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E N Harris

Publications and source records attributed to E N Harris.

At least 37 records · Page 2Linked to original sources
PubMed1999

Leukocyte-endothelium interaction in arterioles after ischemia and reperfusion.

Leukocyte-endothelium interaction in postcapillary venules plays an important role in reperfusion injury, inflammation, shock, and sepsis. This phenomenon is poorly described in precapillary arterioles. In fact, many researchers have reported no evidence of leukocyte adherence in arterioles whatsoever. Most research has focused on venules of larger rodents, in which observation of the microcirculation, especially arterioles, is limited. We have developed a model which provides a clearer view of these microvessels using the mouse cremaster muscle. This muscle has an approximate thickness of 100 microm allowing images produced by transillumination to be very clear. After vascular isolation, the right cremaster muscle was subjected to 4 h of ischemia, followed by 2 h of reperfusion. The left muscle was not rendered ischemic, thereby allowing it to serve as the animal's own internal control. We observed leukocyte rolling in arterioles in both the ischemic and the nonischemic muscles. Leukocyte sticking was seen in arterioles and venules on both sides, except in control arterioles. The number of rolling and sticking leukocytes on the ischemic side was significantly higher than in controls (P < 0.05) for both arterioles and venules. During the reperfusion period, this number did not change significantly. Transmigration of leukocytes was observed only in venules, but not in arterioles. The number of perfused capillaries was reduced on the ischemic side compared to controls and did not change significantly during the 2 h of reperfusion. Our results demonstrate that leukocyte-endothelium interaction occurs in muscle arterioles of mice. This phenomenon is more pronounced after ischemia and reperfusion, i.e., depends on the extent of tissue insult.

Animals↗
PubMed1999

Pregnancy complicated by the antiphospholipid syndrome: outcomes with intravenous immunoglobulin therapy.

OBJECTIVE: To assess maternal and fetal outcomes in 15 patients with antiphospholipid syndrome (19 pregnancies) treated with intravenous immunoglobulin (IV Ig) during pregnancy. METHODS: Monthly IV Ig therapy was initiated in the first or early second trimester of all pregnancies except two. Additional therapy consisted of low-dose aspirin and subcutaneous heparin. Six patients also received steroid therapy. Serial anticardiolipin IgG levels were measured in eight pregnancies. RESULTS: The live-birth rate was 84% (16 of 19 live births), and there were three pregnancy losses. There were no cases of fetal growth restriction (FGR). Preeclampsia and nonreassuring fetal status were each diagnosed in 25% of the pregnancies. Seventy-five percent of the infants were delivered at 34 weeks' gestation or later. Anticardiolipin IgG decreased throughout the course of therapy in seven pregnancies. Placental pathology was minimal. CONCLUSION: Pregnancy complications appear to be minimized with the use of IV Ig. Definitive recommendations regarding the use of IV Ig in pregnancy await the conclusion of randomized trials. If the combination of IV Ig, aspirin, and heparin significantly decreases the incidences of FGR and prematurity, it may be a cost-effective primary therapy for pregnancies complicated by the antiphospholipid syndrome.

Adult↗
PubMed1999

Comparison between the standard anticardiolipin antibody test and a new phospholipid test in patients with connective tissue diseases.

