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)

Lupus anticoagulants are a group of antibodies commonly found in patients with autoimmune diseases such as systemic lupus erythematosus. Lupus anticoagulants inhibit phospholipid dependent coagulation and may bind to negatively charged phospholipids. Recent studies have suggested an association between anti-beta 2-glycoprotein I and a lupus anticoagulant, whose activity is frequently dependent on the presence of beta 2-glycoprotein I. Based on these observations, the effect of anti-beta 2-glycoprotein I on the autoactivation of factor XII in plasma was investigated. Autoactivation initiated by the presence of negatively charged phospholipids, but not by sulfatide, was strongly inhibited by immunoaffinity purified anti-beta 2-glycoprotein I. The dose-response curve of anti-beta 2-glycoprotein I was identical with that of a precipitating antibody, showing no inhibition at low and high antibody dilutions and maximal inhibition at an intermediate dilution. At high antibody concentrations, an increased rate of factor XIIa activation was observed. This increase was of the same magnitude as the decreased rate observed in plasma supplemented with the same amount of beta 2-glycoprotein I as in the plasma itself. This confirms the inhibitory effect of beta 2-GP-I on the contact activation and shows that inhibition is effective on the autoactivation of factor XII in plasma. The inhibitory action of beta 2-glycoprotein I was independent of the inhibition caused by the anti-beta 2-glycoprotein I/beta 2 glycoprotein I complex suggesting a synchronized inhibition of factor XII autoactivation by beta 2-glycoprotein I and anti-beta 2-glycoprotein I. The inhibition caused by the antibody is suggested to be caused by a reduced availability of negatively charged phospholipids due to the binding of the anti-beta 2-GP-I/beta 2-GP-I complex. This complex may be a lupus anticoagulant.
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PMID:Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma by beta 2-glycoprotein I and anti-beta 2-glycoprotein I. 748 6

In 1990, three groups simultaneously reported that putative IgG antibodies to anionic phospholipids were either not directed to phospholipids or at least required beta 2-glycoprotein-I (beta 2-GP-I) for reactivity in vitro. During the same year, our group described a patient with "idiopathic' hemolytic anemia with serum and erythrocyte-bound IgM antibodies to phosphatidylcholine later found to be independent of beta 2-GP-I for antigen recognition. Lately, the field has been expanded considerably with: (1) the description of other potential antigens such as prothrombin for some lupus anticoagulants, (2) the finding of crossreactivity between some antiphospholipid antibodies (aPL) with thrombomodulin, (3) the presence of serum antibodies to beta 2-GP-I (anti-beta 2-GP-I) in patients with SLE and thromboses, (4) the findings that the clinical manifestations of APS in SLE patients associate more strongly with anti-beta 2-GP-I than with aPL, (5) our finding of a group of SLE patients with the clinical manifestations of APS, with negative serum aPL, but with positive anti-beta 2-GP-I, (6) the description of a group of patients with the clinical manifestations of APS, without serum aPL, without serological nor clinical evidence of any autoimmune disease, but with IgG anti-beta 2-GP-I, and (7) the observation that serum anti-phosphatidylethanolamine antibodies detected in some patients with APS require kininogen (alone or complexed with the kininogen-binding protein), prekallikrein and/or factor XI for in vitro reactivity. Thus, there are antibodies that may be considered true aPL; other "aPL' require a protein cofactor for their detection in vitro, at least in the case of beta 2-GP-I it would appear that their epitope is present on the protein proper not on the phospholipid, hence these are pseudo aPL, and a third group of related anti-cofactor autoantibodies that are directed to the protein in the absence of phospholipid. Clearly, the term "antiphospholipid syndrome' has become obsolete. We propose the term "Antiphospholipid/Cofactor Syndromes' to cull the various syndromes.
Lupus 1996 Oct
PMID:The concept and classification of antiphospholipid/cofactor syndromes. 890 61

