Avidity of anti-ß2-glycoprotein I antibodies in patients with antiphospholipid syndrome.

Antibodies against ß(2)-glycoprotein I (anti-ß(2)GPI) are one of the hallmarks of the antiphospholipid syndrome (APS). However, they are heterogenic regarding their epitope specificity, pathogenic mechanisms and their avidity. In the current study we present some outstanding issues about avidity of anti-ß(2)GPI antibodies. Our results confirmed that high avidity anti-ß(2)GPI are associated with thrombosis and APS, while in low avidity anti-ß(2)GPI group non-APS (predominantly systemic lupus erythematosus) patients prevailed.

The avidity of anti-beta2-glycoprotein I antibodies in patients with or without antiphospholipid syndrome: a collaborative study in the frame of the European forum on antiphospholipid antibodies.

OBJECTIVE: The objective of this study was to extend the findings of the preliminary study by measuring the avidity of IgG anti-ß2-glycoprotein I antibodies (anti-ß2-GPI) on a larger group of patients with primary or secondary antiphospholipid syndrome (APS) and anti-ß2-GPI positive patients without APS in the frame of the European Forum on antiphospholipid antibodies (aPL). METHODS: Serum from 137 patients with primary APS, APS associated with autoimmune diseases, and patients with autoimmune diseases other than APS from five EU rheumatology centres were tested for anti-ß2-GPI antibodies. The 109 patients who were sera positive for anti-ß2-GPI by the in-house anti-ß2-GPI enzyme-linked immunosorbent assay (ELISA) at the Immunology Laboratory, UMC Ljubljana were selected for further testing on avidity with chaotropic anti-ß2-GPI ELISA. RESULTS: High, low and heterogeneous avidity IgG anti-ß2-GPI was found in 32/109, 17/109 and 60/109 patients respectively. Significantly more patients with APS were in the high avidity than in the low avidity anti-ß2-GPI group, while the opposite was observed for non-APS (both p < 0.001). The most common clinical feature among patients with high avidity anti-ß2-GPI was thrombosis, mainly due to venous thrombosis (p < 0.01 and p < 0.001, versus low avidity anti-ß2-GPI group). CONCLUSION: Patients with or without APS had anti-ß2-GPI of high, low or heterogeneous avidity. High avidity anti-ß2-GPI was associated with thrombosis and APS, while in the low avidity anti-ß2-GPI group non-APS (predominantly SLE) patients prevailed. Determination of anti-ß2-GPI avidity should be considered in the analytical strategies for further differentiation of patients with anti-ß2-GPI antibodies.

Prolactin's role in the pathogenesis of the antiphospholipid syndrome.

Increased levels of serum prolactin have been reported in patients with various autoimmune diseases and have been associated with lupus disease activity. Currently, there is a lack of data regarding hyperprolactinaemia in patients with the antiphospholipid syndrome. Hence, this study was carried out in order to evaluate the prevalence and clinical significance of hyperprolactinaemia in antiphospholipid syndrome. A total of 172 European patients with antiphospholipid syndrome and 100 geographically and sex-matched healthy controls were included in the study; none had obvious causes of hyperprolactinaemia. All patients underwent clinical assessment for disease manifestations, in addition to laboratory assessment for serum prolactin, antiphospholipid antibodies and some other biomarkers of autoimmune diseases. The tests were performed utilizing the LIAISON® Analyzer (DiaSorin, Sallugia Italy). Hyperprolactinaemia was detected in 21/172 patients with antiphospholipid syndrome and 0/100 controls (p < 0.001). This significant difference was present in both genders and was obvious even after subgrouping the patients into primary and secondary antiphospholipid syndrome. When clinical features were compared, hyperprolactinaemia was associated with reproductive failure, including early and late pregnancy loss (p < 0.05), as well as intrauterine growth retardation (p < 0.05). Hyperprolactinaemia was negatively related to arthralgias, venous thrombosis, pulmonary microthrombosis, pulmonary hypertension in both primary antiphospholipid syndrome and antiphospholipid syndrome secondary to other diseases, and to neurological manifestations in primary antiphospholipid syndrome (p<0.05). The data indirectly imply that prolactin may play a role in the pathogenesis of antiphospholipid syndrome, especially antiphospholipid syndrome-related reproductive failure.

Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus.

An inception cohort of patients with systemic lupus erythematosus from 14 European centres was followed for up to 5 years in order to describe the current early disease course. At inclusion patients (n = 200, 89% female, mean age 35 years, 97% Caucasian, mean SLEDAI 12.2) fulfilled a mean of 6.5 ACR classification criteria. The most prevalent criteria were antinuclear Ab presence (97%) followed by anti-dsDNA Ab (74%), arthritis (69%), leukocytopenia (54%) and malar rash (53%), antiphospholipid Ab (48%) and anti-synovial membrane Ab (21.6%). Clinical signs of lupus nephritis (LN) were present in 39% with biopsy-confirmed LN seen in 25%. Frequent additional findings were hypocomplementaemia (54%), anti-SSA Ab (49%), alopecia (26%) and Raynaud's phenomenon (31%). There were few regional differences in disease presentation and management. One and 5-year survival rates were 99% and 97% respectively. During the mean follow-up of 4.1 years 25% entered a state of early disease quiescence by global physician assessment, but the overall risk of subsequent flare was 60%. Maximum SLEDAI scores decreased over time, but 45% of patients accrued damage (SDI >or=1) for which baseline presence of proteinuria and persistent disease activity were independent predictors. The results indicate minor differences in SLE presentation and treatment within various regions of Europe and a high diagnostic reliance on anti-dsDNA Ab. Despite early reductions in disease activity and improved mortality, the risk for disease flare and damage development is, however, still substantial, especially in patients not entering an early remission.

Common infectious agents prevalence in antiphospholipid syndrome.

Antiphospholipid syndrome is characterized by thrombosis and pregnancy loss. Infections are generally associated with autoimmune diseases, but in the setting of antiphospholipid syndrome this link has been suggested as having a pathogenic role. In this study, 98 patients with antiphospholipid syndrome were screened for antibodies directed to several infectious agents. The main finding in this study is the significantly higher prevalence of IgM antibodies to toxoplasma and rubella. This novel finding suggests that these infections might be associated with antiphospholipid syndrome. As autoimmune diseases and, in particular, antiphospholipid syndrome are associated with infections, mainly the catastrophic type of the syndrome, this finding implies that a current infection with these agents, i.e. toxoplasma and rubella, might either be related to the pathogenesis of antiphospholipid syndrome or alternatively to its manifestations.

Genetic polymorphisms of glutathione S-transferases and disease activity of rheumatoid arthritis.

OBJECTIVES: Glutathione S-transferases (GST); GST-mu1 (GSTM1), GST-pi1 (GSTP1) and GST-theta1 (GSTT1) have peroxidase activity towards cytotoxic metabolites produced in inflammatory reactions, the main feature of rheumatoid arthritis (RA). Genetic polymorphisms in GSTM1, GSTP1 and GSTT1 modify the enzyme conjugation capacity and may be associated with the activity of RA. METHODS: A genotyping approach was used to analyze GSTM1-0, GSTT1-0 and GSTP1 Ile105Val and Ala114Val polymorphisms in 213 RA patients. Disease activity was assessed by the disease activity score of 28 joint counts (DAS28) twice for each patient and mean DAS28 values were calculated. RESULTS: The patients with GSTT1-0 genotype had a higher risk for developing high activity RA than the patients with GSTT1 genes present (p=0.028, OR=2.761, 95% CI=1.114-6.843). An interaction between the GSTT1 polymorphism and smoking was observed. In the group of smokers, the carriers of a homozygous deletion GSTT1 had an 8.5-fold higher risk for developing high disease activity than the patients with the GSTT1-1 genotype (p=0.004, OR=8.640, 95% CI=1.995-37.426). GSTM1 and GSTP1 polymorphisms were not associated with the disease activity. CONCLUSION: Our results suggest that the presence of the GSTT1-0 genotype contributed to higher disease activity in RA patients. The risk for developing highly active RA was the highest in smokers with the GSTT1-0 genotype.

