And/or Antiphospholipid Syndrome Research Articles

Value of second-trimester uterine artery pulsatility index in pregnancies with systemic lupus erythematosus and/or antiphospholipid syndrome

Objective To assess the value of the second trimester mean pulsatility index of the uterine arteries (MPI-UtA) to predict adverse perinatal outcome (APO) in women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Methods Pregnancies with either an SLE diagnosis or with primary APS controlled at our Hospital during a 10 years period were included. MPI-UtA was performed between 19–23 weeks' gestation. The MPI-UtA was defined as abnormal when it was >95th centile. APO was defined as the presence of: preeclampsia (PE), small for gestational age (SGA) newborn, preterm delivery, placental abruption and fetal or neonatal death. Results There were 39 ongoing pregnancies, 16 of them with SLE and 23 with primary APS. Nine patients had no previous pregnancy (23%). Globally, 35 live births were recorded, being the mean gestational age at delivery 38.1 ± 2.1 weeks and the mean birth weight 2835 ± 492 g. Abnormal MPI-UtA was found in 6 (15%) pregnancies, all of them (100%) had an APO: there were 4 fetal deaths and 2 further severe PE with live newborn. Normal MPI-UtA was shown in the remaining 33 (84.6%); of them, 6 (18%) had an APO: one late PE with a premature newborn, another one severe preterm baby and 4 SGA term newborns. No cases of perinatal death occurred in this group. Therefore, accuracy of MPI-UtA evaluation for APO was: sensitivity 50%, specificity 100%, PPV 100% and NPV 82%, respectively (p < .001). Conclusion Abnormal second-trimester uterine artery Doppler evaluation is highly predictive for adverse perinatal outcome in pregnancies affected by SLE or APS.

In Vitro Fertilization in 37 Women with Systemic Lupus Erythematosus or Antiphospholipid Syndrome: A Series of 97 Procedures.

To compile and assess data about complication and success rates for in vitro fertilization (IVF) of women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). To date, such data are sparse. This retrospective study described women with SLE and/or APS who have had at least 1 IVF cycle. Thirty-seven women with SLE (n = 23, including 8 with antiphospholipid antibodies), SLE with APS (n = 4), or primary APS (n = 10) underwent 97 IVF procedures. For 43% of cases, the infertility was female in origin, for 19% male, 14% mixed, and 24% unexplained. No women had premature ovarian insufficiency because of cyclophosphamide. Median age at IVF was 34 years (range 26-46). The median number of IVF cycles was 2.6 (1-8). Patients were treated with hydroxychloroquine (72%), steroids (70%), azathioprine (3%), aspirin (92%), and/or low molecular weight heparin (62%). There were 27 (28%) pregnancies, 23 live births among 26 neonates (3 twin pregnancies), 2 miscarriages, and 2 terminations for trisomy 13 and 21. Six spontaneous pregnancies occurred during the followup. Finally, 26 women (70%) delivered at least 1 healthy child. Complications occurred in or after 8 IVF cycles (8%): SLE flares in 4 (polyarthritis in 3 and lupus enteritis in 1) and thromboembolic events in 4 others. One SLE flare was the first sign of previously undiagnosed SLE. Poor treatment adherence was obvious in 2 other flares and 2 thromboses. No ovarian hyperstimulation syndrome was reported. These preliminary results confirm that IVF can be safely and successfully performed in women with SLE and/or APS.

EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome

ObjectivesDevelop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS).MethodsSystematic review of evidence followed by modified Delphi method to compile questions, elicit...

Clinical significance and correlations between anti-β2 glycoprotein I IgA assays in antiphospholipid syndrome and/or systemic lupus erythematosus

