Autoantibodies to the major nucleolar phosphoprotein B23 define a novel subset of patients with anticardiolipin antibodies

Of 164 sera with antinucleolar antibodies, 7 (4.3%) were shown by Western blotting to react with a 37-kd polypeptide in a nuclear extract of HeLa cells and with the recombinant protein expressed by a complementary DNA clone encoding the major nucleolar protein B23. Six of the 7 sera (86%) had antibodies to cardiolipin (aCL), and the sample that was negative for aCL had had lupus anticoagulant on previous testing. All 7 patients had either systemic lupus erythematosus (SLE) or a variant of SLE, suggesting that anti-B23 identifies a subset of patients with SLE associated with a high frequency of aCL.     

Characterization of IgG monoclonal anti-cardiolipin/anti-beta2GP1 antibodies from two patients with antiphospholipid syndrome reveals three species of antibodies

Antiphospholipid antibodies (aPL), including antibodies detected in anti-cardiolipin (aCL) enzyme-linked immunosorbent assays and in lupus anticoagulant (LA) tests, are strongly associated with recurrent thrombosis and recurrent fetal loss, i.e. the antiphospholipid syndrome (APS). Although recent studies suggest that most APS-associated aCL are directed against the phospholipid (PL)-binding plasma protein beta2-glycoprotein 1 (beta2GP1), the precise nature of aCL binding specificities remains controversial. To address the issue of aCL specificity we generated five new monoclonal IgG aCL from two patients with APS. Characterization of these five aCL, as well as two previously published IgG aCL, revealed three patterns of reactivity: (1) four antibodies reacted strongly with human beta2GP1-cardiolipin (CL) complexes and weakly with human beta2GP1 alone; (2) two antibodies recognized bovine beta2GP1, but not human beta2GP1; (3) one antibody reacted with complexes of human beta2GP1 and CL, but not with human beta2GP1 alone. Only one monoclonal displayed weak LA activity. These patient-derived IgG monoclonal antibodies, and additional ones to be generated, may help define varying species of antibodies detected in aCL assays and identify the specific antibodies that may be pathogenic.     

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.     

Cross-reactivity of antiidiotypic antibodies with DNA in systemic lupus erythematosus

OBJECTIVE: To assess the functional relationship between antibodies reactive with DNA and antibodies reactive with the idiotypes (idiopeptides) of anti-DNA antibodies that are associated with systemic lupus erythematosus (SLE) in mice. METHODS: Antiidiotypic antibodies that appeared spontaneously in lupus mice, and others that were induced by immunization of normal, non-lupus mice, were analyzed for their reactivity by a range of direct binding, competition enzyme-linked immunosorbent assay (ELISA), and surface plasmon resonance (SPR) methods. Their reactions were assessed against synthetic peptides representing sequences of the V(H) region of anti-DNA monoclonal antibody (mAb) V-88, against the native mAb itself, and against mammalian DNA. RESULTS: In lupus mice, only sera with the highest reactivity against double-stranded DNA (dsDNA) also reacted with idiopeptides in ELISA, and this showed a strong statistical correlation. However, there was no significant relationship between antiidiotypic antibodies and anti-single-stranded DNA antibodies. Immunization of (BALB/c x NZW)F1 mice with idiopeptides p64 (V(H) residues 64-80) or p92 (V(H) residues 92-105) induced antibodies that reacted not only against the respective peptides, but also against the native parent anti-DNA mAb V-88. Furthermore, the immune antiidiopeptide antibodies cross-reacted with dsDNA. Competition SPR experiments with the BIAcore system supported this observation. The binding reaction of V(H) peptide p64 (representing the CDR-H2/FR-H3 region of V-88) with antiidiopeptide antibodies was inhibited by dsDNA. CONCLUSION: This study identified a unique set of autoantibodies in SLE. They react with both autoantibody idiotopes and with dsDNA, thus having a dual specificity for 2 autoantigens. Because these antiidiotope antibodies arise naturally during the development of lupus disease, and because they bind also to dsDNA, this provides a mechanism whereby the production of anti-dsDNA antibodies is stimulated. These idiotopes on autoantibodies in lupus act as natural mimotopes for inducing anti-dsDNA antibodies, which, due to their dual specificity, may significantly contribute to the pathology of nephritis in SLE.     

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.     