Autoimmune and proinflammatory activity of oxidized immunoglobulins.

AIMS: Oxidation reactions can modify protein activity or specificity. Recently, a novel redox-reactive family of autoantibodies was described, which indicated involvement of altered antibodies (beside altered antigens) into autoimmune reactions. The aim of our study was to determine the binding capacity alterations of electro-oxidized blood donors' IgGs, and to evaluate their effects on released proinflammatory interleukin 6 in HUVEC. RESULTS: We found out that 1.) Isolated blood donor IgGs bound after electro-oxidation to beta2-glycoprotein I, cardiolipin, citrullinated cyclic peptide and protein 3 by enzyme-linked immunosorbent assay, extractable nuclear antigens by counterimmuno-electrophoresis, and cell antigens by indirect immunofluorescence; 2.) Alterations in immunoreactivity of IgGs due to oxidation highly depend on electric current, time of exposure and the presence of antioxidants, 3.) Treatment of HUVEC with oxidized IgGs resulted in changed cell morphology, accompanied by an increase in released interleukin-6. CONCLUSIONS: Our data suggest repeatable transformation of antibodies present in the blood of healthy persons and patients. Inter-individual differences in chemical stability of antibodies, patient's antioxidant status, and the microenvironmental changes at the cellular level may influence the range of antibody alterations and their involvement in pathophysiological autoimmune processes.

Prevalence and clinical associations of anti-Ku antibodies in patients with systemic sclerosis: a European EUSTAR-initiated multi-centre case-control study.

OBJECTIVES: To determine the prevalence of anti-Ku antibodies in 625 patients with systemic sclerosis (SSc) from six European rheumatological centres and to evaluate their clinical and serological characteristics. METHODS: Sera of 625 consecutive patients with either limited cutaneous or diffuse cutaneous SSc were tested for antibodies to Ku antigen together with other extractable nuclear antigens by counterimmunoelectrophoresis. A case-control design with calculation of bootstrap 95% confidence intervals derived from anti-Ku negative control patients was used to evaluate clinical associations of anti-Ku antibodies. Sera from anti-Ku positive patients with SSc and a control group were additionally tested by immunofluorescence on Hep-2 cell substrates and line immunoassay. RESULTS: Anti-Ku antibodies were found in the sera of 14/625 (2.2%) patients with SSc. Of 14 anti-Ku positive patients with SSc, 10 had no other anti-extractable nuclear antigen (ENA) antibodies detected by counterimmunoelectrophoresis. Using a case-control study design, anti-Ku antibodies were significantly associated with musculoskeletal manifestations such as clinical markers of myositis, arthritis and joint contractures. In addition, a significant negative correlation of anti-Ku antibodies was found with vascular manifestation such as fingertip ulcers and teleangiectasias. There was a striking absence of anti-centromere antibodies as well as anti- polymyositis (PM)/scleroderma (Scl) antibodies in patients that were anti-Ku positive. As expected, anti-Scl70 and punctate nucleolar immunofluorescence patterns were present only in single cases. CONCLUSION: This is the largest cohort to date focusing on the prevalence of anti-Ku antibodies in patients with SSc. The case-control approach was able to demonstrate a clinically distinct subset of anti-Ku positive patients with SSc with only relative clinical differences in skeletal features. However, the notable exceptions were signs of myositis. This shows the importance of anti-Ku antibody detection for the prediction of this specific clinical subset.

Acinar epithelial cell laminin-receptors in labial salivary glands in Sjögren's syndrome.