BackgroundThe objective of this investigation was to examine the clinical significance of IgA anti-β2 glycoprotein I (anti-β2GPI) antibodies and the inter-assay relationships between kits for their determination. MethodsSerum samples from 269 patients with clinical diagnoses of systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS), individuals positive for antiphospholipid antibodies (aPL) with or without APS or SLE, and 182 controls were tested for anti-β2GPI IgA antibodies using kits from four manufacturers. ResultsThe positivity rates for the different IgA anti-β2GPI antibody kits varied in the disease groups; 7.8–14.7% (SLE only), 12.0–15.7% (SLE and APS/aPL), 14.7–58.8% (APS only), and 17.4–52.2% (aPL only). Kappa agreements between any 2 kits within disease groups were also variable and ranged from 0.25–1.00 (SLE), 0.18–1.00 (SLE and APS/aPL), 0.22–0.94 (APS only), and 0.32–0.91 (aPL only). Univariate analyses also showed variable relative risks for specific APS clinical manifestations with the different kits evaluated. Overall, diagnostic and predictive values for IgA anti-β2GPI antibodies are kit-dependent; therefore results are not interchangeable. While all 4 kits seem able to predict venous thrombosis tolerably well, there was a variable performance in predicting pregnancy related morbidity. ConclusionsEfforts to standardize these assays are highly needed prior to their formal adoption in routine clinical evaluation.

Decreased diffusion capacity on lung function testing in asymptomatic patients with systemic lupus erythematosus does not predict future lung disease.

In a previous study performed 9 ± 3.6 years ago, 74 asymptomatic patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) underwent lung function testing. A significantly low diffusion capacity (DLCO) ranging from 45% to 70% was recorded in 28 of the 74 (37.8%) patients who were all free of respiratory symptoms. The aim of this report is to assess the clinical importance and the predictive value of a low DLCO in asymptomatic patients with SLE or APS. Asymptomatic patients with SLE and/or APS who were found to have a low DLCO in the previous study were contacted. Of the 28 patients, 15 were recruited and reevaluated in the current study (SLE with APS (n = 7), SLE without APS (n = 7); primary APS (n = 1)). A full history, physical examination, nail bed capillaroscopy, current laboratory tests and full lung function tests including DLCO were performed. During a surveillance period of 9 ± 3.6 years, none of the patients developed lung disease. Diffusion capacity corrected for alveolar volume (DLCO/VA) improved in the study group during this period from 60.4% ± 7.0 to 76.1% ± 11.2 (p < 0.0001). Lung function tests including total lung capacity (TLC) and forced expiratory volume in one second (FEV1) remained within normal limits. Capillaroscopy studies did not reveal changes compatible with scleroderma in any of the patients. Low DLCO findings on lung function testing does not have a positive predictive value for the development of future lung disease in patients with SLE, with or without APS, who are free of respiratory symptoms. Our results suggest that a finding of low DLCO in asymptomatic patients with SLE, with or without APS, does not necessarily require further evaluation and imaging and may improve spontaneously over time. Further studies in a larger group of patients are needed to validate these findings.

Evolution of cardiac dysfunction in patients with antiphospholipid antibodies and/or antiphospholipid syndrome: A 10-year follow-up study

ObjectivesTo describe the evolution of valve involvement and myocardial dysfunction over time in patients with systemic lupus erythematosus (SLE) with or without antiphospholipid antibodies (aPL) and/or antiphospholipid syndrome (APS). MethodsFrom an initial cohort of 150 patients assessed by transthoracic echocardiography 10 years ago, 17 patients with primary APS (PAPS), 23 with SLE-associated APS (SLE/APS), 19 with SLE positive for aPL without APS, and 23 with SLE negative for aPL were re-evaluated in the present echocardiography study. ResultsValvulopathy was detected in 65% of PAPS and 62% of SLE patients with or without aPL. Disease duration [odds ratio (OR), 1.63; 95% confidence interval (CI), 1.13–2.36; p = 0.009 for every 5 years of increase] and presence of SLE/APS (OR, 3.51; 95% CI, 1.27–9.67; p = 0.015) were the only factors associated with the progression of valvular disease in univariate and multivariate analyses. Left ventricular diastolic dysfunction similarly progressed over time, with deceleration time (DT) and isovolumic relaxation time (IVRT) being equally prolonged in each of the four groups (p < 0.05). Right ventricular DT was significantly prolonged in each of the three SLE patient groups (p < 0.001), whereas IVRT increased only in SLE/APS patients (p = 0.040). ConclusionsAmong patients with APS and SLE (with or without aPL), SLE/APS and disease duration were independent factors for valvular disease progression in the present 10-year follow-up echocardiography study. Anticoagulation did not arrest valvular disease progression. Ventricular diastolic dysfunction, primarily of the left ventricle, also progressed over the 10-year period.

Compliance with thromboprophylaxis – a patient satisfaction survey

Pulmonary embolism accounts for 11% of maternal deaths in the UK; frequently risk factors for venous thromboembolism (VTE) were identified. The RCOG now recommends that all pregnant women be appropriately...