Antiphospholipid antibodies (aPL) are associated with a syndrome of arterial and venous thrombosis and recurrent fetal loss. We have shown that IgG purified from patients with aPL activate vascular endothelial cells (EC), converting the steady-state, non-thrombotic endothelial surface to a pro-thrombotic state. The aPL-activated EC are characterized by the expression of leukocyte adhesion molecules, including ICAM-1, VCAM, and E-selectin. EC activation is dependent upon the presence of beta 2-GP-I, a cofactor necessary for anticardiolipin reactivity. In addition, EC activation is not attributable to endotoxin contamination, Fc receptor interactions, or immune complexes, but rather is the result of the specific anticardiolipin reactivity of the IgG. Endothelial activation by aPL may be an important mechanism by which these antibodies cause a hypercoagulable state.
Lupus 1996 Oct
PMID:Antiphospholipid antibodies activate vascular endothelial cells. 890 77

beta 2-glycoprotein I (beta 2-GP-I) the plasma cofactor for anti-phospholipid antibodies adheres on the endothelial surfaces and can be recognized by anti-beta 2-GP-I antibodies naturally occurring in patients with the anti-phospholipid syndrome. As for the cofactor binding to cardiolipin- or gamma irradiated-plates, the endothelial binding is mediated by the so-called phospholipid binding site, a cationic structure able to react with anionic molecules. Endothelial monolayers appear to represent a substrate able to bind beta 2-GP-I and to present it in a suitable manner in order to allow the binding of anti-beta 2-GP-I beta 2 antibodies. The complex between beta 2-GP-I and the respective antibodies induce an endothelial cell activation as demonstrated by the up-regulation of adhesion molecule expression, the secretion of proinflammatory cytokines and the modulation of arachidonic acid metabolism. Taken together these findings strongly sustain a pivotal role for beta 2-GP-I in allowing antibody deposition on the endothelium and in affecting endothelial cell functions potentially responsible for a procoagulant state.
Lupus 1996 Oct
PMID:Modulation of endothelial cell function by antiphospholipid antibodies. 890 79

Previous studies have shown a cross-reaction between anticardiolipin and anti-oxidized low-density lipoprotein (LDL) antibodies in patients with the antiphospholipid syndrome (APS). The aim was to investigate the existence of a cross-reaction between anti-beta2-glycoprotein-I (beta2-GP-I) and anti-oxidized LDL antibodies in a group of APS patients. Ninety-three patients with APS were included in the study; 47 of these patients were diagnosed as primary APS, while the rest (46 patients) fulfilled criteria for the classification of systemic lupus erythematosus (SLE). All patients were positive for the IgG isotype of anticardiolipin antibodies (aCL). Twelve (26%) SLE-associated APS and 14 (29.7%) primary APS patients had raised concentrations of IgG antibodies to oxidized LDL. There was no correlation between anti-beta2-GP-I and anti-oxidized LDL antibodies. Inhibition experiments showed no cross-reaction either between anti-beta2-GP-I and anti-oxidized LDL antibodies, or between anti-beta2-GP-I and anti-native LDL antibodies. Our study suggests that the presence of both anti-beta2-GP-I and anti-oxidized LDL antibodies in patients with APS is not due to the structural similarity and consequent cross-reaction, and that they are two different populations of antibodies directed against different antigens.
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PMID:Lack of cross-reaction between antibodies to beta2-glycoprotein-I and oxidized low-density lipoprotein in patients with antiphospholipid syndrome. 971 50

It has been suggested that patients with clinical features suggestive of antiphospholipid syndrome but being lupus anticoagulant (LA) and anticardiolipin (aCL) negative, should be tested for antibodies to beta(2) glycoprotein-I (abeta(2)GP-I), a protein involved in the binding of antiphospholipid antibodies (aPL) to phospholipid surfaces. This was investigated in the present study where a total of 385 women aged </=40 years were included. Of these, 175 were experimental subjects and 210 were controls. The former comprised the following two study groups: 100 spontaneous recurrent aborters (group one), and 75 patients with repeated failure of embryo transfer (group two). Controls included three groups of women: 100 normal healthy parous women with no previous abortion (group three), 60 infertile patients achieving a live birth with their first in-vitro fertilization (IVF)/embryo transfer attempt (group four), and 50 patients with recurrent abortion who tested positive for aPL (LA and/or aCL) (positive controls, group five). Only one patient among recurrent aborters (group one) tested positive for abeta(2)GP-I. All women in groups two, three and four were negative for abeta(2)GP-I screening. As expected, prevalence of patients testing positive for abeta(2)GP-I was significantly higher in group five than among the other groups of patients (P < 0.001). No differences were observed regarding the prevalence of abeta(2)GP-I positive sera in the subgroup of patients having aCL and those having the LA in group five. It is concluded that abeta(2)GP-I screening in first-trimester recurrent abortion or in failure of implantation after IVF is not warranted in patients without aPL as detected by standard antiphospholipid assays.
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PMID:Human reproductive failure is not a clinical feature associated with beta(2) glycoprotein-I antibodies in anticardiolipin and lupus anticoagulant seronegative patients (the antiphospholipid/cofactor syndrome) 1073 54