OBJECTIVE: Antiphospholipid (aPL) antibodies are present in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibody syndrome (APS) and are associated with recurrent thromboses, thrombocytopenia, and pregnancy losses. The presence of aPL antibodies is routinely tested using a standardized ELISA that utilizes cardiolipin as antigen (aCL ELISA). This test, although sensitive, is frequently positive in patients with nonrelated autoimmune disorders and some infectious diseases, making the test less specific. Thus there is a need for more specific tests for aCL with equivalent sensitivity to the standard assay. We evaluated the diagnostic utility of a new aPL antibody test kit with a unique phospholipid mixture designed to be more specific than the standard anticardiolipin ELISA. METHODS: aPL antibodies (IgG, IgM) were measured by both a standard ELISA and a new ELISA kit (APhL ELISA Kit, Louisville APL Diagnostics, Inc., Louisville, KY, USA) in the baseline serum from patients enrolled in a 5 year inception cohort, prospective study of early rheumatoid diseases: rheumatoid arthritis (N = 70), SLE (70), scleroderma (45), inflammatory myositis (36), and early undifferentiated connective tissue disease (CTD) (165). Diagnosis was based on standardized criteria and determined at the last study visit. A nested group of patients with Sjogren's syndrome (44) was also defined. Serum from 200 blood donors (BD) served as controls. Patients with known APS (33) and antinuclear cytoplasmic antibody positive renal vasculitis (52) were also studied. Laboratory personnel were blinded to sample diagnostic group. RESULTS: The kit was 90.9% sensitive for detecting APS. Seven patients missed by the kit all had standard aCL values < 40 PL units. Assuming controls do not have APS, the kit was 99.5% specific vs 96.0% for the standard assay. For the patients with CTD, the kit never detected a patient that was not also detected by the standard aCL assay. CONCLUSION: The APhL ELISA Kit appears to be more specific than the standard aCL ELISA without adding potential false positive results. The new test may be useful for followup study for patients found to be aCL positive by standard assays to increase specificity for aCL screening.

Antibodies, Anticardiolipin↗
PubMed1999

A flow cytometric assay for the detection of antiphospholipid antibodies.

The data and the results obtained at the above symposium show that the flow cytometric method closely correlates with the standardized aCL bench ELISA and with the APhL ELISA kit. The aCL/aPS FACS kit is comparable in sensitivity to the APhL ELISA kit and standard aCL bench ELISA, but the aCL/aPS FACS kit is more specific than the standard anticardiolipin assay (particularly for the determination of aPS). In summary, the aCL/aPS FACS kit enables rapid (total run time < or = 1 hr) and simultaneous determination of aCL (aCL) and anti-PS antibodies of the IgG and IgM classes and combines good sensitivity and specificity in a single assay. The method is reproducible (intraassay variations < 5%). Furthermore, it is easy to transform into a partially or fully mechanized process and is well suited for laboratories that test large numbers of samples daily. The assay promises to be useful not only for detecting positive APS sera, but also in evaluating the significance of phospholipid specificity and antibody isotypes in patients with APS.

Antibodies, Anticardiolipin↗
PubMed1998

Utilization of intravenous immunoglobulin therapy to treat recurrent pregnancy loss in the antiphospholipid syndrome: a review.

Although experience is still limited, intravenous immunoglobulin therapy for recurrent pregnancy loss in the Antiphospholipid Syndrome (APS) may represent a significant advance. APS was widely recognized only fifteen years ago. Pregnancy loss and thrombosis are the prominent clinical features. Initially, prednisone was used for treatment of pregnancy loss, but matemal and fetal complications stimulated searches for alternative therapy. Subcutaneous heparin and low dose aspirin was next utilized, but although efficacious, there is still a 30% failure rate, and intrauterine growth retardation, prematurity, and pre-eclampsia are relatively frequent. In the late 1980's, there were a number of case reports of successful pregnancy outcomes after treatment with intravenous immunoglobulin (IVIg) but regimens differed. Series from two centers have confirmed these initial findings and treatment regimens have become more consistent. Both centers have reported success with doses of 400 mg/kg/day for 5 days or 1 g/kg/day for two days each month initiated during the first or early second trimester. Success rates of 70-100% have been reported, and complications such as pre-eclampsia, intrauterine growth retardation, and premature births appear reduced, when compared to prednisone and low dose aspirin or heparin and low dose aspirin. Several patients who were treated with IVIg also received heparin, making it uncertain whether heparin may also need to be added to IVIg. Intravenous immunoglobulin is safe, but expensive. Despite its expense, if IVIG is shown to markedly decrease matemal and fetal morbidity, it may be the logical treatment of choice to prevent pregnancy loss in APS.

