High incidence of anticardiolipin antibodies in relatives of patients with systemic lupus erythematosus

Anticardiolipin antibodies (aCL) were measured in the serum of 22 patients with systemic lupus erythematosus (SLE) and 101 of their first degree relatives. Four patients' sera (18%) were positive. Eight sera from relatives were strongly positive (7.9%). All 8 relatives came from different families, and only 3 of them were related to a positive positive proband. All 8 had clinical and/or other serological abnormalities, compared with only 30% of the aCL negative relatives (p less than 0.05). There were no reports or evidence of thrombosis, thrombocytopenia or spontaneous abortion among the aCL positive relatives. Our data indicate a strikingly higher incidence of aCL among relatives of lupus patients compared with controls. This may be associated with an increased incidence of abnormal clinical or serological findings in these individuals, and constitute a feature of a genetic predisposition to SLE.     

Cardiolipin antibodies and null alleles of C4 in black Americans with systemic lupus erythematosus

Twelve of 44 black American patients with systemic lupus erythematosus (SLE) (27%) studied during periods of disease activity had increased levels of IgG antibodies against cardiolipin (IgG aCL). IgG aCL occurred almost exclusively in patients who had a partial genetic deficiency of C4A or C4B. Eleven of 29 patients (38%) with a C4A or C4B deficiency allele had IgG aCL, compared with 1/15 patients (7%) who did not have C4A or C4B deficiency allele (p = 0.04). During periods when SLE was less active clinically, IgG aCL levels returned to normal in 10/12 patients. Active SLE, rather than null alleles, appeared to be associated with low C4 levels in patients with IgG aCL.     

Cardiovascular disease in systemic lupus erythematosus. A study of 75 patients form a defined population.

All patients with systemic lupus erythematosus in a prospective, epidemiologically based study within a defined area in southern Sweden were invited to participate in an investigation of cardiac function. From 1981 to 1988, 101 patients were included in the study, and 75 of them were investigated according to a fixed protocol by echocardiography, Doppler cardiography, electrocardiography (ECG) at rest and at exercise, and myocardial scintigraphy (in patients whose ECG became abnormal during exercise). IgG anticardiolipin antibodies (IgG aCL) were determined by ELISA. Twenty of the 75 patients (27%) had valvular disease and 12 of these (60%) had increased concentrations of IgG aCL, compared with 12 of 55 (22%) without valvular disease (p less than 0.01). Pericardial effusion was detected in 14 patients (19%) during the study period. Mild pulmonary hypertension was found in 11 patients (16%), who also had increased frequency of IgG aCL. Myocardial infarction had occurred in 7 patients, 3 of whom were women less than 40 years of age. Echocardiography revealed regional hypokinesis or akinesis in 5 of the patients with myocardial infarction. Exercise testing revealed low work capacity in 13 of 54 patients (24%), the limiting symptoms being mainly exhaustion or musculoskeletal pain. An abnormal resting ECG was found in 9 of the patients participating in the exercise test. During exercise, abnormal ST-depression was observed in 8 patients, 2 of whom developed angina. Myocardial scintigraphy was performed in 6 of these patients, revealing reversible uptake defects in all. Prolonged glucocorticoid treatment was associated with valvular abnormalities as well as myocardial infarction. Valvular abnormalities and IgG aCL appeared to be risk factors for cerebral infarction.     

Beta2 glycoprotein 1 in Indian patients with SLE.