OBJECTIVE: To analyze the epithelial cell-basement membrane attachment, in particular in the secretory end pieces (responsible for secretion of saliva) and in Sjögren's syndrome (SS) characterized by acinar cell failure. METHOD: Immunohistochemistry with laminin receptor chain-specific monoclonal antibodies to integrin (Int) subunits, Lutheran blood group antigen and alpha-dystroglycan. RESULTS: Only acinar cells contained Int alpha1 and alpha2 subunits. This staining was interrupted but strong in controls, but very weak in SS. Both acinar and ductal cells contained Int alpha3, alpha6, b1 and b4 and Lutheran blood group antigen and ductal cells also contained alpha-dystroglycan. These staining patterns were similar in SS and controls. CONCLUSIONS: Binding of the acinar and ductal cells to the basement membrane laminins seems to be mediated by Int alpha3b1, alpha6b1 and alpha6b4 integrin-receptors and Lutheran blood group antigen and alpha-dystroglycan non-integrin receptors. This structure-supporting system is intact in SS, compatible with the maintenance of the tubuloalveolar architecture of the SS glands. The irregular staining pattern of the acinus-specific Int alpha1b1 and alpha2b1 was compatible with a regulated signaling role, which was apparently impaired in SS. Indeed, their laminin counterparts (Lm -1/111 and -2/211) are also aberrant in SS revealing this as the central cell-matrix defect in the syndrome.

Beta2-glycoprotein I and its clinical significance: from gene sequence to protein levels.

In order to elucidate beta2-GPI at the DNA level and characterize its polymorphisms, mRNA expression, protein levels and clinical significance at each of these steps, a molecular review of beta2-GPI literature was performed. The human beta2-GPI complete nucleotide sequence has been reported and it consists of 8 exons separated by large introns. The beta2-GPI gene is polymorphic with four alleles. The distribution of point mutations can be significantly different between various racial populations. DNA variation studies of the beta2-GPI gene identified a total of 151 single-nucleotide polymorphisms, 26 of which are within regions with potential clinical significance. Southern blot analysis indicated the presence of one gene product only. An atypical TATA box and a hepatic nuclear factor-1 element are both essential for beta2-GPI promoter activity. Transcription factor binding sites for STAT, CREB, C/EBPbeta, NF-1, AP-1, NFAT, HNF-3beta and HNF-1 have been identified in the promoter region of the beta2-GPI gene by computer analysis. The beta2-GPI transcriptional signal of 1.5 kb was detected in Northern blot analysis and its 326-amino-acid sequence was found to be one of the most proline-rich eukaryotic proteins. Amino acid substitutions have been shown to be associated with loss of phospholipid binding, development and recognition of antiphospholipid antibodies.

Changes in avidity and specificity of IgG during electro-oxidation. Relevance of binding of antibodies to beta2-GPI.

The immune response may be changed due to altered proteins or modifications of immunoglobulins, including oxidative processes. The susceptibility to oxidative modifications depends greatly on amino-acid moiety composition due to chemical characteristics (instability) of their side-chains. Initial steps of oxidation may change the specificity and avidity of immunoglobulins due to chemical alteration of the hypervariable region. The oxidation of antibodies increases the hydrophilic nature of the paratopes and makes them more susceptible for the binding to cationic surfaces even without the strong surface-to-surface fitting. The electro-oxidation of IgG significantly changes the immunoreactivity and specificity of IgG fractions, regardless of the initial immunoreactivity to a specific autoantigen also in healthy persons. Data are presented on changes in the immunoreactivity as well as the avidity of antibodies against beta2-glycoprotein I after being exposed to direct current. ELISA measurements showed increased reactivity of anti-beta2-glycoprotein I antibodies at the beginning and various, fluctuating results after prolonged exposure to electro-oxidation. Inter-individual differences in chemical stability of immunoglobulins and patient's antioxidative status may influence the range of their alterations and their impact on health/disease balance.

Serum amyloid A in autoimmune thrombosis.