Identification of polyclonal and monoclonal antibodies against tissue plasminogen activator in the antiphospholipid syndrome

OBJECTIVE: To test the hypotheses that some plasmin-reactive anticardiolipin antibodies (aCL) may bind to tissue plasminogen activator (tPA) and that some of the tPA-reactive aCL may inhibit tPA activity. METHODS: We studied the reactivity of 8 patient-derived monoclonal aCL with tPA and examined the presence of IgG anti-tPA antibodies in patients with the antiphospholipid syndrome (APS). The effects of the reactive monoclonal aCL on the activity of tPA were also examined. RESULTS: Six patient-derived plasmin-reactive monoclonal aCL bound to tPA. Analysis of plasma samples revealed that 10 of 80 APS patients (12.5%) and 1 of 81 systemic lupus erythematosus patients (1.2%) had antibodies against fibrin-associated tPA, based on a cutoff value equal to the mean + 2SD of the level in 28 normal subjects. Of the 6 tPA-reactive monoclonal aCL, 2 of them (CL1 and CL15) inhibited tPA activity. CONCLUSION: Some of the plasmin-reactive aCL in APS patients may bind to tPA. Of the tPA-reactive aCL, some (such as CL1 and CL15) may inhibit tPA activity and, thus, may be prothrombotic in the host.     

Monoclonal antibodies to herpes simplex viruses antigens--specificity and utility in rapid serotyping of clinical isolates]

Sixteen hybridomas secreting antibodies to HSV-1 and 22 hybridomas secreting antibodies to HSV-2 were derived from fusion of SP2/0 myeloma cells with spleen cells from BALB/c mice immunized with each respective virus. Four of the former 16 hybridomas and seven of the latter 22 hybridomas were subcloned and injected into pristane-primed mice to obtain high titers of monoclonal antibodies. Antigen specificity of these monoclonal antibodies were determined by the Western blotting (WB) assay. Two out of four monoclonal antibodies that showed selective reactivity for HSV-1 in IFA, reacted with HSV-1 specific proteins; #1 reacted with 100 KD and 70 KD proteins and #4 with a 150 KD protein, respectively, while the remaining two antibodies reacted only with a 50 KD protein that is type-common antigen. On the other hand, two out of seven antibodies which showed selective reactivity for HSV-2 in IFA, reacted with HSV-2 specific proteins: #5 with a 100 KD protein and #10 with three proteins of 30, 25, and 20 KD, and the other two antibodies reacted with a 50 KD protein that is a type-common antigen. The remaining three antibodies, two of which were found to be immunoglobulin type IgM, reacted with neither HSV-1 nor HSV-2 antigens in WB assay. In order to determine their utility in serotyping, 11 monoclonal antibodies were examined by IFA test for reactivity to cells that were infected with 20 HSV-1 or 16 HSV-2 isolates which had been typed by neutralization test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma thrombomodulin and alpha 2-plasmin inhibitor-plasmin complex are elevated in active systemic lupus erythematosus.

Plasma levels of thrombomodulin and alpha 2-plasmin inhibitor-plasmin complex were measured by ELISA in patients with rheumatic diseases. Thrombomodulin levels in patients with active systemic lupus erythematosus (SLE) were significantly higher than those in patients with inactive SLE or in healthy controls. This suggests that thrombomodulin, normally a component of vascular endothelial cell membrane, is easily released to plasma in patients with active SLE. High titers of the thrombomodulin level and the correlated alpha 2-plasmin inhibitor-plasmin complex elevations imply vascular injury, and consequently, excessive fibrinolytic processes in active SLE.     

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     

Differential response of human and bovine platelets to bovine von Willebrand factor and vascular subendothelium

Human platelets undergo agglutination when stirred with bovine plasma (BP), but bovine platelets do not. The present study has shown that exposure of washed bovine platelets to subthreshold concentrations of adenosine diphosphate or thrombin before stirring restores their sensitivity to BP, and the cells undergo rapid agglutination. This agglutination was prevented by a monoclonal antibody, to glycoprotein GPIb. Flow cytometry studies revealed that exposure of bovine platelets to thrombin caused an increase in their ability to bind antibodies known to react with human GPIb or GPIIb-IIIa receptors. Interaction of bovine and human platelets with vascular subendothelium revealed additional differences in reactivity. Bovine platelets in citrate anticoagulant reacted poorly with subendothelium under flow conditions compared with human platelets. In contrast, bovine platelets in blood with low molecular weight heparin as anticoagulant adhered more readily than human cells. These findings suggest that different mechanisms are involved in hemostasis in human and bovine species.     

