Is the determination of anti‐beta2 glycoprotein I antibodies useful in patients with venous thromboembolism without the antiphospholipid syndrome?

Anti-beta2-glycoprotein I (beta2GPI) antibodies are frequently found in patients with lupus anticoagulant (LA). To investigate the prevalence of antibeta2GPI antibodies and their clinical impact in patients with a history of venous thromboembolism (VTE) without LA/anticardiolipin antibodies (ACA), we studied 503 patients [128 (36.2%) men, median age 41 years (interquartile range, IQR 28-54 years)] with previous thrombosis. A group of 113 individuals without VTE [43 (38.1%) men, age 46.7 years (IQR 38-52 years)] served as a control group. Among 418 patients without LA/ACA, anti-beta2GPI-IgG levels were elevated in seven (1.7%), -IgM in 15 (3.6%) and -IgA in 14 (3.3%) cases; in 58 patients with ACA, anti-beta2GPI-IgG levels were elevated in two (3.4%), six (10.3%) and three (5.2%), and in 27 with LA, they were elevated in 18 (66.7%), 19 (70.4%) and 10 (37%) respectively. Thus, the prevalence of elevated anti-beta2GPI antibodies was not increased in patients without LA/ACA but was strongly associated with LA. Patients without ACA/LA who had a recurrent event did not have higher prevalence of elevated anti-beta2GPI-IgG, -IgM or -IgA antibodies than those without a recurrent event. Thus, elevated antibeta2GPI antibodies are not likely to be a predictor of recurrent events in patients without LA. We conclude that determination of anti-beta2GPI antibodies does not improve the clinical management of patients with a history of VTE without LA/ACA.     

ANTIPHOSPHOLIPID ANTIBODIES IN PAEDIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS, JUVENILE CHRONIC ARTHRITIS AND OVERLAP SYNDROMES: SLE PATIENTS WITH BOTH LUPUS ANTICOAGULANT AND HIGH-TITRE ANTICARDIOLIPIN ANTIBODIES ARE AT RISK FOR CLINICAL MANIFESTATIONS RELATED TO THE ANTIPHOSPHOLIPID SYNDROME

Antiphospholipid antibodies (APA) are often associated withsevere clinical manifestations, especially in the setting ofsystemic lupus erythematosus (SLE). Here we have investigatedthe prevalence of anticardiolipin antibodies (aCL) and lupusanticoagulant (LA) in paediatric patients affected with SLE,JCA and overlap syndromes (OS) and correlated the presence ofaCL and LA with clinical features. aCL were assayed by enzyme-limitedimmunoassay; LA was determined by activated partial thromboplastintime and the kaolin clotting time test. aCL and LA assays wereperformed in parallel on at least two occasions over a 7–30-monthfollow-up. Fifteen out of nineteen (79%) SLE patients had aCLand 8/19 (42%) had LA. Six SLE patients displayed manifestationsthat were APA-related: deep venous thromboses, autoimmune haemolyticanaemia, pulmonary hypertension, neurological alterations. Fiveout of six symptomatic patients had both LA and high-titre aCL.In contrast, JCA and OS patients had usually low-titre aCL,no detectable LA and no APA-related manifestations. aCL persistedat high titre over time in SLE patients, but was only transientlydetected in JCA and OS patients. This study shows that the simultaneouspositivity for LA and high-titre aCL allows the identificationof paediatric SLE patients who are at risk not only for thrombosis,but also for other APA-related clinical features. KEY WORDS: Anticardiolipin antibodies, Lupus anticoagulant, Childhood systemic lupus erythematosus, Juvenile chronic arthritis, Overlap syndromes     

In vivo efficacy of intravenous gammaglobulins in patients with lupus anticoagulant is not mediated by an anti-idiotypic mechanism.