Forty-five patients with systemic lupus erythematosus (SLE) were investigated to evaluate the role of antiphospholipid antibodies in causation of thrombosis in Indians. The antiphospholipid antibodies studied included lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and anti-beta(2)-glycoprotein 1 (a beta(2)-GP1). Twenty-seven patients (60%) had clinical manifestations of antiphospholipid antibody syndrome. Nineteen patients (42.2%) had a history of thrombosis, and eight (17.7%) had a history of recurrent fetal loss. aBeta(2)-GP1 was (IgG) was positive in 23 (51.1%), aCL in 13 (28.8%), and LAC in four (8.8%). Of 19 patients with thrombosis, 14 (73.6%) were positive for abeta(2)-GP1, eight (42.1%) for aCL, and none of them was positive for LAC. Of the eight patients with recurrent fetal loss, two (25%) patients were positive for beta(2)-GP1, five (62.5%) for aCL, and one (12.5%) for LAC. Of 18 patients without any manifestations of antiphospholipid syndrome (APS), seven patients (38.8%) were positive for abeta(2)-GP1, and three (16.6%) for aCL and LAC each. It is concluded that presence of abeta(2)-GP1 increases the risk of thrombosis and therefore should be looked for in all cases of SLE to consider prophylactic antithrombotic therapy in these patients.     

The place of beta 2 glycoprotein 1 in the assessment of antiphospholipid syndrome.

beta 2 glycoprotein 1 (beta2GP1) is a phospholipid-binding protein implicated in the development of antiphospholipid antibodies, associated with thromboembolic complications and fetal morbidity and death, and is thought to corrrelate better than anticardiolipin (aCL) assays. We analysed the role of beta2GP1 in assessing 86 patients being investigated for antiphospholipid syndrome. Thirty-nine patients had 3 tests: [lupus anticoagulant (LA), aCL and beta2GP1], and a further 46 had aCL and beta2GP1. Sixty-one patients had completely negative tests. Five patients had beta2GP1 as the only positive result. 80% of this group had recurrent miscarriage suggesting that beta2GP1 may be an useful adjunct to aCL and LA testing in patients with a significant obstetric history.     

The prevalence of vascular occlusive disease associated with antiphospholipid syndromes.

The association of anticardiolipin antibodies (aCL) with unexplained vascular occlusive disease (VOD) is well known. We reviewed the records of 102 consecutive patients seen over a 9 months period who had positive IgG or IgM aCL to determine the frequency and types of VOD in this unselected group of patients. Lupus anticoagulant was detectable in 17 of 67 (25%) patients tested. VOD occurred in 80 of 102 (78%) aCL-positive patients comprised of 17 (16.7%) with systemic venous VOD or pulmonary embolism; 27 (26.5%) with cerebral VOD: 11 (10.8%) with systemic arterial VOD; 3 (2.9%) with coronary thrombosis; and 5 (4.9%) with visceral venous or arterial VOD. Of the 19 obstetric patients with positive aCL, 17 (89%) had at least one unexplained fetal loss and 8 of the 17 (47%) had multiple or recurrent fetal losses. Twelve (11.7%) of the 102 patients met the ACR criteria for systemic lupus erythematosus (SLE). Additionally, 12 (11.7%) patients were identified as nonSLE or undifferentiated connective tissue disease (CTD). The remaining 78 (76%) had no known underlying disease (primary antiphospholipid syndrome). We conclude that IgG and IgM aCL with or without lupus anticoagulant are associated with diverse types of VOD but cerebral VOD appears predominant. aCL-associated unexplained VOD occurs frequently in patients without evidence of CTD-65 of 80 (81%) in our series. Testing for aCL is essential for identifying patients with unexplained VOD, and it should be performed in prospective clinical studies of such patients to better define the pathogenic role of aCL in the natural history of unexplained VOD.     

Anti-annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody

We investigated anti-annexin V antibody (aANX) in patients with systemic lupus erythe-matosus (SLE), and correlated to positivity with lupus anticoagulant (LA)/anticardiolipin antibody (aCL). aANX was positive in 12/47 SLE patients (26%), including 7 with β₂-glycoprotein 1 (GPl)-dependent aANX. The positivity of aANX was higher in patients with aCL (19%) and LA/aCL (50%) than in those without LA/aCL (10%). From these results, it is concluded that aANX is an autoantibody closely related to LA/aCL, and can be a possible new risk marker for thrombosis. © 1994 Wiley-Liss, Inc.     