Differential response of human and bovine platelets to bovine von Willebrand factor and vascular subendothelium

Human platelets undergo agglutination when stirred with bovine plasma (BP), but bovine platelets do not. The present study has shown that exposure of washed bovine platelets to subthreshold concentrations of adenosine diphosphate or thrombin before stirring restores their sensitivity to BP, and the cells undergo rapid agglutination. This agglutination was prevented by a monoclonal antibody, to glycoprotein GPIb. Flow cytometry studies revealed that exposure of bovine platelets to thrombin caused an increase in their ability to bind antibodies known to react with human GPIb or GPIIb–IIIa receptors. Interaction of bovine and human platelets with vascular subendothelium revealed additional differences in reactivity. Bovine platelets in citrate anticoagulant reacted poorly with subendothelium under flow conditions compared with human platelets. In contrast, bovine platelets in blood with low molecular weight heparin as anticoagulant adhered more readily than human cells. These findings suggest that different mechanisms are involved in hemostasis in human and bovine species.     

Anti-endothelial cell antibodies to the endothelial hybridoma cell line (EAhy926) in systemic lupus erythematosus patients with antiphospholipid antibodies

The endothelial hybridoma (EAhy926) cell line was employed to clarify whether antiphospholipid antibodies (aPA) [lupus anticoagulant (LA), antiprothrombin antibody (aPT) and/or anticardiolipin antibody (aCL)] and anti-endothelial cell antibodies (AECA) are identical, and establish whether β₂-glycoprotein I (β₂-GPI) is needed for reactivity of aPA to endothelial cells. Ig-G AECA was positive in 9/30 SLE patients with aPA (30.0%) and 10/22 SLE patients negative for aPA (45.5%). Ig-M AECA was positive in one SLE patient with aPA and one SLE patient without aPA. AECA-positivity was not significantly different among unfixed, TNF-stimulated and fixed EAhy926. The influence of β₂-GPI on the reactivity of serum to EAhy926 was minimal, and absorption experiments of serum with cardiolipin-liposome/β₂-GPI or phosphatidylserine-liposome/prothrombin gave little evidence of cross-reactivity of aPA and AECA. The results of our study suggest that aPA and AECA may have partially cross-reacted, but were different antibodies. However, further study is needed to clarify the clinico-pathological significance of AECA.     

Serum thrombomodulin and anticardiolipin antibodies in patients with systemic lupus erythematosus.

Since thrombomodulin (TM) is a specific cell surface glycoprotein for vascular endothelial cells, serum TM (s-TM) might be a useful marker of endothelial cell damage. Antiphospholipid antibodies (aPL) frequently detected in systemic lupus erythematosus (SLE) have been associated with vascular occlusive diseases. Therefore we measured the s-TM in 60 patients with SLE, in 23 patients with other diseases including aPL (disease control group) and in 26 healthy subjects, by means of an enzyme immunoassay using monoclonal antibodies to human TM. A significant positive correlation was found between s-TM and serum creatinine levels in SLE patients (r = 0.813, p less than 0.001). When the s-TM level was divided by the serum creatinine level (TM/Cr) to exclude the effect of renal clearance, the TM/Cr ratios were significantly increased in SLE patients with active lupus nephritis (LN) compared to those without LN (p less than 0.05). The ratios did not correlate with the presence of aPL or antiphospholipid antibody syndrome (APLS) in SLE patients or in the disease control group, although a weak correlation between the TM/Cr ratios and IgG-anticardiolipin antibody titers was found in the SLE patients without LN (r = 0.449, p less than 0.01). The present results suggest that elevated TM/Cr ratios reflect renal and possibly extra-renal endothelial cell damage in SLE patients with active LN, but that s-TM levels do not associate with the presence of aPL or a history of APLS.     