Atherogenic Antiphospholipid Antibodies in Antiphospholipid Syndrome

Macrophage uptake of oxidized LDL (oxLDL) plays a critical role in early stages of atherosclerosis. We previously reported that oxLDL forms stable complexes with beta2-glycoprotein I (beta2GPI), and that these complexes were frequently present in the sera of patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). oxLDL/beta2GPI complexes were shown to be antigenic targets for autoantibodies present in APS. To understand the role of autoantibodies in accelerated atherosclerosis of SLE and APS, we investigated the binding characteristics of beta2GPI and oxLDL to mouse macrophages, and the effect of anti-beta2GPI and anti-oxLDL autoantibodies on this macrophage binding. IgM anti-oxLDL antibody (derived from Apoe -/- mouse) showed inhibitory effect on oxLDL binding to macrophages. Although beta2GPI partly inhibited oxLDL binding to macrophages, IgG anti-beta2GPI autoantibody (derived from APS model mouse) showed pro-atherogenic property by promoting the binding of oxLDL/beta2GPI to macrophages.

The second trimester Doppler ultrasound examination is the best predictor of late pregnancy outcome in systemic lupus erythematosus and/or the antiphospholipid syndrome

To examine the predictive value of clinical examination, laboratory tests and Doppler ultrasound examination in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) pregnancies. A prospective study of 116 pregnancies followed in a single tertiary referral centre. Outcomes analysed were fetal/neonatal death and adverse pregnancy outcome. Univariate analysis was performed for: (i) medical and obstetric history; (ii) medical and obstetric clinical examination; (iii) biological data; (iv) Doppler ultrasound examination. Variables significantly associated with the outcomes in the univariate analysis were entered into a logistic regression model. Sixteen out of 116 pregnancies ended in 12 fetal deaths and 4 embryonic losses. Hence, data for 100 pregnancies were analysed. Seven fetal deaths and one neonatal death occurred, associated with abnormal end-diastolic umbilical artery Doppler flow at the second trimester (P < 0.006), a history of thrombophlebitis (P < 0.001) or notched uterine artery and growth restriction at the second trimester (P < 0.002). Multivariate analysis retained abnormal end-diastolic umbilical artery Doppler flow (P = 0.047) and history of thrombophlebitis (P = 0.018) as significant predictors. Thirty-one adverse pregnancy outcomes occurred, associated with notched uterine artery (P < 0.00003), abnormal end-diastolic umbilical artery Doppler flow (P < 0.0006) and fetal growth restriction at the second trimester (P < 0.008), growth restriction (P < 0.00001) and notched uterine artery at the third trimester (P < 0.0008), use of heparin (P < 0.05) and history of thrombophlebitis (P < 0.04). Notched uterine artery at the second trimester remained the only predictor in multivariate analysis (P = 0.001). Results of the second trimester Doppler ultrasound examination are the best predictors for late pregnancy outcome in SLE and/or APS.

Prevalence and clinical significance of anticardiolipin antibodies in patients with type 1 autoimmune hepatitis

There are few case reports on the association between autoimmune hepatitis (AIH) and anticardiolipin antibodies (anti-CLAbs) and/or antiphospholipid syndrome (APLS). We studied the anti-CLAbs prevalence in AIH and other hepatic diseases. We also investigated whether anti-CLAbs are co-factor dependent and which is their avidity since co-factor dependency or increased resistance is associated with APLS. Fifty-nine AIH patients, 228 HCV, 50 HBV, 123 with other non-viral and non-autoimmune liver disorders (nV-nALD) and 267 healthy people were investigated for anti-CLAbs and antibodies against beta-2-glycoprotein I (anti-β 2-GPI). Resistance of IgG anti-CLAbs was evaluated using 2 M urea. IgG anti-CLAbs detected in 39% of AIH, 19.7% of HCV ( p=0.006), 14% of HBV ( p=0.01), 8.1% of nV-nALD ( p=0.000) and 1.1% of healthy ( p=0.000). IgG anti-CLAbs were associated with the presence of cirrhosis and active AIH while their resistance to urea was high. Anti-β 2-GPI was detected in two AIH patients. We demonstrated a significantly higher prevalence of anti-CLAbs in patients with AIH compared to other diseases and healthy people. Anti-CLAbs were associated with AIH stage but no association was found with APLS clinical manifestations (thrombosis, pregnancy morbidity, thrombocytopenia). However, their avidity was comparable with that of APLS indicating the need for prospective studies in order to address whether anti-CLAbs in AIH may contribute to the progression of liver disease or APLS development.