The authors have investigated the presence in commercially available intravenous gammaglobulins (IVIg) of anti-idiotypic antibodies directed to Lupus Anticoagulant (LA). In vitro incubation of 4 LA plasmas with increasing concentrations of IVIg (from 0 to 39 mg/ml) resulted in a dose-dependent inhibition of LA activity (the highest inhibitions ranged from 14.0 to 53.4%). Similar results were obtained when patients' plasma was substituted with total IgG (the highest inhibitions ranged from 43.0 to 55.0% and were obtained at IgG:IVIg molar ratios ranging from 1:15 to 1:50). Also the incubation of patients' F(ab')2 with F(ab')2 from IVIg produced a similar dose-dependent inhibition of LA activity. These data are suggestive of an in vitro idiotypic-anti-idiotypic interaction between LA and IVIg. However, when injected in patients with LA, IVIg do not seem to operate by this mechanism of action. In fact, reduction or disappearance of LA was only observed in 2 out of 4 patients; also the quick reappearance of LA activity was not consistent with the time course of anti-idiotypic response. Finally, this effect was reached by half the IVIg concentrations necessary to produce an appreciable inhibitory effect on LA activity in vitro. Thus, it is concluded that, even if IVIg contain anti-idiotypic antibodies reacting with LA, the clinical efficacy of IVIg treatment in patients with these autoantibodies should be attributed to other mechanisms.     

Anti-prothrombin antibodies combined with lupus anti-coagulant activity is an essential risk factor for venous thromboembolism in patients with systemic lupus erythematosus

Anti-prothrombin antibodies (anti-prothrombin) and anti-beta2-glycoprotein I antibodies (anti-beta2-GP I) are the most common and characterized anti-phospholipid antibodies (aPL) detected using specific enzyme-linked immunosorbent assay (ELISA) systems. Recently, lupus anti-coagulant (LA) activity detected by a phospholipid-dependent coagulation assay was reported to be associated with anti-prothrombin and/or anti-beta2-GP I. Here we show that the co-existence of IgG anti-prothrombin and LA activity might be an essential risk factor for venous thromboembolism (VTE) in patients with systemic lupus erythematosus (SLE). We examined not only the levels of antibodies to prothrombin and anti-beta2-GP I (both IgG and IgM isotypes) using an ELISA system, but also LA activity detected using both diluted Russell's viper venom time (dRVVT) and STACLOT LA test in 124 patients with SLE. The SLE patients were divided into four groups according to the results of ELISA and LA assay results for each aPL: group A, ELISA+ and LA+ group B, ELISA+ and LA-; group C, ELISA- and LA+ group D, ELISA- and LA-. Regarding IgG anti-prothrombin, the prevalence of VTE was significantly higher in group A (16/35 cases, 45.7%, P < 0.001, Fisher's exact probability test) than in the other groups (B, 2/30, 6.7%; C, 1/22, 4.5%; D, 1/37, 2.7%). With respect to IgM anti-prothrombin and IgG or IgM anti-beta2-GP I, the prevalence of VTE was higher in both groups A and C than in group D, but no statistical difference in prevalence was found between groups A and C. Multivariate logistic regression analysis of risk factors for VTE confirmed that the co-existence of IgG anti-prothrombin and LA activity was the only significant risk factor for VTE (odds ratio, 19.13; 95% confidence intervals, 4.74-77.18).     

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.     

The persistence of anticardiolipin antibodies is associated with an increased risk of the presence of lupus anticoagulant and anti-beta2-glycoprotein I antibodies

OBJECTIVE: We studied antiphospholipid antibodies (aPL) in blood samples from a cohort of individuals followed for thrombosis to determine whether the persistent presence of anticardiolipin antibodies (aCL) is associated with a greater likelihood of having lupus anticoagulant and/or anti-beta2-glycoprotein I antibodies (LA/abeta2GPI). METHODS: Blood samples from 353 individuals who had been tested for aCL on at least two occasions were tested for abeta2GPI and LA. Two groups were defined: aCL-persistent, who tested aCL-positive on at least two occasions, and aCL non-persistent, who tested aCL-positive on fewer than two occasions. Multivariate logistic regressions were performed using LA/abeta2GPI, LA and abeta2GPI as outcome variables and the percentage of aCL-positive tests as the predictor variable, adjusted for age, gender, family history of cardiovascular disease (CVD), systemic lupus erythematosus (SLE), smoking and number of venous (VT) and arterial thromboses (AT). RESULTS: Sixty-eight (19%) individuals were aCL persistent and 285 (81%) were aCL non-persistent. LA/abeta2GPI was found in 36 (53%) of the aCL persistent group and 38 (13%) of the aCL non-persistent group. The two groups were similar for age, gender and smoking. Family history of CVD, SLE, VT and AT were more frequent in the aCL persistent group. Multivariate analyses revealed that odds ratios for LA/abeta2GPI, LA and abeta2GPI were 1.34 [95% confidence interval (CI) = 1.22-1.47], 1.36 (95% CI = 1.24-1.50) and 1.47 (95% CI = 1.31-1.65) respectively for each 10% increase in aCL-positive tests vs 0% positive tests. CONCLUSION: Persistence of aCL positivity is associated with an increased risk of LA/abeta2GPI.     