The objectives of this study were (1) to determine how levels of serum amyloid A (SAA), high sensitivity C-reactive protein (CRP) and interleukin-6 (IL-6) correlate to autoimmune diseases in patients with or without thrombosis, and (2) to discuss the parameters that influence the relative SAA values. SAA, CRP and IL-6 concentrations were determined by enzyme linked immunosorbent assay (ELISA). 84 patients with secondary antiphospholipid syndrome (SAPS), primary antiphospholipid syndrome (PAPS), systemic lupus erythematosus with antiphospholipid antibodies (SLE+aPL), SLE, venous thrombosis (VT), arterial thrombosis (AT) were compared to healthy donors (n=60). The percentages of patients above cut-off were highest in the SAPS, SLE and SLE+aPL groups. Significant differences were observed between healthy donors and inflammatory groups of patients (SAPS and SLE+aPL) in all three measured parameters. SAA and CRP were shown to be correlated to a greater extent in SAPS patients than SLE+aPL patients. In summary, this cross-sectional, retrospective, small study and accompanying clinical considerations limit the ability to make definite conclusions. SAA would not serve as a useful marker for venous, arterial thrombosis or PAPS (pro-coagulant events). It could however, be a good predictor of progression from a non-inflammatory thrombotic condition to an inflammatory one.

Avidity of anti-beta-2-glycoprotein I antibodies.

The terms affinity and avidity are often used indiscriminately, despite clearly differing. Since affinity refers to monovalent binding of antibodies to a monovalent epitope, the majority of data on the binding of anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) characterized their avidity rather than affinity. Anti-beta2-GPI were generally believed to be of low avidity, but heterogeneous avidity of patients' IgG anti-beta2-GPI has been demonstrated. High avidity anti-beta2-GPI monoclonals were reported to possess higher pathogenicity than low avidity anti-beta2-GPI. Polyclonal high avidity anti-beta2-GPI were found to be more common in patients with antiphospholipid syndrome (APS) and associated with thrombosis. Some conformational changes of beta2-GPI are required for the binding of polyclonal anti-beta2-GPI to the antigen: neither high density of the antigen nor high avidity of the anti-beta2-GPI alone is sufficient for the recognition. Avidity of anti-beta2-GPI should be considered in any attempt of inter-laboratory standardisation and/or evaluation of anti-beta2-GPI enzyme-linked immunosorbent assay (ELISA).

Avidity of anti-beta2-glycoprotein I and thrombosis or pregnancy loss in patients with antiphospholipid syndrome.

We aimed to evaluate avidity of anti-beta(2)-glycoprotein I antibodies (anti-beta(2)-GPIs) in patients with antiphospholipid syndrome (APS) at the time of acute thrombotic events or pregnancy loss as compared with clinical event-free periods. To do so, 69 sera samples from 16 patients (6 with primary APS and 10 with APS secondary to systemic lupus erythematosus ) were selected on the basis of anti-beta(2)-GPI positivity. Avidity of IgG anti-beta(2)-GPIs was determined by chaotropic enzyme-linked immunosorbent assay (ELISA), using increased NaCl concentration during antibody binding. High, heterogeneous, and low-avidity anti-beta(2)-GPIs were measured in APS patients, with no clear pattern regarding the time of thrombotic events or pregnancy failure. In general, anti-beta(2)-GPI avidity did not change substantially during disease course. We concluded that avidity of anti-beta(2)-GPIs appears to be a rather stable parameter in an individual APS patient. Considering the previously shown association of high-avidity anti-beta(2)-GPIs with venous thrombosis, avidity of anti-beta(2)-GPIs may be a better predictor of predisposition to thrombosis and unsuccessful pregnancy than levels of antiphospholipid antibodies, which may fluctuate over time owing to several factors.

Human leucocyte urokinase inhibitor--purification, characterization and comparative studies against different plasminogen activators.

A plasminogen activator inhibitor (PA-I) which inhibits primarily plasminogen activator of the urokinase type (u-PA) was isolated from the cytosol of human peripheral leukocytes. The inhibitor was isolated using ion exchange chromatography, gel filtration and FPLC. This inhibitor has an apparent molecular weight of 45 kDa, determined by SDS-PAGE, and a pI of 5.5-5.7. The inhibitor is a fast reacting inhibitor, is thermally unstable and is inactivated outside the pH range 7-9. Treatment of cytosol to pH 9 for 30 min at 37 degrees C resulted in a large increase in inhibitory activity. Antibodies against human placental UK-I completely quenched the inhibitory activity of human leucocyte UK-I.