Abortion, Habitual↗
PubMed1998

Diagnosis of the antiphospholipid syndrome: a proposal for use of laboratory tests.

The presence of antiphospholipid (aPL) antibodies has been associated with thrombosis, pregnancy loss and thrombocytopenia in the antiphospholipid syndrome (APS). The anticardiolipin and the lupus anticoagulant tests are frequently used to detect aPL antibodies. The anticardiolipin ELISA utilizes cardiolipin coated on polystyrene plates as antigen and is a very sensitive test but lacks specificity, since it can be positive in a number of infectious (such as syphilis, HIV) and autoimmune diseases other than APS. In an effort to improve specificity, new ELISA techniques that employ alternative antigens (such as beta2-glycoprotein 1, particularly when coated onto oxidized microtiter plates or mixture of phospholipids) have been developed. Several investigators have reported that these new assays enable more specific determination of aPL antibodies and thus can be used more reliably for the diagnosis and confirmation of APS. This article examines the results of those studies, including data that shows correlations of these assays with clinical manifestations of APS, and proposes a new protocol for the use of laboratory tests in the diagnosis of APS.

Abortion, Habitual↗
PubMed1998

Thrombogenic properties of antiphospholipid antibodies do not depend on their binding to beta2 glycoprotein 1 (beta2GP1) alone.

Immunization of mice with beta2glycoprotein 1 (beta2GP1) induces production of antiphospholipid (aPL) antibodies, which were shown to have thrombus enhancing properties in an experimental mouse model, indicating that these antibodies are thrombogenic in vivo. To determine whether the thrombogenic effect of murine antiphospholipid antibodies is due to their aPL or their anti-beta2GP1 activity, we injected mice with murine monoclonal anticardiolipin (aCL) and anti-beta2GP1 antibodies. Effects of these antibodies on thrombus formation, was evaluated utilizing a mouse model which enables kinetics of thrombus formation to be studied. The results of this study showed that the size of the thrombus in animals injected with murine aCL antibodies was larger than that in control groups. There was no difference in thrombus kinetics between anti-beta2GP1 injected mice and controls, suggesting that the thrombogenic effect of aPL antibodies is not related to their anti-beta2GP1 activity alone. Mice receiving monoclonal antibodies with both aCL and anti-beta2GP1 activity, also increase thrombus size when compared with controls. These data indicate that murine aCL, but not anti-beta2GP1, antibodies are thrombogenic in vivo.

Animals↗
PubMed1997

Hydroxychloroquine reverses thrombogenic properties of antiphospholipid antibodies in mice.

BACKGROUND: Previous studies have demonstrated that human monoclonal and polyclonal anticardiolipin antibodies have thrombogenic properties in vivo. Using such a model in which these antibodies have been shown to increase both the size of an induced thrombus and the duration of time in which such a clot lasts, we investigated whether hydroxychloroquine alters the dynamics of such thrombus formation. METHODS AND RESULTS: Three groups of nine mice were injected with purified immunoglobulin G (IgG) from a patient with the antiphospholipid syndrome (IgG-APS) and then fed with hydroxychloroquine at various doses (100, 6, and 3 mg/kg body wt). Three control groups of mice were also studied, including mice injected with IgG-APS and then fed with placebo, as well as two other groups injected with IgG from normal human serum and fed either hydroxychloroquine or placebo. A standardized thrombogenic injury was subsequently induced in the femoral vein of each mouse and the area (size) of thrombus measured as well as the total period of time that thrombus was present. Mice treated with hydroxychloroquine and IgG-APS showed significantly smaller thrombi that persisted for a shorter period of time compared with animals treated with IgG-APS and placebo. CONCLUSIONS: Hydroxychloroquine significantly diminished both thrombus size and total time of thrombus formation in mice previously injected with IgG-APS.

Animals↗
PubMed1997

A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis.