Lupus anticoagulant and anticardiolipin antibodies in polytransfused beta thalassemia major

The currently used therapeutic strategies in beta thalassemia have prolonged the survival for many patients; this longer survival has been accompanied by the development of a number of unexpected complications, these include hemostatic derangements. The presence of anti-phospholipid antibodies (APA) (lupus anticoagulant, LA and anti-cardiolipid antibody, ACA) has recently been reported in polytransfused patients of beta thalassemia. In this study 50 patients with beta thalassemia major (beta-TM) who had received at least 20 transfusions were evaluated for presence of antiphospholipid antibodies and correlated with a number of clinical and hemostatic parameters. About 32% cases had developed a minor bleeding tendency and one also showed ecchymotic patch. None of the patients had thromboembolic episodes. LA was seen in 16% of cases. The mean age and number of transfusions were higher in LA positive patients as compared to LA negative patients however the results were not statistically significant. IgM ACA were detected in 6% of patients but no statistically significant correlation was found with age, number of transfusions, platelet count and coagulation parameters. IgG ACA were detected in 30% of cases and showed a significant correlation with number of blood transfusions (p = 0.016) and age (p = 0.031). Anti HCV antibodies were detected in 30% of patients out of which 1 had IgM ACA and 10 had IgG ACA. The latter showed a significant correlation with HCV infection. An increased incidence of LA and IgG ACA is found in polytransfused patients with beta-TM when compared to the normal healthy population but their clinical significance is yet not clearly understood.     

Relative value of different antiphospholipid antibodies detected in a department of internal medicine: retrospective study of 124 patients

PURPOSE: The value of antiphospholipid antibodies (aPL) detected in the sera of the patients of an Internal Medicine department is not univocal and is still much debated. To test the contribution of such new markers, we reviewed the records of patients having antiphospholipid antibodies detected between 1996 and 1997. METHODS: One hundred and twenty four patients, having at least one of these two aPL: lupus anticoagulant (LA), anticardiolipin antibodies (aCL), or one of these two anti-proteins: anti-beta 2glycoprotéin I antibodies (anti-beta 2GPI) or anti-prothrombin antibodies (aPT), were studied. LA was detected by a PTT-LA technique and aCL, anti-beta 2GPI and aPT by ELISA-sandwich techniques. For each patient we recorded sex, age, personal and familial history of thrombosis, fetal losses and systemic disease, the reason of aPL detection, the final diagnosis, activated partial thromboplastin time (aPTT), platelets count and type of aPL. RESULTS: The population was composed of 77 women (62%) and 47 men (38%) with a mean age of 54 years [12-92 years]. A thrombocytopenia was strongly correlated to aCL presence (OR = 6.15 et p = 0.03). The reason of aPL detection was venous thrombosis, recurrent fetal losses, systemic disease, infectious disease or fortuitous discovery of a prolonged aPTT. The final diagnosis was a systemic disease in 57% of cases, an infectious disease in 14.5%, a thrombosis in 4.5% and a neoplasia in 3%. LA was detected in 54% of patients, aCL in 39.5%, anti-beta 2GPI in 23% and aPT in 31%. No relationship between the aPTT value and the type of aPL could be established. CONCLUSION: Our study shows that familial histories of venous thrombosis or systemic disease are useful to enhance antiphospholipid antibodies detection; that LA is mostly associated to systemic and infectious diseases; that aCL and anti-beta 2GPI are predominant in case of venous thrombosis and that thrombocytopenia has to enhance aCL detection and the discussion about a possible APS.     