Antiphospholipid antibodies [such as anticardiolipin antibodies (ACLA)] are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories have been advanced. The most common thrombotic events associated with ACLA are deep vein thrombosis and pulmonary embolus (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome) or cerebrovascular/retinal vessel thrombosis (type III syndrome), and occasionally patients present with mixtures (type IV syndrome). Type V patients are those with antiphospholipid antibodies and fetal wastage syndrome. It is as yet unclear how many seemingly normal individuals who may never develop manifestations of antiphospholipid syndrome (type VI) harbor asymptomatic antiphospholipid antibodies. The relative frequency of ACLA in association with arterial and venous thrombosis strongly suggests that these should be looked for in any individual with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed. Also, the type of syndrome (I through VI) should be defined, if possible, as this may dictate both type and duration of both immediate and long-term anticoagulant therapy. Unlike those with ACLA, patients with primary lupus anticoagulant thrombosis syndrome usually suffer venous thrombosis. Because the activated partial thromboplastin time (aPTT) is unreliable in patients with lupus anticoagulant (prolonged in only about 40 to 50% of patients) and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests including ELISA for ACLA, the dRVVT for lupus anticoagulant, hexagonal phospholipid neutralization procedure, and B-2-GP-I (IgG, IgA, and IgM) should be immediately ordered when suspecting antiphospholipid syndrome or in individuals with otherwise unexplained thrombotic or thromboembolic events. If these are negative, in the appropriate clinical setting, subgroups should also be assessed. Finally, most patients with antiphospholipid thrombosis syndrome will fail warfarin therapy and, except for retinal vascular thrombosis, most will fail antiplatelet therapy, thus it is of major importance to make this diagnosis in order that patients can be treated with the most effective therapy for secondary prevention, low-molecular weight heparin (LMWH) or unfractionated heparin (UHF) in most instances.
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PMID:Antiphospholipid syndrome and thrombosis. 1044 63

Antiphospholipid antibodies are strongly associated with thrombosis and are the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagutable state remain unclear, numerous theories, as previously discussed, have been advanced. The most common thrombotic events associated with anticardiolipin antibodies are deep vein thrombosis and pulmonary embolus (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome), or cerebrovascular/retinal vessel thrombosis (type II syndrome); occasionally, patients present with mixtures of these types (type IV syndrome). Type V patients are those with antiphospholipid antibodies and RMS. It is as yet unclear how many seemingly normal individuals who may never develop manifestations of antiphospholipid syndrome (type VI) harbor asymptomatic antiphospholipid antibodies. The relative frequency of anticardiolipin antibodies in association with arterial and venous thrombosis strongly suggests that these should be looked for in any individual with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed. Also, the type of syndrome (I through VI) should be defined if possible, as this may dictate both type and duration of both immediate and long-term anticoagulant therapy. Unlike those with anticardiolipin antibodies, patients with primary lupus anticoagulant thrombosis syndrome usually experience venous thrombosis. Because the aPTT is unreliable inpatients with lupus anticoagulant (prolonged in only about 40 to 50% of patients) and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests, including ELISA for anticardiolipin antibodies, the dRVVT for lupus anticoagulant, hexagonal phospholipid neutralization procedure, and beta-2-GP-I (IgG, IgA, and IgM) should be immediately ordered when suspecting antiphospholipid syndrome or in individuals with otherwise unexplained thrombotic or thromboembolic events. If results of these tests are negative, in the appropriate clinical setting, subgroups should also be assessed. Finally, most patients with antiphospholipid thrombosis syndrome will fail warfarin therapy and, except for retinal vascular thrombosis, may fail some types of antiplatelet therapy; thus it is of major importance to make this diagnosis so that patients can be treated with the most effective therapy for secondary prevention--LMWH or UH in most instances, and clopidogrel in some instances.
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PMID:Antiphospholipid thrombosis syndromes. 1169 5