Significance of anticardiolipin and anti-beta(2)-glycoprotein I antibodies in lupus nephritis

OBJECTIVE: To investigate whether anticardiolipin (aCL) and anti-beta(2)-glycoprotein I (anti-beta(2)GPI) antibodies are associated with lupus nephritis (group II patients), and whether there are differences in the prevalence of these two autoantibodies between group II patients and patients with non-nephritis SLE (group I) and primary antiphospholipid syndrome (PAPS) patients (group III). METHODS: IgG and IgM aCL were measured in 31 patients and anti-beta(2)GPI in 30 patients with systemic lupus erythematosus (SLE) nephritis and 25 without SLE nephritis and in 36 PAPS patients by validated enzyme immunoassays. Relationships of anti-double-stranded DNA (anti-dsDNA) antibodies and antibodies to the collagenous region of C1q (anti-C1q) with SLE nephritis were also examined. RESULTS: The prevalence and levels were higher for aCL, but not for anti-beta(2)GPI, antibodies in group II than in group I patients. Absolute values of aCL and anti-beta(2)GPI in all three patient groups correlated with each other. The prevalences of aCL, anti-dsDNA and anti-C1q antibodies were significantly higher in group II than in group I and group III patients. CONCLUSION: The observations in this paper suggest that raised levels of aCL antibodies are associated with lupus nephritis. We were not able to demonstrate an association between anti-beta(2)GPI antibodies and kidney disease either in patients with lupus or in patients with primary antiphospholipid syndrome. In SLE, we demonstrated that the presence of anticardiolipin antibodies in conjunction with elevated levels of anti-dsDNA and anti-C1q antibodies is highly specific for glomerulonephritis in patients with lupus.     

Autoreactive IgG memory antibodies in patients with systemic lupus erythematosus arise from nonreactive and polyreactive precursors

Persistent autoantibody production in patients with systemic lupus erythematosus (SLE) suggests the existence of autoreactive humoral memory, but the frequency of self-reactive memory B cells in SLE has not been determined. Here, we report on the reactivity of 200 monoclonal antibodies from single IgG+ memory B cells of four SLE patients. The overall frequency of polyreactive and HEp-2 self-reactive antibodies in this compartment was similar to controls. We found 15% of IgG memory B cell antibodies highly reactive and specific for SLE-associated extractable nuclear antigens (ENA) Ro52 and La in one patient with serum autoantibody titers of the same specificity but not in the other three patients or healthy individuals. The germ-line forms of the ENA antibodies were non-self-reactive or polyreactive with low binding to Ro52, supporting the idea that somatic mutations contributed to autoantibody specificity and reactivity. Heterogeneity in the frequency of memory B cells expressing SLE-associated autoantibodies suggests that this variable may be important in the outcome of therapies that ablate this compartment.     

Newer insights on the mechanism of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) type II is a complex clinical syndrome. It is an immune reaction to heparin in which the formation of antibodies targeted against the heparin-platelet factor 4 complex results in platelet activation. Platelet activation plays a central role in HIT; however, platelet activation does not occur as an isolated physiologic response. To elucidate further the mechanism of thrombogenesis in HIT, we undertook studies to determine the effect of heparin antibodies on endothelial cells, leukocytes, and the inflammatory state. We summarize our previous and new findings. For endothelial cells: Antiheparin antibodies bind to and directly activate microvascular endothelial cells, whereas binding to and activating macrovascular endothelial cells requires preactivation by platelets or tumor necrosis factor alpha (TNFalpha). Increased circulating levels of hemostatic activation factors as observed with thrombosis, particularly soluble P-selectin, plasminogen activator inhibitor type 1 (PAI-1), tissue factor, and thrombomodulin, were associated with endothelial cell activation and were also found in the blood circulation of patients with HIT. For the inflammatory state: Neutrophils and monocytes (but not lymphocytes) bind to and form complexes with platelets in the presence of HIT antibodies. Activated monocytes bind to endothelial cells and produce a procoagulant state. Patients with HIT have an increased level of cytokines in their blood circulation. For HIT antibodies: Only heparin fractions larger than 5 kd interacted with HIT antibodies, explaining why low-molecular-weight heparin (LMWH) usually does not generate antibodies. HIT antibodies are heterogeneous in structure, affinity, and specificity. These data suggest that, in addition to the platelet component, several other mechanisms are associated with the pathophysiology of HIT. These include an inflammatory state, endothelial cell remodeling, and the known procoagulant state. Differences between patients in the levels of the inflammatory markers may relate to various stages of the inflammatory/procoagulant state that exists in patients with HIT. The variations within the HIT antibodies may influence their ability to activate platelets, endothelial cells, and leukocytes, and thus contribute further to the variations in the pathogenicity of HIT.     

Human prostate specific and shared differentiation antigens defined by monoclonal antibodies.