BACKGROUND: Antiphospholipid syndrome (APS) is a disorder of recurrent venous or arterial thrombosis, pregnancy losses, and thrombocytopenia. Recurrent thrombosis has particularly adverse effects on patients prognosis. The factors that influence recurrence and management techniques that prevent these events remain controversial. To add further insight regarding predisposing factors and the prevention of thrombotic recurrence, 61 well-characterized patients with APS were followed up for a median time of 77 months. METHODS: A retrospective cohort study was conducted in which the following factors were examined to determine their influence on thrombotic recurrence: primary vs secondary syndrome; the presence of hypertension, hyperlipidemia, diabetes, or smoking; patient age, sex, and race; pregnancy and oral contraceptives use; and treatment with warfarin sodium, warfarin plus aspirin, aspirin alone, prednisone, or no treatment. RESULTS: There was no difference between patients with primary and secondary APS with respect to recurrent arterial (55% vs 38%, respectively) or recurrent venous (47% vs 50%, respectively) thrombotic events. In all patients with APS, white race (P = .02) was associated with recurrent arterial events. Venous thrombosis occurred during pregnancy or in the postpartum period in 16 (30%) of 53 women and in 8 women taking oral contraceptives. Recurrent arterial and venous thromboses were significantly decreased with prophylactic warfarin use when compared with prednisone use or no treatment. Recurrences were infrequent in patients with prothrombin ratios of 1.5 to 2.0. CONCLUSIONS: Treatment with warfarin was most effective in preventing recurrent arterial and venous thrombosis. Pregnancy and the use of oral contraceptives or prednisone may also influence recurrence.

Adult↗
PubMed1997

Antiphospholipid antibodies and cerebral lupus.

Antiphospholipid antibodies probably play a minor role in cerebral lupus. They are associated primarily with stroke and transient ischemic attacks, which occur only in a minority of patients with central nervous system complications of SLE. However, ready demonstration of functional effects of antiphospholipid antibodies in the coagulation system as well as persuasive evidence that they can induce thrombosis and pregnancy loss in experimental mice lend credence to the belief that many autoantibodies play a direct role in disease pathogenesis. Hence the role of the many autoantibodies associated with CNS lupus is a legitimate field of inquiry. This review outlines the history of antiphospholipid antibodies, discusses the controversy concerning antiphospholipid antibody specificity, summarizes recent experimental data on their functional effects in the coagulation system, and describes animal models of the antiphospholipid syndrome in which antibodies with cardiolipin-binding activity have been shown to play a direct role in thrombosis and pregnancy loss.

Animals↗
PubMed1997

Pathogenic antibodies in women with obstetric features of antiphospholipid syndrome who have negative test results for lupus anticoagulant and anticardiolipin antibodies.

OBJECTIVE: Our goal was to determine whether women with clinical features of antiphospholipid syndrome but negative test results for lupus anticoagulant and anticardiolipin antibodies have pathogenic antibodies not identified by currently used methods. STUDY DESIGN: Sera were obtained from women with clinical features associated with antiphospholipid antibodies who had negative test results for lupus anticoagulant and anticardiolipin antibodies (antiphospholipid syndrome-like). We studied (1) the effect of passive immunization with their purified immunoglobulin G fraction on murine pregnancy (n = 35) and (2) the presence of antiphospholipid antibodies other than lupus anticoagulant or anticardiolipin antibodies (n = 39). Sera were also retested for anticardiolipin antibodies and lupus anticoagulant. RESULTS: Fetal loss occurred in 235 of 1088 (22%) pups in 137 mice immunized with immunoglobulin G fraction from antiphospholipid syndrome-like women compared with 23 of 402 (6%) pups in 53 control mice. Immunoglobulin G from 11 study patients resulted in the loss of at least one third of the exposed pups. Five women had positive levels of antiphosphatidylserine antibodies (>99th percentile). All levels were low positive, and three women also had low-positive levels of anticardiolipin antibodies on repeat testing. Five of the 11 (45%) women whose immunoglobulin G fractions caused at least 33% fetal loss also had positive test results for antiphospholipid antibodies. CONCLUSIONS: A subset of women with clinical disorders suspicious for antiphospholipid syndrome but who had negative test results for lupus anticoagulant and anticardiolipin antibodies by current methods have serum immunoglobulin G that is pathogenic to murine pregnancy. Testing for pathogenic immunoglobulin G may provide additional means to identify women with an as yet uncharacterized immune condition. The clinical relevance of low levels of antiphospholipid antibodies in these women remains unproved.