Acetylcholine receptor-specific suppressive T-cell factor from a retrovirally transformed T-cell line.

In both experimental and human myasthenia gravis an impairment in the immune regulation leads to an increased synthesis of antibodies against the nicotinic acetylcholine receptor (AcChoR). The present work reports the establishment of an AcChoR-specific suppressive T-cell line obtained by viral transformation of AcChoR-enriched murine T lymphocytes. Enriched T cells from Torpedo AcChoR-primed mice, prestimulated in vitro with antigen, were infected with radiation leukemia viruses and injected intravenously in congeneic recipient mice. Six months later lymphomas were observed in 20% of the injected mice and two of them, of donor origin, were established as permanent continuous cell lines in vitro. One of these lines, named LA41, expresses Thy-1.2, Lyt-2, and I-Jb surface markers. Culture supernatants of LA41 cells suppress the antigen-specific in vitro proliferation of Torpedo AcChoR-primed lymphocytes. This suppression is antigen-specific since the response induced by fetal calf AcChoR and by other antigens is not affected by addition of LA41 culture supernatant in the proliferative assay. LA41 culture supernatant injected in vivo at the time of antigen-priming suppresses also significantly the production of anti-AcChoR antibodies but not the synthesis of antibodies against other antigens--i.e., fetal calf AcChoR or alpha-bungarotoxin. These data show that LA41 cells constitutively produce Torpedo AcChoR-specific suppressor factor.     

Antiphospholipid antibodies and thrombosis in systemic lupus erythematosus: comparison of three lupus anticoagulant assays and anticardiolipin ELISA in 188 patients.

The presence of antiphospholipid antibodies (aPL) in 188 unselected patients with systemic lupus erythematosus was studied using the recalcification time, kaolin clotting time (KCT), dilute Russell's viper venom time (dRVVT) and anticardiolipin ELISA (aCL) to identify patients with a high or low risk of thrombosis among patients with aPL. aPL were detected by at least one method in 104 (55%) of the patients. Despite heterogeneity, lupus anticoagulant (LA) methods correlated reasonably well with each other (r = 0.736-0.968), but poorly with aCL (r = 0.241-0.549). Positivity in LA assays and immunoglobulin G (IgG)-aCL were associated with patients who experienced thrombosis (P less than 0.001 for all assays). Patients with both LA and aCL had experienced thrombosis more often than those having only one (odds = 6.3, P less than 0.001). When patients with aPL were ranked by relative strength of the finding and divided into tertiles, a history of thrombosis was associated with membership in the strongest tertile of at least one assay (odds = 4.2, P = 0.002). LA and aCL had similar sensitivities for thrombosis (61% and 63%, respectively), but LA was more specific than aCL (79% vs 53%). The best combination of two assays was KCT with dRVVT (61% sensitivity, 87% specificity). Maximal sensitivity (71%) for thrombosis could be achieved by adding IgG-aCL to these two assays, but specificity was lower (73%). In conclusion, a high thrombotic risk among patients with aPL was indicated by the simultaneous presence of both LA and aCL, strongly positive aPL, and, among aCL, IgG-class antibodies.     

Anticardiolipin antibodies and lupus anticoagulants comprise separate antibody subgroups with different phospholipid binding characteristics

Autoantibodies to phospholipid antigens can be characterized using solid phase immunoassays to detect anticardiolipin antibodies (ACA) or in phospholipid-dependent clotting tests where lupus anticoagulant (LA) activity can be demonstrated. It has not been established whether each activity is due to the same or separate antibody subgroups. Plasma from two patients with high levels of both activities were used for purification of ACA and LA using sequential ion-exchange, gel-filtration, and anti-Ig affinity chromatography. Plasma could be separated into fractions containing each activity in the absence of the other. In these fractions, antibodies responsible for LA activity do not bind to isolated phospholipids in solid phase immunoassays, and conversely antibodies binding in these assays (ACA) do not possess LA activity, suggesting LA are directed against a more complex lipid epitope. In addition, in one patient ACA was of IgG isotype only, whilst LA was due to IgG and IgM isotypes. In this patient, the IgG-ACA was heterogeneous with three peaks clearly separated on ion-exchange chromatography. Affinity purified antiphospholipid antibodies have been previously prepared from a number of patients using a phosphatidyl-serine column and antibodies purified in this manner possess ACA but not LA activity. Taken together, these data indicate that tests for ACA and LA define separable subgroups of phospholipid binding antibodies, thus explaining the discordance often seen between the two activities.     