Are oxidized LDL/beta2-glycoprotein I complexes pathogenic antigens in autoimmune-mediated atherosclerosis?

The oxidative modification of low-density lipoprotein (LDL) in the intima of arteries contributes to the initiation and progression of atherosclerotic lesions. We have previously reported that oxidized LDL (oxLDL) interacts with an endogenous plasma protein, β2-glycoprotein I (β2GPI), to form complexes and that the interaction is mediated by oxLDL specific ligands. We have also demonstrated the presence of oxLDL/β2GPI complexes in the blood stream of patients with systemic inflammatory and autoimmune diseases. These findings implicate that oxLDL/β2GPI complexes are possible atherogenic autoantigens. Autoantibodies to oxLDL/β2GPI complexes have been associated with arterial thrombosis. Further, circulating IgG immune complexes containing oxLDL and 2GPI were also detected in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Although many unanswered questions remain about the exact pathogenic mechanism(s) involved, oxLDL/β2GPI complexes may be described as metabolic products relevant in atherogenesis and as significant participants in autoimmune-mediated atherosclerosis.

Polymorphism of beta2-glycoprotein I at codons 306 and 316 in patients with systemic lupus erythematosus and antiphospholipid syndrome.

To determine the frequency of mutations in the phospholipid binding domain of beta2-glycoprotein I (beta2GPI) in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS), and to analyze the clinical correlations of such mutations with thromboembolic complications. Exons 7 and 8 of beta2GPI, which encode for its fifth domain, were amplified by polymerase chain reaction, and the presence of mutations was determined by restriction digestion and single-strand conformation polymorphism analysis. A clinical correlation with these mutations and the presence of antiphospholipid antibodies (aPL), lupus anticoagulant (LAC), anti-beta2GPI antibody, and the development of thromboembolic complications was performed using chi-square and Fisher's exact tests. From a total of 143 patients studied, we found that 5.6% were heterozygous for the mutation at exon 7 (codon 306), and 7.7% were heterozygous for the mutation at exon 8 (codon 316). No homozygous subjects were found for either mutation. No significant correlation between these mutations and the presence of aPL, LAC, or anti-beta2GPI antibodies was found. In patients with SLE (n = 95), 4 of 6 patients with exon 8 mutation had thrombosis, compared with 22 of 82 patients without the mutation (P = 0.043). The prevalence of mutations in the fifth domain of beta2GPI in these patients with SLE and/or APS were similar to those previously reported for the general population. Heterozygosity for either mutation does not influence the incidence of aPL, but in patients with SLE, the mutation at exon 8 may predispose to thrombosis as an independent factor.

Placental isoferritin levels in pregnant patients with systemic lupus erythematosus and/or antiphospholipid syndrome.

Low serum placental isoferritin (PLF), an immunosuppressive cytokine-like protein, was found in women with underlying placento-vascular dysfunction, such as intrauterine growth retardation and preeclamptic toxemia. The possible contribution of this placental product in the assessment of pregnant patients with either systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) was investigated. Seventy-five healthy pregnant women used as controls and 25 preselected pregnant patients with either SLE and/or APS were enrolled in the study. Study patients were in remission during conception and all patients agreed to give 5 ml of venous blood at midgestation. The samples were frozen and analyzed retrospectively. After delivery, pregnancy outcomes were gathered from hospital records. Seventeen (68%) women had uneventful pregnancies and deliveries (normal) whereas 8 (32%) showed pathologic obstetric outcomes. Mean midgestational serum PLF levels were similar in the control and normal outcome groups (87 U/ml), whereas significantly lower levels (37 U/ml) were measured in the pathologic outcome group. Using a cutoff level of 10 U/ml, 85% from the normal outcome group and 15% from the pathologic outcome group were above this threshold level, with 60% specificity and 100% sensitivity. These preliminary data suggest that PLF values may reflect placento-vascular functions. These may represent a predictive biomarker for developing obstetric complications in pregnant women with either SLE and/or APS.