Comparison of different kits in the detection of autoantibodies to cardiolipin and beta2glycoprotein 1

OBJECTIVE: To estimate the performance characteristics of 10 commercial kits and one in-house kit for the detection and quantification of anticardiolipin (aCL) (six kits) and anti-beta2glycoprotein 1 (anti-beta2GP1) (five kits) antibodies, and to evaluate the degree of variability between these different kits. METHODS: We determined the presence of aCL and anti-beta2GP1 IgG and IgM antibodies in 67 sera from 62 patients and reviewed the data separately. Each serum sample was tested with six commercial aCL determination kits and with four commercial and one in-house anti-beta2GP1 determination kit. We then analysed the operating characteristics of each kit (sensitivity, specificity, positive and negative predictive values) and we analysed the absolute and 2 x 2 agreements. RESULTS: The 62 patients included had primary antiphospholipid syndrome (APS) in 10 cases, secondary APS for eight, systemic lupus (SLE) for 23 and other diagnoses for the remaining 21. Operating characteristics differed from one kit to another. Good agreement was found using sensitive aCL determination kit and specific anti-beta2GP1 determination kit. Agreement between kits was medium for IgG aCL. 2 x 2 concordance studies showed a group of three aCL kits which were quite homogenous and showed that all anti-beta2GP1 kits formed quite a homogenous group. CONCLUSION: A high degree of variability still persists for aCL antibody determination posing the question of the qualification of commercial or in-house kits and the question of standardization of results. A better concordance is found for high positive results. Good agreement exists for anti-beta2GP1 kits. aCL determination is still needed and should be complemented by anti-beta2GP1 determination.     

Anticardiolipin and anti-beta2glycoprotein-I antibodies in patients with systemic lupus erythematosus: comparison between Colombians and Spaniards

We studied the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta2glycoprotein I (anti-beta2GPI) antibodies in two populations of patients with systemic lupus erythematosus (SLE), 160 Colombians and 160 Spaniards. All sera were tested in our laboratory by enzyme-linked immunosorbent assay (ELISA) for IgG, IgM, and IgA aCL, as well as IgG and IgM anti-beta2GPI. Positive results for at least 1 of the 3 aCL isotypes were found in 40 Colombians (25%) and 55 Spaniards (34%). IgG aCL was the predominant isotype in both populations. Positive results for at least 1 of the anti-beta2GPI isotypes were found in 34 Colombians (21%) and 29 Spaniards (18%). IgG anti-beta2GPI was the dominant isotype in Colombians, while IgM was predominant in Spaniards. Positivity for anti-beta2GPI in aCL-positive patients was present in 77% in the Colombian group and 50% in the Spaniard group. Among Colombians, IgG aCL and anti-beta2GPI correlated with thrombosis, fetal loss, and thrombocytopenia. Among Spaniards, IgG aCL and IgG anti-beta2GPI correlated with thrombosis, fetal loss, and livedo reticularis. For detecting thrombosis and fetal loss, aCL ELISA was more sensitive than anti-beta2GPI in Spaniards, and anti-beta2GPI ELISA was more specific than aCL in both populations.     

Clinical and serological risk factors of systemic lupus erythematosus outcomes during pregnancy