Incidence of selected antiphospholipid antibodies in a group of patients with systemic lupus erythematosus

Antiphospholipid antibodies (APLA) present very heterogeneous groups of antibodies which can significantly and in various ways influence processes on different levels of coagulation cascade. Their presence can be accompanied with repetitive venous and arterial thromboses, recurrent loses of foetus, and thrombocytopenia. Incidence of these thrombotic disorders was monitored in a group of 46 patients with systemic lupus erythematodes (SLE). Positive lupus anticoagulant (LA), antiphospholipid antibodies complex, and thrombocyte counts were assessed. Thrombotic disorders were assessed in a retrospective analysis. In the LA+ group 62% of patients had history of venous thromboses, 31% had history of arterial thromboses, and 18% had history of spontaneous abortions. In a group without positive LA 18% of venous thromboses (p = 0.0006) and 6% of arterial thromboses (p = 0.03) were indicated. In the assessment of spontaneous abortions no statistically significant difference was found. An average value of thrombocytes in LA+ group was 152 +/- 66 x 10(5)/l, in LA- group 223 +/- 86 x 10(5)/l, which is statistically significant difference (p < 0.05). In the assessment of thrombotic disorders in a group with combination LA+ and APA+ statistical significance was indicated only in venous thromboses (p = 0.004). We can state from the results that in thrombotic disorders which can be seen in the framework of systemic tissue disorders positive LA and APA and a range of other factors such as activity of a basic disease, associated diseases, and treatment which can aggravate thrombotic disorders of individual patients can participate.     

Legionnaires' disease: antigenic peculiarities, strain differences, and antibiotic sensitivities of the agent.

Paired sera from victims of Legionnaires' disease showed, in many cases, significant rises in immunoglobulin G antibodies to both the causative agent (LA) of Legionnaires' disease and Chlamydia psittaci, but concurrent rises in immunoglobulin M antibodies only against LA. Guinea pigs experimentally infected with LA likewise responded with antibodies to both C. psittaci and LA. Guinea pigs infected with LA also reflected significant differences in antigenic makeup and in pathogenicity among four strains of LA examined. In antibiotic studies, rifampin was 200 times more effective than erythromycin and 17,000 times more effective than tetracycline in plaque reduction tests of LA in monolayer cultures of primary chick embryo cells. An isolate of LA recovered from a healthy person was compared with three isolates from persons with fatal infections.     

An ELISA system to detect anti-factor VIII antibodies without interference by lupus anticoagulants. Preliminary data in hemophilia A patients

BACKGROUND AND OBJECTIVES. Difficulties in identifying the coexistence of neutralizing anti-factor VIII antibodies (anti-fVIII) and lupus anticoagulant (LA) are mainly due to the interference of LA on anti-fVIII assays. Our aim was to reveal the presence of anti-fVIII using a system that is not affected by LA. DESIGN AND METHODS. We developed an enzyme-linked immunosorbent assay (ELISA) method that uses phospholipid-free recombinant factor VIII as the antigen. A monoclonal anti-fVIII was tested as a positive control, excluding non-specific binding by using two unrelated monoclonal antibodies. The ELISA was performed on hemophilic plasmas with anti-fVIII and negative LA (n=12) or without inhibitors (n=12). Two hemophilic plasmas with LA and presumably anti-fVIII were also assayed. Positive LA (n=12) and normal (n=10) plasmas were tested as negative controls. RESULTS. All (12/12) plasmas with anti-fVIII and 5/12 hemophilic plasmas without inhibitors were positive; LA and normal plasma controls were negative. INTERPRETATION AND CONCLUSIONS. Results presented here show that LA does not interfere with the anti-fVIII ELISA. However, the assay detects both neutralizing and non-neutralizing anti-fVIII antibodies, therefore a neutralizing effect must be confirmed through functional tests.     

In ECAT veritas?

