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)

Several therapeutic regimens have been proposed for women with recurrent spontaneous abortion (RSA) and antiphospholipid antibodies (APA). Conflicting results have been reported about women with history of RSA, positive APA, and failure of standard therapy. To evaluate the use of intravenous immunoglobulin in RSA patients with APA and history of treatment failure, we initiated a study with standard therapy (aspirin and low-molecular-weight heparin) and intravenous immunoglobulin. We used an enzyme-linked immunosorbent assay (ELISA) test to screen IgG and IgM anticardiolipin antibodies, and a diluted Russel viper venom time assay for the lupus anticoagulant activity. Altogether, 66 pregnant women with positive APAs at the first visit could be included. Patients with hereditable thrombophilic factors were excluded. After confirmation of the pregnancy, women received a basis immunization of 0.3 g/kg immunoglobulin in a 4-week cycle until the 28th to 32nd week of gestation. All patients received 100 mg/d aspirin and 3,000 anti-Xa U/d certoparin. Among the 66 pregnant women, 17 were persistently autoantibody positive (25.8%), of whom 11 (16.7%) were ACA positive alone, 2 (3%) were lupus anticoagulant positive, and 4 (6.4%) had both antibody types. A total of 49 patients had positive APAs at the initial test, but were negative for ACA and lupus anticoagulant at the second test administered approximately 5 weeks after the start of therapy. We described this group in our following observation as "antibody negative." Sixteen of the 17 autoantibody-positive patients (94.1%) were delivered of live infants compared with 40 patients (81.6%) in the antibody-negative group (odds ratio [OR]: 1.2; 95% CI: 0.98 to 1.4). The overall miscarriage rate was 12.1% and the fetal loss rate was 15.2%. Four patients (25%) in the antibody-positive group developed symptoms of preeclampsia and fetal growth retardation compared with four patients (9.8%) in the antibody-negative group. In conclusion, we see a reduction of the fetal loss rate in patients with RSA and positive APA (5.8%) compared with APA-negative (18.4%) women with the same therapy (OR: 0.3; 95% CI: 0.04 to 2.3).
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PMID:The influence of antiphospholipid antibodies on the pregnancy outcome of patients with recurrent spontaneous abortion. 1169 9

The presence of antiphospholipid antibodies, lupus anticoagulant and anticardiolipin antibody in patients with systemic lupus erythematosus has been associated with the clinical features of thrombosis, fetal loss and thrombocytopenia, and the syndrome is designated as antiphospholipid antibody syndrome (APS). APS has been increasingly diagnosed in patients without underlying autoimmune disease and is most frequently seen in obstetric patients suffering spontaneous abortion, preeclampsia and intrauterine growth restriction. The hypothesis underlying most research into the pathophysiology of APS is that autoantibodies are not only the markers of the disease, but also directly contribute to the development of clinical features. This review summarizes recent information on the pathophysiology and potential roles of autoantibodies in the obstetric patients suffering, particularly in the subgroup of repeated spontaneous abortions.
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PMID:Antiphospholipid antibody syndrome and fetal outcome. 1185 31

The case of an apparent healthy woman who developed recurrent preeclampsia with antiphospholipid antibodies and evolved towards systemic lupus erythematosus during her last pregnancy is presented. The diagnostic dilemma between lupus renal flare and toxemia is discussed. The potential role of immunological alterations, such as complement genetic deficiencies, in women with primary antiphospholipid syndrome who develop systemic lupus erythematosus is also discussed.
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PMID:C4 deficiency state in antiphospholipid antibody-related recurrent preeclampsia evolving into systemic lupus erythematosus. 1211 Oct 90

Antiphospholipid syndrome is defined by recurrent thrombotic events and fetal losses in the presence of anti-phospholipid antibodies detectable by beta 2 glycoprotein I-dependent anti-cardiolipin and/or lupus anticoagulant assays. Thrombosis can occur in any vascular district but deep veins and cerebral arteries represent the most frequent sites. Both early and late fetal losses have been reported in women affected by the syndrome as well as pre-eclampsia. Beta 2 glycoprotein I-dependent anti-cardiolipin and lupus anticoagulant are the formal laboratory diagnostic tools; new assays appear to improve the diagnostic power, but larger validation studies are needed before accepting them on a routine basis. In spite of the improvement in our knowledge on the pathogenic mechanisms of the syndrome, the standard therapy is still based on anti-platelet or anticoagulant drugs both for vascular and obstetrical problems.
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PMID:Up-date on the antiphospholipid syndrome. 1224 62