IntroductionSLE is an important risk factor for mother and fetus during pregnancy.Aim of the workTo identify clinical and serological risk factors that may cause poor maternal and fetal outcomes in pregnant systemic lupus erythematosus (SLE) patients.Patients and methodsForty selected SLE pregnant women (group A) versus 35 non-pregnant SLE patients (group B). SLE disease activity index (SLEDAI) and flares were evaluated for both groups. Laboratory investigations included double stranded DNA, anticardiolipin antibodies (aCL), and complements (C3 & C4). SLE pregnant patients were followed up in the second and third trimesters by ultrasonography and fetal Doppler were done to assess fetal outcome. Risk factors for poor maternal and fetal outcome were recorded.ResultsSLEDAI was increased in both groups more in group A. Lupus flares were increased during pregnancy as it occurred in (62.5%) of group A compared to (37.14%) in group B where severe flares were more frequent in group A. Gestational hypertension and active SLEDAI were found statistically significant for poor maternal outcome. Fetal outcome included full term 37.5%, prematurity 25%, intra-uterine growth retardation (IUGR) 22.5%, stillbirth 12.5%, abortion 7.5% and congenital heart block (CHB) 2.5%. Factors significantly associated with poor fetal outcome were severe flares and active renal disease where fetal loss significantly associated with aCL antibodies. Full term was more common in patients with no flares.ConclusionThese data demonstrate that pregnancy in SLE patients should be considered as a high-risk pregnancy and conception should be planned during a quiescent period. Close monitoring for optimal disease control of flares, lupus nephritis, gestational hypertension and aCL antibodies is recommended.     

Specificity and sensitivity of anti-beta2-glycoprotein I as compared with anticardiolipin antibody and lupus anticoagulant in Thai systemic lupus erythematosus patients with clinical features of antiphospholipid syndrome

Antibodies to beta(2)-glycoprotein I (anti-beta(2)-GPI) have been reported to have stronger association with clinical antiphospholipid syndrome (APS) than anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). We investigated the sensitivity and specificity of ELISA for anti-beta(2)-GPI in Thai systemic lupus erythematosus (SLE) patients with clinical features of APS and compared the results with IgG/IgM aCL and LAC to find the test with the best association. The hospital records of 151 Thai SLE patients whose sera had been sent for either IgG/IgM anticardiolipin antibodies or lupus anticoagulant testing were reviewed. Sera of patients either without complete clinical records or those with APS-related manifestations other than vascular thrombosis and pregnancy morbidity (according to the international consensus statement on preliminary classification criteria for definite APS) were excluded. For the remaining subjects (112 patients), their sera were tested for anti-beta(2)-GPI antibody, IgG and IgM anticardiolipin, and lupus anticoagulant. The sensitivity and specificity of each method were compared by using the chi-square test. Among the 112 (74.2%) SLE patients in the study, 35 (31.3%) presented with preliminary clinical criteria for APS (i.e., vascular thrombosis and pregnancy morbidity) whereas 77 (68.7%) did not. The sensitivity and specificity of anti-beta(2)-GPI determination were 57.1 and 79.2%, respectively, whereas those of IgG aCL were 25.7 and 94.8%, of IgM aCL were 5.7 and 98.7%, and of LAC were 44.8 and 77.3%, respectively. The accuracy of the four tests showed similar association with clinical APS (accuracy of test = 72.3, 73.2, 69.6, and 68.3%, respectively). Concerning the sensitivity, specificity, and difficulty of the methods, the combination of anti-beta(2)-GPI and IgG aCL tests was the best for the diagnosis of APS in Thai SLE patients.     

Longitudinal study of antinuclear and anticardiolipin antibodies in pregnant women with systemic lupus erythematosus and antiphospholipid syndrome