Antiphospholipid antibodies (aPL) are immunoglobulins of IgG, IgM and IgA isotypes that target phospholipid (PL) and/or PL-binding plasma proteins. Detection of aPL in the laboratory is done currently by both immunoassays and functional coagulation tests. Convention defines aPL specificity in immunoassays according to the particular PL substrate present, for example aPS represents antiphosphatidylserine antibodies. This may be technically incorrect inasmuch as a particular PL may be responsible for binding and highly concentrating a specific plasma protein, the latter then becomes the target for the aPL. The binding of beta(2)GP-I (apolipoprotein H) to the negatively charged PL, cardiolipin (CL) provides a good example of this circumstance. In contrast, aPL which specifically prolong coagulation times in in vitro are called lupus anticoagulants (LA). The precise PL target(s) of the aPL responsible for LA activities are unknown and often debated. The persistent finding of aPL in patients in association with abnormal blood clotting and a myriad of neurological, obstetrical and rheumatic disorders often compounded by autoimmune diseases has led to an established clinical diagnosis termed antiphospholipid syndrome (APS). The common denominator for these APS patients is the presence of circulating aPL on two or more occasions and the observation of events attributable to abnormal or accelerated blood clotting somewhere in vivo. The purpose of this review is to collect, collate, and consolidate information concerning aPL.
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PMID:Antiphospholipid antibodies: discovery, definitions, detection and disease. 1268 18

Venous or arterial thrombosis, abortion, and the presence of antiphospholipid antibodies (aPL) define the criteria for the antiphospholipid syndrome (APS). A heterogeneous group of antibodies against phospholipids and plasma proteins may influence several coagulation pathways and lead to thrombophilia. We investigated the presence of antibodies to thrombin (Thr) in patients with aPL and reviewed their clinical manifestations. IgG and IgM titers of aPL were measured by ELISA (Aesku.Diagnostics, Wendelsheim, Germany). Lupus anticoagulants (LA) were measured according to the criteria of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. One hundred twenty patients were identified with LA or anticardiolipin (aCL). Of the 120 patients, 98 (82%) had primary APS and 22 (18%) had secondary APS. Further, 76/120 (63%) were suffering from thromboembolic manifestations, mostly venous thrombosis. Anti-thrombin-IgG was detected in 20%, and anti-thrombin-IgM was detected in 23% of the patients. The presence of anti-thrombin antibodies was closely related to the presence of anti-beta(2)-glycoprotein-I (beta(2)-GP-I) (96%), aCL (97%), and LA (87%), and less well to the presence of anti-phosphatidylserine/prothrombin (Ser/Pro) antibodies (71%) or anti-prothrombin antibodies (Pro) (50%). Sixty-seven percent of the patients with anti-Thr-IgG suffered from thromboembolic complications, mostly arterial thrombosis. The rate of thrombosis was higher for these patients than for patients with anti-beta(2)-GP-I antibodies (37/60, 62%), LA (50/79, 63%), or anti-Ser/Pro antibodies (18/28, 64%). Anti-thrombin antibodies were found in 20% of patients with aPL; 67% of these patients were admitted with thrombotic manifestations of APS. The presence of anti-thrombin antibodies was closely associated with the presence of aCL and anti-beta(2)-GP-I antibodies. The sensitivity of the test for anti-thrombin antibodies for the diagnosis of APS was higher than the sensitivity of the anti-prothrombin assay and similar to the sensitivity of the anti-Ser/Pro assay.
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PMID:Identification of thrombin antibodies in patients with antiphospholipid syndrome. 1601 40


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