Splenic lymphocytes of BALB/c mice immunized with membrane-enriched fractions of human benign prostatic hyperplasia tissues were fused with the NS-1 light chain-secreting murine myeloma cell line. This generated hybridoma cultures that secreted immunoglobulins reactive in solid-phase radioimmunoassays with membrane preparations of prostatic tissues but not with membrane preparations of apparently normal human liver, spleen, thymus, or erythrocytes. After further screening of immunoglobulin reactivities and cloning of cultures, eight monoclonal antibodies were chosen that demonstrated reactivity with human prostate tissues. These monoclonal antibodies could be placed into at least three major groups--epithelium-specific, polyepithelial, and stroma-specific--on the basis of differential binding to the surfaces of various component cells in the prostate and other epithelia. Two antibodies defined unique protein antigens specific for prostate epithelia that were not crossreactive with prostatic acid phosphatase or the recently described "prostatic antigens." These antibodies also detected antigens on malignant prostate tissues as well as other malignant tissues. Four antibodies defined three unique polyepithelial protein antigens (two of the antibodies were different isotypes defining the same protein). Each of the polyepithelial antigens was expressed on a different spectrum of normal epithelial tissues. Two displayed brain tissue crossreactivity, one was present on pancreas, and one was present on platelets. The two antibodies that detected prostatic stromal protein antigens showed different spectra of reactivities. One antibody reacted with apparently all prostatic stromal cells as well as endothelial cells in the prostate and other organs. The other antibody apparently reacted with all prostatic stromal cells as well as myoepithelial and muscle cells in other organs.     

Prevalence of antiphospholipid antibodies in systemic sclerosis and association with primitive pulmonary arterial hypertension and endothelial injury

OBJECTIVE: To investigate the prevalence and clinical significance of antiphospholipid antibodies in patients with systemic sclerosis (SSc). METHODS: Autoantibodies against cardiolipin (aCL) and beta2-glycoprotein 1 (beta2-GPI) were detected by enzyme-linked immunoabsorbent assays (ELISAs) in successively hospitalised SSc patients admitted during a 24-month period. These patients were compared to patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA). RESULTS: 108 SSc patients were included: 61 had limited cutaneous SSc, 47 had the diffuse sub-type, 16 had primitive pulmonary arterial hypertension (PAH) and 34 had digital ulcerations. The control groups consisted of 37 RA and 38 SLE patients. The prevalence of aCL positivity was lower in SSc patients vs SLE patients (14 vs 47%; p < 0.001), lower in RA patients vs SLE patients (19 vs 47%; p < 0.001), and not different in SSc vs RA patients (14 vs 19%; NS). The mean aCL titer was also lower in SSc vs SLE patients (8+/-10 vs 15+/-20; p < 0.001). In SSc patients, positivity for aCL was associated with PAH (p = 0.009) and the aCL titer correlated with that of the von Willebrand antigen factor (r= 0.23; p = 0.045). The prevalence of anti beta2-GPI positive patients (IgG and/or IgM) was 5% in the SSc group, 18% in the SLE group and 5% in the RA group (SLE vs SSc and SLE vs RA; p = 0.005). CONCLUSION: We found that the prevalence of antiphospholipid antibodies in SSc patients was low. However, aCL antibodies were associated with PAH and endothelial injury.     

Antiphospholipid antibodies (aPL) in systemic lupus erythematosus. Are they specific tools for the diagnosis of aPL syndrome?

OBJECTIVE--Antiphospholipid antibody (aPL) specificity for aPL-related events was evaluated in systemic lupus erythematosus (SLE). METHODS--A study was carried out on 105 patients affected with SLE comparing the prevalence of lupus anticoagulant (LA) and IgG and IgM anticardiolipin antibodies (aCL) between patients with and without features of antiphospholipid syndrome (APS). Antiphospholipid antibody profile was subsequently evaluated in the aPL positive patients with and without aPL-related events, thus excluding the patients with complications of APS possibly due to factors other than aPL. RESULTS--LA showed a strong association with thrombosis and livedo reticularis, and IgG aCL with thrombosis and neurological disorders, while no clinical features were associated with IgM aCL. A considerable number of aPL positive patients with no aPL-related manifestations was also observed, suggesting the low specificity of aPL assays (54.4%). When studying the 60 aPL positive patients, LA was specific (91.3%) for the diagnosis of aPL-related thrombosis, whereas aCL were not specific, although IgG aCL mean levels were higher in patients with arterial thrombosis than in those without APS features. CONCLUSIONS--LA but not aCL positivity is a specific tool for the diagnosis of thrombotic complications due to aPL in SLE.