The objective of this study was to perform a longitudinal follow-up of antinuclear antibodies (ANAs) and anticardiolipin antibodies titers (aCL) throughout pregnancy in a group of patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) patients during their therapy for the prevention of fetal loss and to examine their relationship with pregnancy outcome. Thirty patients and 15 controls were followed in the study. Fifteen patients had SLE (group I) and 15 had APS (group II, of which seven patients had primary APS and eight had APS secondary to SLE). All patients were receiving therapy for the prevention of fetal loss with prednisone and aspirin as part of an ongoing clinical trial in lupus pregnancy. If there was a history of previous thrombosis, heparin was added. Blood samples were taken at the 1st, 2nd, and 3rd trimesters (T) of pregnancy in order to assess the presence of IgG and IgM aCL antibodies (ELISA), anti-dsDNA ( C. luciliae) ANAs (HEp-2 cells), and immunospecific antibodies (antiextractable nuclear antigens). We collected 90 samples from patients and 45 samples from healthy controls. Group I (SLE) ANAs were positive in 100% during the 1st T, 67% in the 2nd T, and 67% in the 3rd T, with various immunofluorescence patterns. In five patients, aCL antibodies were detected without a history of APS (one in 1st T, three in 2nd T, and one in 3rd T). Fetal loss was observed in two patients, in one of whom it was associated with nephritis, high titers of ANAs, and anti-dsDNA. Another patient had pulmonary hemorrhage with anti-dsDNA and aCL. In group II, all but one patient with primary APS were negative to ANAs. In secondary APS, by contrast, 6/8 patients (75%) had positive ANAs at least during the 1st T. All seven patients with primary APS and 6/8 with secondary APS had aCL during pregnancy. In 9/15 (60%) patients from the APS group with a history of previous fetal loss, aCL became negative during pregnancy and they had live births. The disappearance of aCL was associated with improved fetal survival (relative risk, or RR, 0.67). ANAs in the control group were positive in 7% at low titers, and all of them were negative for aCL. Despite treatment, ANAs are prevalent during pregnancy in SLE patients and APS secondary to SLE. During pregnancy in SLE, aCL titers may appear. Decreasing titers and/or disappearance of aCL correlated with improved fetal prognosis in a subset of patients with APS.     

Antiphospholipid syndrome: definition and treatment

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.     

Antiphospholipid antibodies in systemic lupus erythematosus: evidence of an association with positive Coombs' and hypocomplementemia

Anticardiolipin antibodies (aCL) were evaluated in 65 consecutive patients with systemic lupus erythematosus using an enzyme linked immunoassay (ELISA) and were detected in 14 (22%). There was no association of aCL with active disease, specific clinical manifestations, high DNA binding or circulating immune complex levels. The presence of aCL was associated with lupus anticoagulant activity (p less than 0.001), positive VDRL (p less than 0.05), and lower mean platelet counts (p less than 0.05) and C3 levels (p less than 0.05). Both aCL and lupus anticoagulant activity were associated with positive Coombs' (p less than 0.01) and low C4 (p less than 0.01 and p less than 0.05, respectively). Analysis of red blood cell (RBC) eluates and absorption studies using fixed RBC suggested that some aCL may act as anti-RBC antibodies, likely directed at membrane phospholipid epitopes. Furthermore, we hypothesize that complement may participate as a cofactor maximizing lupus anticoagulant activity.     

Lupus Anticoagulants and Anticardiolipin Antibodies in Indian Women with Spontaneous,Recurrent Fetal Loss

Spontaneous and recurrent pregnancy loss are common complications of pregnancy resulting from varied causes including antiphospholipid syndrome (APS). Treatment of women with APS increases the chance of a subsequent successful pregnancy. The study aimed to find the prevalence of lupus anticoagulants (LA) and anticardiolipin antibodies (ACAs) in women with spontaneous/recurrent fetal loss and compare with women with normal obstetric history. Hundred women with spontaneous/recurrent fetal loss and 50 healthy pregnant controls were tested for LA by complete blood counts, Prothrombin time, Activated partial thromboplastin time (APTT), LA sensitive APTT and dilute Russell viper venom time (dRVVT) (screening and confirmatory) and ACAs (ELISA). LA was detected in 15 % patients using dRVVT confirmatory test and ACA in 5 %, all controls being negative. Twenty one % patients were detected by LA sensitive APTT (sensitivity 92.9 %, specificity 100 %) and 100 % with dRVVT screening test (sensitivity 98.8 %, specificity 100 %). We recommend that screening for antiphospholipid antibodies must be done in women with spontaneous/recurrent foetal loss even in the absence of other clinical manifestations using a combination of tests.     