Abortion, Habitual↗
PubMed1997

Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome.

OBJECTIVE: To determine whether antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin are associated with recurrent pregnancy loss. METHODS: Sera from three groups of women were studied: 1) 147 women with recurrent pregnancy loss but no clinical signs or symptoms of autoimmune disease who tested negative for lupus anticoagulant and medium-to-high levels of immunoglobulin G anticardiolipin antibodies; 2) 104 healthy, fertile controls of similar age and gravidity; and 3) 43 women with well-characterized antiphospholipid syndrome. Serum antibody binding against six phospholipids (cardiolipin, phosphatidic acid, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol) was determined using enzyme-linked immunoassays, and results were normalized using an anticardiolipin standard. RESULTS: Twenty-six (18%) women with recurrent pregnancy loss and nine (9%) controls tested positive (above the 99th percentile) for antiphospholipid antibodies. Sera from five (3.4%) women with recurrent pregnancy loss and four (3.8%) controls demonstrated binding to phospholipid antigens other than cardiolipin. In contrast, binding to phospholipid antigens was demonstrated in sera from more than 90% of women with antiphospholipid syndrome. Among women testing positive for antiphospholipid antibodies, the median positive value for women in the antiphospholipid syndrome group was significantly higher than for those with recurrent pregnancy loss or normal fertile controls. CONCLUSIONS: Women with recurrent pregnancy loss are no more likely than fertile controls to have elevated levels of antiphospholipid antibodies once lupus anticoagulant, anticardiolipin, and an obvious clinical history of autoimmune disease have been excluded. Testing for antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin is not clinically useful in the evaluation of recurrent pregnancy loss.

Abortion, Habitual↗
PubMed1997

Antiphospholipid antibody: functional specificity for inhibition of prothrombin activation by the prothrombinase complex.

The antiphospholipid syndrome (APS) is associated with production of autoantibodies with lupus anticoagulant (LA) activity. These antibodies cause prolongation of in vitro clotting tests by inhibition of the conversion of prothrombin to thrombin in the presence of anionic phospholipid (PL). The extent to which this inhibition reflects antibody binding to, or functional inhibition of, phospholipids alone, prothrombin alone, or a prothrombin-phospholipid complex is pertinent to our understanding of the pathophysiology of this syndrome. Immunoglobulin fractions (IgG) from 18 patients with LA activity were tested for inhibitory activity against prothrombin activation by either factor Xa, in a purified prothrombinase system, or by purified fractions of snake venoms (E. carinatus, E. multisquamatus) which cleave prothrombin at the same initial site as the prothrombinase complex but do not require anionic phospholipid as a cofactor. Parallel testing of the same IgG samples for prothrombin binding by immunoassay was performed. Although all IgG samples inhibited the prothrombinase reaction, only three exhibited any inhibition of venom protease prothrombin activation in either the presence or absence of PL. Only one sample exhibited prothrombin binding by Western blot. These results suggest that lupus anticoagulant antibodies are heterogenous and that many, if not most, of the autoantibody populations responsible for LA activity impair prothrombin activation by interaction either with phospholipid alone or with a restricted range of prothrombin-phospholipid epitopes expressed by prothrombin only as part of the intact prothrombin-prothrombinase complex.

Antibodies, Anticardiolipin↗
PubMed1996

Thrombogenic properties of murine anti-cardiolipin antibodies induced by beta 2 glycoprotein 1 and human immunoglobulin G antiphospholipid antibodies.