The laboratory criteria of the antiphospholipid syndrome include one coagulation assay (lupus anticoagulant [LA]) and two solid phase assays (anticardiolipin [aCL] and anti-?(2)glycoprotein I antibodies [a?(2)GPI]). External quality control (EQC) surveys show that negative and clearly positive LA samples are classified correctly by about 95% of laboratories. For 'weak' LA there is a wide variability in samples' classification. Furthermore, when a weak LA sample is used in two different EQC surveys more than 50% of laboratories classify it differently. In some surveys weak LA samples were found to be positive for aCL and for a?(2)GPI by a majority of laboratories; the main reason for laboratories which classified these samples as LA negative was a negative result in the mixing test. It is likely that, depending on the sensitivity of the assay, a weak LA cannot be detected anymore after 1:1 dilution of the sample with normal plasma. Therefore, we recommend the use of integrated assays, such as screen/confirm ratios, for the detection of weak LA samples.     

Detection of lupus anticoagulant identifies patients with autoimmune haemolytic anaemia at increased risk for venous thromboembolism

Venous thromboembolism (VTE) is a well-recognized complication of autoimmune haemolytic anaemia (AIHA), and is a major cause of morbidity and mortality in this disorder. However, the incidence, pathogenesis and risk-factors for VTE in AIHA remain poorly defined. Lupus anticoagulants (LA) and anticardiolipin (ACA) antibodies are autoantibodies directed against epitopes on prothrombin or beta2 glycoprotein I (beta2-GPI). Both LA and ACA (together called antiphospholipid antibodies, APLA) are associated with VTE. We have prospectively studied the occurrence of VTE and APLA in 30 patients with AIHA. VTE was objectively documented in eight (27%) patients. APLA were detected in 19 (63%) patients with AIHA, of whom nine (30%) had a LA and 17 (57%) ACA. Seven patients had both LA and ACA. Among the eight patients with VTE, LA was detected in five (63%) and ACA in four (50%). There was a statistically significant association between presence of LA and occurrence of VTE (RR: 7.50, 95% CI: 1.25-45.2, P = 0.03). VTE is a frequent and life-threatening complication of AIHA. Detection of the lupus anticoagulant in patients with AIHA identifies individuals at significantly increased risk for VTE. Future studies should address the role of prophylactic anticoagulation in patients with AIHA.     

Antiphospholipid Antibodies in a Heterogeneous Group of Patients: Experience from a Central Laboratory

The aim of this study was to evaluate the prevalence and the performance of lupus anticoagulant (LA) tests in a heterogeneous group of patients and to investigate the sociodemographic characteristics, patterns of referral, clinical manifestations and outcomes among these patients. The medical charts of 725 patients referred to a central coagulation laboratory during a 12-month period for LA were reviewed. The data collected included demographic characteristics, the specialty of the referring physicians, the clinical indications for ordering the test, and the influence of the test results on the diagnosis and the treatment approach. Special attention was paid to identifying clinical manifestations known to be associated with antiphospholipid antibodies (APLA). A positive test was defined by abnormal results obtained by at least two techniques from the reagents used and confirmed by a platelet-neutralising procedure. χ² and t-tests were used for independent samples. Fifty-six patients (7.7%) were found to have LA. Rheumatologists and gynaecologists emerged as the major contributors to this group. The presence of LA was significantly associated only with systemic lupus erythematosus and thrombocytopenia. The number of patients treated with antiaggregants or anticoagulants tripled following the test results. A positive dRVVT test strongly correlated with elevated anticardiolipin antibodies. We concluded that LA tests are ordered by a variety of physicians but yield better results when ordered by rheumatologists and gynaecologists. In this heterogeneous cohort, it was most useful in the investigation of thrombocytopenia and suggests a pathogenetic role in this condition. The dRVVT test correlates most closely with elevated anticardiolipin antibodies. Received: 10 December 2001 / Accepted: 27 May 2002     

Antiphospholipid antibodies in primary Sjögren's syndrome: prevalence and clinical significance in a series of 74 patients