Prevalence and isotype distribution of antiphospholipid antibodies in Chilean patients with systemic lupus erythematosus (SLE)

Previous studies have demonstrated that ethnicity plays a role in the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta2 glycoprotein I (abeta2-GPI) antibodies in systemic lupus erythematosus (SLE) patients. Few studies have been done in Latin American populations. Serum samples from 129 Chilean SLE patients were tested for IgG, IgM and IgA aCL and abeta2-GPI by ELISA. Clinical data were reviewed with the focus on clinical manifestations of antiphospholipid syndrome (APS). Positivity for at least one isotype of aCL was found in 30% of patients, while only 10% were positive for at least one isotype of abeta2-GPI. IgG was the most prevalent isotype for aCL (16%), and the isotype distribution was similar (4%) for abeta2-GPI. In general, the presence of aCL was significantly associated with the presence of abeta2-GPI, but a number of samples were positive for only one antibody, some of them associated with clinical manifestations of APS. ACL antibodies at medium-high titers were significantly correlated with thrombosis (P = 0.0007) and fetal loss (P = 0.009); however, the sensitivity of abeta2-GPI for detecting thrombosis and fetal loss was lower than aCL (19 and 17% vs 56 and 50%, respectively), and the specificity slightly higher (91 and 90% vs 84 and 82%). In Chilean SLE patients, aCL and abeta2-GPI antibodies are important in the evaluation of patients with APS. However, the utility of abeta2-GPI antibodies was limited by the low prevalence of these antibodies in comparison with other ethnic groups. Further studies are needed to define the basis of the observed differences among ethnic groups.     

Estimation of anticardiolipin antibodies, anti-beta2 glycoprotein I antibodies and lupus anticoagulant in a prospective longitudinal study of children with juvenile idiopathic arthritis

OBJECTIVE: Anticardiolipin antibodies (aCL) have been frequently detected in juvenile idiopathic arthritis (JIA), but have not been associated with disease activity or clinical features of the antiphospholipid syndrome (APS). Our aim was to determine aCL and anti-beta2 glycoprotein I (anti-beta2GPI) antibody levels and lupus anticoagulant (LA) in serial samples from children with JIA and to investigate the clinical significance of these antibodies. METHODS: The values of aCL, anti-beta2GPI and LA were prospectively followed in 28 children with JIA from disease onset. aCL and anti-beta2GPI were assayed by an ELISA method. Two monoclonal beta2GPI-dependent aCL (HCAL and EY2C9) were used as calibrators. LA was determined by a modified dilute Russell viper venom time test. RESULTS: Thirteen (46.4%) children with JIA were already positive for aCL at their first referral to our center. During the follow-up, the frequency of aCL decreased from 46.4% to 28.6%; however, it remained significantly higher compared with healthy children. In contrast, for anti-beta2GPI the difference in the frequency between the children with JIA and healthy children was not statistically significant. Serial determination of aPL levels in JIA patients revealed frequent fluctuations. Positive aCL persisted over time in 6 (21.4%) children with JIA, 6 (21.4%) children were initially positive for aCL, but became later negative, and 3 (10.7%) children were initially negative for aCL and became later positive. Persistently positive anti-beta2GPI were observed during the follow-up only in one patient, while none of the patients was persistently positive for LA. No association between aCL, anti-beta2GPI or LA and disease activity could be established. No patient with positive aCL, anti-beta2GPI or LA showed any clinical feature of APS. CONCLUSION: The discrepancy between the presence of aCL and anti-beta2GPI might indicate that the production of aCL in JIA is associated with an infectious trigger. Furthermore, the low frequency of anti-beta2GPI and LA could explain the limited prothrombotic potential of aPL observed in JIA. However, we found a distinct group of JIA patients with persistently positive aCL, the clinical implications of which are at the present time unknown.     