Anti-Ro/SSA antibodies are associated with neonatal lupus but are also considered a possible cause for unexplained pregnancy loss and adverse pregnancy outcome. In a large multicentres cohort study we have prospectively followed 100 anti-Ro/SSA positive women (53 systemic lupus erythematosus (SLE)) during their 122 pregnancies and 107 anti-Ro/SSA negative women (58 SLE) (140 pregnancies). Anti-Ro/SSA antibodies were tested by immunoblot and counterimunoelectrophoresis. Mean gestational age at delivery (38 vs 37.9 weeks), prevalence of pregnancy loss (9.9 vs 18.6%), preterm birth (21.3 vs 13.9%), cesarean sections (49.2 vs 53.4%), premature rupture of membranes (4.9 vs 8.1%), preeclampsia (6.6 vs 8%), intrauterine growth retardation (0 vs 2.3%)and newborns small for gestational age (11.5 vs 5.8%) were similar in anti-Ro/SSA positive and negative SLE mothers; findings were similar in non-SLE women. Two cases of congenital heart block were observed out of 100 anti-Ro/SSA positive women. In conclusion, anti-Ro/SSA antibodies are responsible for congenital heart block but do not affect other pregnancy outcomes, both in SLE and in non-SLE women. The general outcome of these pregnancies is now very good, ifprospectively followed by multidisciplinary teams with ample experience in this field.
Lupus 2002
PMID:Pregnancy outcome in 100 women with autoimmune diseases and anti-Ro/SSA antibodies: a prospective controlled study. 1247 1

Preeclampsia/HELLP syndrome has been associated with a high incidence of defects in the protein C pathway and increased anticardiolipin-antibodies/lupus anticoagulants. It is also apparent that thrombophilia is responsible for other pregnancy complications, such as recurrent spontaneous abortion, fetal growth restriction, intrauterine fetal death, and abruptio placentae. ProC Global is a new global dotting assay designed to evaluate the abnormalities in the protein C anticoagulant pathway. It is based on the ability of endogenous activated protein C, generated by activation of protein C by Protac, to prolong an activated partial thromboplastin time. A total of 61 patients with a history of severe preeclampsia or HELLP syndrome and 61 normal pregnant women (controls) were evaluated, 15 of whom had factor V Leiden mutation, 12 had protein C/S deficiency, 30 had a repeated lupus anticoagulants, and 27 increased anticardiolipin antibodies (ACA). All carriers of factor V Leiden mutation (N=15) as well as all the patients with low activated protein C (APC) resistance ratio (N=15) had a ProC Global normalized ratio (NR) less than 0.80 (sensitivity 100%). Twenty-four patients positive for the lupus anticoagulants (LA) and 19 patients positive for ACA (>5.0 IgG U/mL) had a ProC Global NR less than 0.8, while six and eight, respectively, had a ProC Global NR greater than 0.8 (sensitivity, 70%-80%). The detection of a reduced protein C/protein S activity (<70%) was low (sensitivity, 33%-44%). In 25 cases with pathologic ProC Global results, a thrombophilic defect (protein S/LA/ACA without APC resistance) was diagnosed in 18 women; but in 7 cases, no known thrombophilic defect was present. ProC Global is a new screening test to identify patients with defects of the protein C system and an activated dotting system in preeclampsia but cannot correctly cover each thrombophilic component.
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PMID:ProC Global assay in the evaluation of women with history of severe preeclampsia or HELLP syndrome. 1251 22