BACKGROUND: Recurrent arterial thrombosis and venous thrombosis are frequent complications of the antiphospholipid syndrome (APS). Patients produce anti-cardiolipin antibodies, but the role of these antibodies in thrombus formation is uncertain. This study used a unique CD-1 mouse model of thrombosis to determine whether anti-cardiolipin and anti-beta 2 glycoprotein 1 (beta 2 GP1) antibodies induced immunologically in these animals are thrombogenic. METHODS AND RESULTS: The CD-1 mouse model enables measurement of the kinetics of a thrombus induced in the femoral vein of the animal. Animals are first anesthetized, then one femoral vein is exposed and subjected to a standardized, nonpenetrating "pinch" injury that induces a thrombus. The vein is trans-illuminated, and the growing thrombus is visualized on a television screen. The rate of formation and disappearance of the thrombus as well as its area can be measured by a computer attached to the television. Three groups of CD-1 mice (each group comprising seven animals) were studied. Group 1 mice were actively immunized with beta 2GP1, resulting in production of anti-beta 2GP1 and anti-cardiolipin antibodies. Group 2 mice were actively immunized with human immunoglobulin G (IgG) anti-cardiolipin antibodies and produced anti-human IgG as well as anti-cardiolipin antibodies (the latter by an idiotype-anti-idiotype reaction). These animals did not produce anti-beta 2GP1 antibodies. Group 3 mice were immunized with human serum albumin (HSA) and produced anti-HSA but not anti-cardiolipin antibodies. The kinetics of thrombus formation induced in the femoral veins of the experimental mice were compared. Results showed that the mean thrombus area as well as mean time during which thrombi persisted were significantly greater in group 1 and group 2 mice compared with group 3. There was no statistical difference between group 1 or group 2. CONCLUSIONS: Demonstration of a thrombogenic effect of murine anti-cardiolipin antibodies suggests that these antibodies may be pathogenic in humans with APS.

Animals↗
PubMed1996

A monoclonal IgG anticardiolipin antibody from a patient with the antiphospholipid syndrome is thrombogenic in mice.

Antiphospholipid antibodies, including anticardiolipin antibodies (ACA), are strongly associated with recurrent thrombosis in patients with the antiphospholipid syndrome (APS). To date, reports about the binding specificities of ACA and their role(s) in causing and/or sustaining thrombosis in APS are conflicting and controversial. The plasmas of patients with APS, usually containing a mixture of autoantibodies, vary in binding specificity for different phospholipids/cofactors and vary in in vitro lupus anticoagulant activity. Although in vivo assays that allow assessment of the pathogenic procoagulant activity of patient autoantibodies have recently been developed, the complex nature of the mixed species prevented determination of the particular species responsible for in vivo thrombosis. We have generated two human IgG monoclonal ACA from an APS patient with recurrent thrombosis. Both bound to cardiolipin in the presence of 10% bovine serum, but not in its absence, and both were reactive against phosphatidic acid, but were nonreactive against purified human beta-2 glycoprotein 1, DNA, heparan sulfate, or four other test antigens. Both monoclonal autoantibodies lacked lupus anticoagulant activity and did not inhibit prothrombinase activity. Remarkably, one of the monoclonal antibodies has thrombogenic properties when tested in an in vivo mouse model. This finding provides the first direct evidence that a particular antiphospholipid antibody specificity may contribute to in vivo thrombosis.

Adult↗
PubMed1996

The prevalence and clinical associations of anticardiolipin antibodies in a large inception cohort of patients with connective tissue diseases.