Panconductional defect in mixed connective tissue disease: association with Sjogren's syndrome.

A patient in whom mixed connective tissue disease in association of Sjögren's syndrome had previously been diagnosed, experienced a syncopal attack. Electrocardiographic monitoring revealed periods of profound sinus bradycardia, sinus arrest with slow junctional escape rhythm, and first degree atrioventricular block during several episodes of dizziness. Complete right bundle branch block was a constant finding in this patient. Sinoatrial conduction time and sinus node recovery time were prolonged. Coronary heart disease was excluded by normal coronary arteriographic findings. This patient represents a rare case of cardiac involvement in mixed connective tissue disease.

Prevalence of antiphospholipid antibodies in deep vein thrombosis and their relationship to blood coagulation and fibrinolysis.

Elevated levels of antiphospholipid antibodies are associated with an increased risk of thrombosis. To establish the prevalence of these antibodies in deep vein thrombosis (DVT), IgG and IgM antibodies to cardiolipin (aCL) and phosphatidylserine (aPS) were determined by enzyme-linked immunosorbent assay in 118 patients with DVT either during an acute episode (N = 53) or at least 2 months after acute DVT (N = 65). Most patients (76%) had proximal leg DVT and no one had evident autoimmune disorder. aCL and aPS values higher than 4 standard deviations above the mean value of the control group (147 blood donors) were considered increased. Increased IgG aCL were observed in 10% of DVT patients (controls: 5%, not significant), increased IgG aPS in 16% of DVT patients (controls: 5%, p less than 0.005) and both types in 4% of DVT patients (controls: 3%, not significant). In the subgroup of 41 patients with previous idiopathic DVT, prevalence of increased IgG aPS was the highest: 27% (p less than 0.001). Increased antibodies of IgM isotype were observed in 3% (aCL) and 2% (aPS) of all DVT patients (controls: 8% and 4%, respectively, not significant). Elevated IgG aCL or aPS were not associated with significant changes in platelet count, antithrombin III and protein C. However, in patients with increased IgG aPS deficient fibrinolysis due to high plasminogen activator inhibitor activity was observed before and after 20 min upper arm venous occlusion. DVT patients with increased IgG aPS might be exposed to a greater risk of rethrombosis due to deficient fibrinolysis than DVT patients without these antibodies.

Fluctuation of anti-Ro/SS-A antibody levels in patients with systemic lupus erythematosus and Sjögren's syndrome: a prospective study.

OBJECTIVE: To determine whether the titers of anti-Ro/SS-A (Ro) antibodies fluctuate during the course of SLE and Sjögren's syndrome (SS) in parallel with disease activity, and if such fluctuations could be used to predict disease flares. We also evaluated whether the anti-Ro profile (anti-Ro 52, anti-Ro 60) changes over time, since such information could provide new insights into the induction and regulation of anti-Ro autoimmunity. METHODS: Sixteen patients with SLE and 15 patients with SS, all anti-Ro/SS-A antibody positive, were followed up for two years at three-month intervals. Clinical and laboratory parameters of disease activity were examined. Determination of the anti-Ro/SS-A titer was performed by counterimmunoelectrophoresis and the fine anti-Ro antibody specificity was determined by immunoblotting. RESULTS: The titers of anti-Ro antibodies fluctuated during the course of the illness in both SLE and SS patients. In SLE patients these changes were not (except in one case) associated with disease activity nor were they predictive of disease flares. The same was true for the SS patients, with the exception of two patients with skin vasculitis in whom anti-Ro antibody titers fluctuated in parallel with the disease activity. The anti-Ro antibody (anti-Ro 60 kD, anti-Ro 52 kD) specificity did not change in any of the patients during the follow-up period. CONCLUSION: Anti-Ro antibodies could represent a valuable indicator of disease activity in SS patients with cutaneous disorders. They do not, on the other hand, reflect disease activity in patients with SLE. The stable antibody profile in both SLE and SS patients supports the hypothesis that autoantibody production is predominantly genetically regulated.

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.