Antiphospholipid (aPL) antibodies (i.e., lupus anticoagulants and anticardiolipin [aCL] antibodies) are associated with obstetric complications. Recurrent spontaneous abortions and fetal death represent the obstetric criteria of the aPL syndrome. Intrauterine growth retardations, preeclampsia, and prematurity are other common clinical features not included in the syndrome. Overall, the prevalence of obstetric complications in aPL-positive women is about 15 to 20%. The presence of lupus anticoagulants carries a risk of recurrent miscarriages and fetal death ranging from and odds ratio of 3.0 to 4.8, whereas that of aCL antibodies ranges from 0.86 to 20. The mechanism(s) by which aPL antibodies causes these events still has to be defined. Thrombosis in the placental vessels, which causes placental hypoxia and eventually leads to abortion or fetal death, has been reported in aPL-positive women with obstetric complications. Impairment of embryonic implantation has also been proposed. Unfractionated or low-molecular-weight heparins, alone or in combination with low-dose aspirin, represent the current standard treatment of pregnant aPL-positive women to prevent recurrent obstetric complications. Upon treatment, the live birth rate increases from 0 to 40% to 70 to 80%. Despite these good results, heparin-treated pregnancies are still characterized by an excessive frequency of maternal and/or fetal complications, indicating the necessity of a better calibration of the dosage, duration, and timing of administration of heparin treatment.
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PMID:Antiphospholipid syndrome: definition and treatment. 1270 23

Starting from their first description, antiphospholipid antibodies (aPL) were associated with repeated miscarriages and fetal losses. Other complications of pregnancy like preterm birth,with pre-eclampsia or severe placental insufficiency were also frequently reported and are included in the current classification criteria of the antiphospholipid syndrome (APS). The titre, the isotype of the antibodies or their antigen specificity may be important in the risk level determination. Some of the difference in the reported results can be explained by the poor standardization achieved in aPL testing or by the not univocal classification of pregnancy complications. The pathogenesis of pregnancy failures is linked to the thrombophilic effect of aPL but also to different mechanisms including a direct effect of antibodies on the throphoblast differentiation and invasion. The study of experimental animal models provided sound evidence of the pathogenic role of aPL both in lupus prone and naive mice. The definition of APS as a condition linked to high obstetric risk and the application of an effective therapy have completely changed the prognosis of pregnancy in these patients. In fact, despite the high number of complications and preterm delivery, today a successful outcome can be achieved in the large majority of the cases.
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PMID:Pregnancy complications of the antiphospholipid syndrome. 1276 68

Pregnancy markedly alters a normal woman's physiology and immune response mechanisms. The effect of pregnancy changes on the course of systemic lupus erythematosus (SLE) remains, however, speculative. Pregnant lupus patients are susceptible to pre-eclampsia, especially if they suffer lupus nephritis, and to steroid-induced hypertension and hyperglycemia. Fetuses are susceptible to placental insufficiency if antiphospholipid antibody or other procoagulant states are present, and to neonatal lupus if anti-Ro/La antibodies are present. Artificial reproductive technologies ("in vitro fertilization") can be safely used in SLE patients. Study of the physiology of pregnancy, for instance complement kinetics, may inform our understanding of SLE, and vice versa.
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PMID:Lupus pregnancy. 1276 69

The classical clinical picture of the antiphospholipid syndrome (APS) is characterized by venous and arterial thromboses, fetal losses and thrombocytopenia, in the presence of antiphospholipid antibodies (aPL), namely lupus anticoagulant (LA), anticardiolipin antibodies (aCL), or antibodies to the protein "cofactor" b2 glycoprotein I. Single vessel involvement or multiple vascular occlusions may give rise to a wide variety of presentations. Any combination of vascular occlusive events may occur in the same individual and the time interval between them also varies considerably from weeks to months or even years. Deep vein thrombosis, sometimes accompanied by pulmonary embolism, is the most frequently reported manifestation in this syndrome. Cerebrovascular accidents-either stroke or transient ischemic attacks-are the most common arterial thrombotic manifestations. Early and late fetal losses, premature births and pre-eclampsia are the most frequent fetal and obstetric manifestations. Additionally, several other clinical features are relatively common in these patients, i.e., thrombocytopenia, livedo reticularis, heart valve lesions, hemolytic anemia, epilepsy, myocardial infarction, leg ulcers, and amaurosis fugax. However, a large variety of other clinical manifestations have been less frequently described in patients with the APS, with prevalences lower than 5%. These include, among others, large peripheral or aortic artery occlusions, Sneddon's syndrome, chorea, transverse myelopathy, intracardiac thrombus, adult respiratory distress syndrome, renal thrombotic microangiopathy, Addison's syndrome, Budd-Chiari syndrome, nodular regenerative hyperplasia of the liver, avascular necrosis of the bone, cutaneous necrosis or subungual splinter hemorrhages. In this article, some of these "unusual" manifestations are reviewed.
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PMID:Unusual manifestations of the antiphospholipid syndrome. 1279 62


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