beta expression of the four remaining autoreactive T cell clones could not be determined. All of the autoreactive cloned T cell lines produce significant IL-4 but no detectable IL-2 or IFN-gamma. We believe that HPLC-purified peptides eluted from I-Abm12 molecules from APC can potentially provide insight on the putative autoantigen.
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PMID:Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice. 146 Feb 94

The regulation of Ig production by human B lymphocytes is a complex process involving interactions among B cells, APC, T lymphocytes and soluble factors including activation, growth, and differentiation factors. Components of the complement system, including C3a, C3b, C3d, and C5a, have been shown to influence various stages in this process. In this study, we demonstrate that the C1q subcomponent of complement binds to both small resting and large activated B cells and stimulates immunoglobulin production by Staphylococcus aureus Cowan-activated tonsillar B lymphocytes. This effect is present whether C1q is added to the B cells either at the beginning or near the end of a 7-day culture period and is not associated with enhancement of proliferation. The C1q stimulation of Ig production is, however, associated with increased steady state levels of mRNA for the mu Ig H chain. Furthermore, C1q stimulated IgM production by the human B cell line SKW 6.4, which is capable of secreting IgM in response to B cell differentiation factors (BCDF). SLE is a disorder frequently associated with polyclonal activation of B lymphocytes. We studied the effect of C1q on B cells from two patients with this disorder and one with an SLE-like illness, all selected for the predominance of either IgM or IgG in serum. Spontaneous or BCDF-stimulated Ig secretion was of the isotype predominant in vivo, whereas C1q selectively stimulated B cells to produce the other isotype (IgG vs IgM). Thus, C1q interacts with B lymphocytes in a manner distinct from that of BCDF found in mixed lymphocyte supernatants. C1q may be an important factor influencing the production of Ig by B lymphocytes in normal individuals and in patients with abnormalities of B cell activity.
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PMID:Complement subcomponent C1q stimulates Ig production by human B lymphocytes. 190 54

The role of IL-4 in the cellular interactions leading to the induction of CTL tolerance to H-2b alloantigens and to the development of a lupus-like autoimmune disease in BALB/c mice after neonatal injection with (C57BL/6 x BALB/c)F1 cells was investigated in vivo by using an anti-IL-4 mAb. Treatment of F1 cell-injected BALB/c mice with 15 mg of anti-IL-4 mAb was shown to interfere with tolerance induction, as assessed by the high percentages of H-2b target cell lysis and the very low or undetectable levels of B cell chimerism markers observed in these mice. Treatment with 4.5 mg of anti-IL-4 mAb interfered with tolerance induction only in one-third of F1 cell-injected BALB/c mice, but that dose induces specific modulations of the autoimmune manifestations in all mice, leading to the nearly complete prevention of the disease. In particular, the production of anti-ssDNA IgG1 and of total IgG1 and IgE antibodies was seriously affected by the treatment, as well as the proliferation and membrane Ia and K expression of F1 donor splenic cells and thymic APC. Treatment of F1 cell-injected BALB/c mice between 24 and 48 h of life with 0.5 mg of anti-IL-4 mAb did not interfere with tolerance induction, but had similar effects on the autoimmune syndrome as treatment with 4.5 mg. These results suggest that, after F1 cell injection of newborn mice, IL-4 plays an important role in the cellular interactions leading to the induction of tolerance to the corresponding alloantigens and to the development of the associated autoimmune syndrome.
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PMID:In vivo effects of anti-IL-4 monoclonal antibody on neonatal induction of tolerance and on an associated autoimmune syndrome. 221 49

Two patients with systemic lupus erythematosus (SLE) and hyperkalemia were studied. The hyperkalemia was disproportionate to the degree of renal excretory impairment. The usual causes of hyperkalemia were excluded. Basal levels of plasma renin activity (PRA) and plasma aldosterone (PAC) were low. The responses of PRA and plasma aldosterone to the combined stimulus of ambulation and furosemide were blunted. Plasma levels of 18-hydroxycorticosterone (18-OH-B) were normal. The hyperkalemia in both patients could be attributed to hyporeninemic hypoaldosteronism (HH). In one patient, the hyperkalemia was corrected by the administration of fludrocortisone. In the second patient, treatment of lupus nephritis with azathioprine, prednisone, and plasmapheresis normalized both the serum creatinine and the serum potassium.
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PMID:Hyporeninemic hypoaldosteronism in two patients with systemic lupus erythematosus. 637 83