妊娠合并系统性红斑狼疮94例临床分析

目的 寻找妊娠合并系统性红斑狼疮(SLE)患者妊娠及产后不良母婴预后的因素.方法 回顾性分析北京协和医院妇产科收治的妊娠合并SLE患者的临床资料,根据SLE活动与否,将患者分为SLE不活动组和SLE活动组.用logistic回归分析影响不良母婴结局的危险因素.结果 妊娠合并SLE者97例,其中3例失访,94例SLE患者共96例次妊娠,96例次妊娠中SLE不活动组36例次,SLE活动组60例次.96例次妊娠中18例次为治疗性引产或人工流产,胎儿丢失7例次,活产71例次,3例新生儿死亡.SLE活动组早产、小于胎龄JD(SGA)、窒息发生率高于SLE不活动组(P＜0.05).logistic回归分析显示,胎儿不良结局与子痫前期/子痫、低血小板血症、SLE活动等因素有关(13值分别为2.463、2.228、2.769,P＜0.05).96例次妊娠中56例次孕前SLE稳定,其中22例次(39.3%)在妊娠期和产后发生SLE活动.共有24例子痫前期,2例子痫.合并狼疮肾炎(LN)者52例次,孕前LN控制稳定者有25例次(48.1%,25/52),其中稳定1年以上者22例次,妊娠期有12例次发生LN活动;而LN稳定短于1年者3例,妊娠期全部发生LN活动.4例产妇死亡,均发生于产后.logistic回归分析显示,子痫前期/子痫与LN活动呈正相关(β值2.658,P＜0.05),而SLE活动与孕前尿蛋白呈正相关(13值3.263,P＜0.05).结论 SLE患者妊娠后胎儿丢失、早产、SGA、新生儿窒息的发生率在SLE活动时显著增加.约1/3的SLE患者在妊娠后出现SLE活动,LN活动时子痫前期、子痫发生率显著升高.     

IgG and IgM anticardiolipin antibodies in patients with lupus with anticardiolipin antibody associated clinical syndromes

IgG and IgM anticardiolipin antibodies (aCL) were measured by a solid phase enzyme immunoassay in 64 patients with systemic lupus erythematosus who had one or more clinical disorders reported to be associated with aCL. We found the presence of IgG aCL was significantly associated with an increased incidence of cerebrovascular disease (p less than 0.01), a positive Venereal Disease Research Laboratories (VDRL) test (p less than 0.02) and prolonged partial thromboplastin time (PTT) (p less than 0.001). IgM aCL were associated with recurrent spontaneous abortion (p less than 0.05), thrombocytopenia (p less than 0.05) as well as a positive VDRL and prolonged PTT. The combination of high titer IgG and IgM aCL was associated with endocardial disease (p = 0.02), migraine (p less than 0.02), in addition to fetal loss (p less than 0.001).     

Clinical presentations and vascular histopathology in autopsied patients with systemic lupus erythematosus and anticardiolipin antibodies

OBJECTIVE: To examine histomorphological and immunohistological changes in an autopsy series of systemic lupus erythematosus (SLE) patients with or without anticardiolipin antibodies (aCL). METHODS: Fourteen SLE patients who died at our department from 1988 to 1996 were included. The patients' medical files were reviewed for the clinical history and the presence of IgG and IgM aCL. Autopsy samples of various organs, including regularly the kidneys, heart, brain and skin, were studied by standard histological methods and the direct immunofluorescence technique. RESULTS: Thirteen of 14 (93%) autopsied SLE patients were persistently positive for IgG aCL and had common overt thrombotic complications and/or other clinical features related to the antiphospholipid syndrome. Their autopsy tissue samples showed frequent occlusive vascular changes such as bland thromboses, thrombotic microangiopathy (TMA) related changes and arterial intimalfibrous hyperplasia. The immune complex related vascular changes were mostly unremarkable and present mainly in low aCL positive patients, who also had more aggressive types of lupus glomerulonephritis (GN). CONCLUSION: Increased IgG aCL were found in 13 out of 14 autopsied SLE patients who had predominant occlusive vascular histopathologic changes. The coincidence of bland thromboses with a characteristic TMA histopathology suggested two pathogenetic mechanisms associated with the presence of aCL, one related to abnormal coagulation and the other to endothelial cell injury. The extent of granular vascular immune deposits, typical of SLE, and the severity of lupus GN were inversely related to the aCL level.