PURPOSE: To determine the prevalence and clinical associations of anticardiolipin antibodies (aCL) in a blinded, controlled study of patients with a variety of connective tissue diseases (CTD) using a standardized aCL testing system. PATIENTS AND METHODS: Anticardiolipin antibodies (IgG, IgM, and IgA) were measured by direct enzyme-linked immunosorbent assay (ELISA) in the baseline serum samples of patients enrolled in a Cooperative Study of Systematic Rheumatic Diseases (CSSRD), National Institutes of Health (NIH) supported, 5-year inception-cohort, prospective study of early rheumatic diseases: rheumatoid arthritis (RA, n = 70), systemic lupus erythematosus (SLE, n = 70), scleroderma (PSS, n = 45), myositis (PM/DM, n = 36), and early undifferentiated connective tissue disease (EUCTD, n = 165). Diagnosis was based on standardized criteria and determined at the last study visit. A nested group of patients with Sjögren's syndrome (SJ, n = 44) was also defined. Serum from 200 blood donors (BB) served as controls. Additional patients with known antiphospholipid syndrome (APS, n = 33) and ANCA-related renal vasculitis (ANCA, n = 52) were also studied. Laboratory personnel were blinded to sample diagnostic group. RESULTS: The prevalence of either IgG or IgM aCL among each diagnostic group was RA 15.7%, SLE 15.76%, PSS 6.7%, PM/DM 8.3%, EUCTD 9.1%, SJ 6.8%, ANCA 3.8%, and BB controls 4.0%. Prevalence of aCL was significantly different for both the RA and SLE groups versus BB controls (P < 0.01) but not among other diagnostic groups. Only 2 study patients had positive tests for IgA aCL (1 with PM/DM and 1 with EUCTD) versus 15% of APS with positive IgA aCL. Study patients positive for IgG or IgM aCL were significantly more likely to have hemolytic anemia or a positive serologic test for syphilis and less likely to have Raynaud's phenomenon. However, no associations were found between aCL positivity and thrombocytopenia, seizures, renal insufficiency, presence of a positive antinuclear antibody or rheumatoid factor, subcutaneous nodules or digital ulcers. CONCLUSIONS: Based on results from this large CSSRD inception cohort, anticardiolipin antibodies are present in approximately 16% of patients with RA or SLE but are less common in patients with PSS, PM/DM, EUCTD, SJ, and ANCA vasculitis, where their prevalence approaches that in the normal population. Few consistent clinical association can be found among patients with CTD who are aCL positive. The complete diagnostic and prognostic importance and specificity of these antibodies remains to be fully determined.

Antibodies, Anticardiolipin↗
PubMed1996

Studies on the interaction of placental anticoagulant protein I, beta 2 glycoprotein 1, and antiphospholipid antibodies in the prothrombinase reaction and in the solid phase anticardiolipin assays.

Recently it has been suggested that antiphospholipid antibodies may not be specific for phospholipids but directed to beta2glycoprotein 1 (beta2GP1), phospholipid-beta2GP1 complexes, prothrombin, or prothrombin-phospholipid complexes. To explore this issue further, we examined the influence of two phospholipid binding proteins, annexin V (placental anticoagulant protein I (PAP I)) and beta2GP1, on the activity of immunoglobulin G (IgG) fractions from patients with antiphospholipid syndrome (APS), both in the prothrombin-thrombin conversion assay and in the anticardiolipin enzyme-linked immunosorbent assay (ELISA). Results showed that each of eight IgG-APS; fractions, as well as PAP I and beta2GP1, individually inhibited the prothrombinase reaction. When IgG-APS samples were combined with PAP I or beta2GP1, or both PAP I and beta2GP1, inhibition of the prothrombinase reaction was additive. In the anticardiolipin ELISA, PAP I inhibited IgG-APS binding to cardiolipin, but beta2GP1 enhanced IgG-APS binding to cardiolipin. The "enhancing" effect of beta2GP1 in the ELISA system was neutralized by PAP I, an effect partially overcome by increasing the concentration of beta2GP1. Similar results were observed when affinity-purified anticardiolipin antibodies were used in place of whole IgG-APS preparations. These data indicate that IgG preparations obtained from the 8 patients with APS recognize similar epitopes; on anionic phospholipids in the anticardiolipin test and in the prothrombin-thrombin conversion assay. These data do not exclude the possibility that the IgG preparations may bind prothrombin-phospholipid or beta2GP1-phospholipid complexes.

Annexin A5↗