Male BXSB mice develop lupus-like disease and die early in life (4 to 5 mo) whereas female mice do not. Others have demonstrated that CD4+ cells from male mice support B cell resistance to tolerance induction to human gamma-globulin (HGG). In this study, male and female mice tolerized at 2 mo of age with deaggregated HGG and subsequently immunized with HGG in comparison with mice immunized only were tested for anti-HGG Ab responses. CD4+ cells from draining lymph nodes of these mice were tested in culture for proliferation and production of cytokine mRNA and protein in response to HGG plus APC. Tolerized male but not female mice produced anti-HGG Abs of both the IgG1 and IgG2a isotypes. HGG-stimulated CD4+ cells from immunized male and female mice that were not tolerized produced IL-2, IL-4, IL-5, IFN-gamma, and TNF-beta mRNA as well as IL-2 and IL-4 protein, whereas tolerized, immunized mice of both sexes failed to proliferate or produce either IL-2 or IL-4 or express any cytokine mRNA in response to HGG in vitro. A resistance in tolerance induction in male mice, as determined by anti-HGG Abs, was also observed at 3 mo of age. Although a resistance to tolerance was also seen in terms of proliferation in the 3-mo-old males, production of IL-2 or IL-4 protein was still not observed. Thus, all T cell subsets identified by cytokine expression profiles were tolerized not only from females but also from males, of which the latter appeared to show some resistance to tolerance induction.
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PMID:In vivo tolerance induction and associated cytokine production by subsets of murine CD4+ T cells. 753 93

Anticardiolipin antibodies (aCL) or lupus anticoagulants (LA) have been found to exert an inhibitory action upon the activation and function of protein C, a natural coagulation inhibitor. Recently an in vitro phenomenon called resistance to activated protein C (APC resistance) has been described as the most frequent cause of hereditary thrombophilia. In order to see whether a positive association of APC resistance with aCL exists we examined plasma of 162 consecutive outpatients referred for thrombophilia screening. Further, the IgG fraction was isolated from plasma of two aCL-positive and LA-negative patients and of two aCL-negative healthy subjects by means of protein A affinity chromatography. Each of these isolates was mixed with normal plasma, and the APC resistance was assayed; 25/162 (15.4%) patients had confirmed abnormal APC resistance. Only 1/25 (4.0%) APC resistance-positive patients and 11/137 (8.0%) APC resistance-negative patients had positive IgG- and/or IgM-aCL (p = 0.5, nonsignificant). In the in vitro test system the APC resistance ratio remained unaffected after addition of normal IgG or aCL-IgG fraction in the tested normal plasma and did not deviate from the range of buffer controls. These data do not suggest any association of aCL with abnormal APC resistance. aCL-IgG fractions from aCL-positive and LA-negative plasmas do not interfere with the APC resistance test system in vitro in low concentration.
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PMID:Anticardiolipin antibodies do not seem to be associated with APC resistance in vivo or in vitro. 757 27

The influence of antibodies against phospholipids (PLa) on APC response was investigated in 155 women with a history of thromboembolism and/or repeated foetal losses. PLa were determined as antibodies against cardiolipin (CLa) and phosphatidyl serine (PSa) and as lupus anticoagulant (LA) tested by dilute Russell's Viper Venom time and by the Textarin/Ecarin ratio. APC-response was studied by a clotting (aPTT-based) and by an amidolytic (factor IXa-X-based) assay. A reduced response to APC (APC-resistance) was found in 49% of 65 PLa-positive and in 13% of 90 PLa-negative samples (chi 2 = 23.9; p < 0.5 x 10(-4)). It was more common in the samples with LA, as compared to CLa+PSa positive (58% vs. 30%, not significant). The presence of the mutation causing Arg506-Gln substitution in coagulation factor V was investigated in 84 samples. The occurrence of the mutation in APC-resistant patients with CLa+PSa or with LA in one of the two assays was similar to those without PLa (84% and 100%, respectively). In the absence of APC resistance, the occurrence of the mutation was similar in the samples with and without PLa (14% vs. 11%). Samples with LA, determined by both tests used, comprised a special group where the frequency of the mutation in the APC resistant samples was significantly reduced (p < 0.01). In the latter samples, the pathogenic mechanism of APC resistance may be connected with the influence on phospholipid membranes.
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PMID:Studies on phospholipid antibodies, APC-resistance and associated mutation in the coagulation factor V gene. 763 Dec 99