The aim of this study is to determine prevalence, clinical significance of antiphospholipid antibodies (aPL) including anticardiolipin antibodies (aCL), anti-beta2GP1 and lupus anticoagulant (LA) in a cohort of 74 patients with primary Sj?gren's syndrome (pSS) according to revised European criteria. aPL were found in 25 (34%) patients; IgG in 23 (12 had low titres, six moderate titres and five high titres) and IgM in five (three and two had respectively moderate and high titres). Eight (11%) patients were found to have LA; anti-beta2GP1 antibodies were detected only in three (4%) patients. Only two patients with LA, aPL and beta2GP1 had recurrent venous thrombosis. One patient with moderate titres of aPL exhibited recurrent spontaneous foetal losses. Peripheral neuropathies without cryoglobulinemia were more frequent in the aPL group. Other systemic involvements of pSS were the same in both groups with or without aPL. Patients with aPL have more concurrent immunological diseases such as thyroiditis and primary biliary cirrhosis and a higher prevalence of hypergammaglobulinemia (P < 0.05). Even if aPL prevalence reached 30% in pSS, titres were usually low, with a close correlation with hypergammaglobulinemia but not with antiphospholipid syndrome, which is related to positivity of both LA and aPL.     

Specificities of platelet autoantibodies and platelet activation in lupus anticoagulant patients: a relation to their history of thromboembolic disease

Lupus anticoagulants (LA) prolong in vitro phospholipid-dependent coagulation tests, but are associated with thromboembolic disease (TE). However, a subgroup of individuals with LA has no TE, and it is therefore desirable to distinguish those at risk for TE from those without. Whether platelets have a primary role in the development of TE is not clear yet. We determined platelet autoantibodies to identify a specific platelet target which is associated with platelet activation in 97 patients with a long history of detectable LA, 65 patients with TE (LA/TE+), and 32 individuals without TE (LA/TE-). Thrombocytopenia was more common in the LA/TE- than in the LA/TE+ group (P < 0.05). Both groups had platelet antibodies, but the frequency of antibodies was lower in LA/TE+ than LA/TE- patients (P < 0.01), who had higher antibody titres against glycoprotein IIb/IIIa and glycoprotein Ib/IX (P < 0.05). Also, their platelets were more activated, as determined by PAC-1 binding (P < 0.01). These differences were also noted if patients with arterial thrombosis were evaluated separately. These findings in LA/TE- individuals were similar to those in patients with chronic autoimmune thrombocytopenia. However, there was no autoantibody target identifiable to distinguish between LA/TE- from LA-TE+ individuals. We therefore conclude that the presence of platelet antibodies, even if associated with platelet activation, is not sufficient to dispose LA patients to thromboembolic disease.     

Do antibodies to beta2-glycoprotein 1 contribute to the better characterization of the antiphospholipid syndrome?

The aim of this study was to determine if the measurement of anti-beta2-glycoprotein I antibodies (abeta2-GPI) in serum levels contributes to the better characterization of the clinical situation of patients with antiphospholipid syndrome (APS). For this purpose abeta2-GPI of both isotypes was measured in 42 patients with APS and 32 SLE patients without APS. Clinical records of all patients were thoroughly reviewed. The presence of abeta2-GPI was correlated with the clinical manifestations of APS and compared with the presence of anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) activity. There was a positive correlation between levels of aCL and abeta2-GPI for both IgG and IgM isotypes (rho of Spearman=0.82 and 0. 64 respectively, P=0.0001). Both antibodies presented significantly higher titres in LA positive patients (P<0.05). The specificity for APS was 91% for IgG abeta2-GPI vs 75% for IgG aCL and 87% for IgM abeta2-GPI vs 81% for IgM aCL. 68% of patients with thrombosis of 100% of patients with thrombocytopenia showed positive tests for all three markers (aCL, LA, abeta2-GPI). Simultaneous presence of circulating LA and high titres of both aCL and abeta2-GPI identify a subset of patients with primary APS (PAPS) who have a more severe clinical course of the disease. Although the specificity of abeta2-GPI IgG is higher than that of aCL IgG, when all three tests are performed abeta2-GPI testing provides only additional information to that of aCL and LA. Therefore, we concluded that the abeta2-GPI test should not be considered as a substitute for conventional LA or aCL assays. However, performance of abeta2-GPI seems to be important in PAPS with high aCL titres, to alert the physician about the risk for the worst course of the illness.