This review has stressed the common hereditary and acquired blood protein defects associated with thrombosis. The most common of the hereditary defects appear to be antithrombin, protein C, and protein S deficiency, and the most common acquired defects are anticardiolipin antibodies and the lupus anticoagulant. Therefore, these are the defects which should first be searched for in an individual with unexplained thrombosis. If these more common defects are not found, the rarer defects, including HC-II, plasminogen, or TPA deficiency, dysfibrinogenemia, elevated PAI-1, or heterozygous homocystinemia should be looked for. The incidence of activated protein C co-factor deficiency (APC resistance) is not yet clear but may also represent a common defect. PAI-1 defects may, with time, be shown to be common. Finding these defects has important implications for therapy for the individual patient and for the institution of family studies to identify, inform, and possibly treat others at risk. It is expected that as knowledge of hemostasis expands, more hereditary and acquired defects, such as elevated lipoprotein(a) or defects of extrinsic (tissue factor) pathway inhibitor (EPI, TFPI), may be associated with enhanced risks for thrombosis.
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PMID:Blood protein defects associated with thrombosis. Laboratory assessment. 778 Dec 75

Venous thromboembolic diseases are of major importance with respect to morbidity and mortality. Therefore, efficient prophylaxis is essential. Indication for thromboprophylaxis has to be made individually: In high risk situations, especially in orthopedic surgery, every patient should receive medical prophylaxis, e.g. with heparin, in addition to other preventive measures such as the wearing of elastic stockings or physiotherapy until full mobilization. For high-risk patients having a history of recurrent venous thromboembolism or which are suffering from a thrombogenic disease (e.g. myeloproliferative disorder, especially polycythemia vera, paroxysmal nocturnal hemoglobinuria, systemic lupus erythematosus, homocystinuria) or a hereditary thrombophilia (e.g. deficiency of antithrombin III, protein S, protein C or APC resistance), prophylactic measures should be more generally applied. In these patients, risk factors (e.g. oral contraceptive medication) or risk situations (e.g. long-distance travelling by car or airplane) have to be avoided whenever possible. In inevitable risk situations (e.g. perioperative or peripartal period) prophylaxis is mandatory. It is generally limited to the period of elevated thrombogenic risk and is often effected by application of a low molecular weight heparin. Patients with a history of recurrent thromboembolic events despite elimination of all avoidable risk factors should get a lifelong prophylaxis, usually with oral anticoagulants.
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PMID:[Prevention of venous thromboembolism--in whom, when and how?]. 783 22

Resistance to activated protein C (RAPC) has been described recently as a cause of trombophilia; this may justify up to 50% of thromboembolic disease without predisposing cause in patients under 45 years. A 29 years-old male with a previous deep venous thrombosis (DVT) in the lower left limb three years earlier, developed a DVT in the right lower limb after a trauma of the knee that required immobilization, was associated to pulmonary thromboembolism diagnosed by gammagraphic methods. The phlebographic study showed femoro-iliaco-caval venous thrombosis. The proband's father and a younger brother had a previous history of thrombotic episodes. The following tests, were performed in the proband and relatives: prothrombin time, aPTT, thrombin time, fibrinogen, (Von Clauss), antithrombin III (chromogenic), protein C and protein S (coagulometry and ELISA), plasminogen (chromogenic) and lupus anticoagulant (ITT, dRVVT, aCL). RAPC was evaluated in two different samples. The proband study was performed under oral anticoagulation treatment (OAT). Control groups were: 21 blood donors and 12 OAT patients. The results showed a decreased response to APC in the proband (ratio 1.5) and relatives: father (1.4), brothers (1.5 and 1.5), while the mother was within the normal range (> or = 2). In normal controls and OAT patients the ratio was over 2. No other abnormalities were detected in the assays performed. It is concluded that RAPC is the cause of this familial trombophilia. RAPC should be included in the evaluation study of trombophilia.
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PMID:[Familial thrombophilia due to resistance to activated protein C]. 798 58


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