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Strong correlation between the prevalence of cerebral infarction and the presence of anti-cardiolipin/beta2-glycoprotein I and anti-phosphatidylserine/prothrombin antibodies--Co-existence of these antibodies enhances ADP-induced platelet activation in vitro.

Cerebral infarction is the most common arterial thromboembolic complication in the anti-phospholipid antibodies (aPL) syndrome. In an effort to clarify the roles of aPL in the pathogenesis of cerebral infarction in patients with SLE, we examined the levels of anti-cardiolipin/2-glycoprotein I antibodies (anti-CL/beta2-GPI) and anti-phosphatidylserine/prothrombin anti-bodies (anti-PS/PT) in addition to lupus anticoagulant (LA) activity in 126 patients with SLE (35 with cerebral infarction and 91 without thrombosis). Both anti-CL/beta2-GPI and anti-PS/PT strongly correlated with the presence of LA activity. The prevalence of cerebral infarction was obviously higher in the patients who had both anti-CL/beta2-GPI and anti-PS/PT (76.5% [26/34 cases], p<0.0001) than in the other patients having anti-CL/beta2-GPI or anti-PS/PT alone or neither of them (9.8% [9/92 cases]). Furthermore, we studied the in vitro effects of anti-CL/beta2-GPI and/or anti-PS/PT on the enhancement of platelet activation induced by stimulation with a low concentration of adenosine diphosphate (ADP). The purified IgG containing both anti-CL/beta2-GPI and anti-PS/PT caused significant enhancement of platelet activation caused by ADP. However, the purified IgG containing either anti-CL/beta2-GPI or anti-PS/PT had no enhancing effects on it. Furthermore, platelet activation was generated by the mixture of anti-CL/beta2-GPI-IgG and anti-PS/PT-IgG prepared from individual patients, but not by each fraction alone. These results indicate that anti-CL/beta2-GPI and anti-PS/PT may cooperate to promote platelet activation, which may contribute to the risk of cerebral infarction in patients with SLE.

Adolescent↗

Autoimmune aberration in sudden sensorineural hearing loss: association with anti-cardiolipin antibodies.

In view of the presence of autoantibodies against inner ear antigens, the pathogenesis of sudden deafness (SD) and progressive sensorineural hearing loss (PSNHL) is suggested to be of an autoimmune nature. However, microthrombosis of the inner ear may result from pathogenic anti-cardiolipin antibody (aCL) activity. We studied 30 patients (17 females and 13 males, age range 20-52 y), of whom 11 suffered from SD and 19 from PSNHL. All were clinically and serologically evaluated for association with autoimmune disorders (serological examination included: aCL, ANA, ENA, ANCA, proteinelectrophoresis, and complement levels). Twenty healthy matched subjects served as controls. None of the control group were aCL positive, whereas 8 out of 30 (27%) patients demonstrated low-moderate titers (P < 0.02), of whom 5 out of 8 suffered from SD. In addition, 2 aCL negative patients with PSNHL demonstrated hypergammaglubolinemia accompanied by hypocomplementemia, whereas none with SD had such abnormalities. Our data suggests that aCL is detected in patients with sudden sensorineural hearing loss and therefore may play an important role in the pathogenesis of this disability. If sustained by additional studies, these findings would warrant the consideration of anticoagulant therapy.

Adult↗

Anti-cardiolipin antibodies in sera from patients with periodontitis.

Antiphospholipid antibodies are commonly found in patients with systemic lupus erythematosus or the antiphospholipid syndrome, and a subset of such antibodies is associated with prothrombotic events such as stroke and with adverse pregnancy outcomes and fetal loss. We examined sera from 411 patients who were clinically characterized as to their periodontal disease status for serum levels of beta2-glycoprotein I-dependent anti-cardiolipin autoantibodies (anti-CL). The prevalence of patients with chronic periodontitis (CP) and generalized aggressive periodontitis (GAgP) positive for anti-CL (16.2% and 19.3%, respectively) was greater than that in healthy controls (NP) and localized aggressive periodontitis (LAgP) patients (6.8% and 3.2%). Patients with these autoantibodies demonstrated increased pocket depth and attachment loss compared with patients lacking the antibodies. Analysis of the data indicates that patients with generalized periodontitis have elevated levels of autoantibodies reactive with phospholipids. These antibodies could be involved in elevated risk for stroke, atherosclerosis, or pre-term birth in periodontitis patients.

Adult↗

Anti-cardiolipin antibodies (IgG and IgA) in women with recurrent fetal loss correlate to clinical and serological characteristics of SLE.

AIM OF STUDY: We investigated to which degree IgG, IgA and IgM anti-cardiolipin antibodies (aCL) are associated in recurrent abortion or late fetal death with other signs of autoimmune disease and in particular SLE. MATERIAL AND METHODS: Serological variables typical of SLE and of the anti-phospholipid antibody syndrome were measured once eight to 16 weeks after the last fetal loss in 158 women with recurrent abortion or late fetal death; women with manifest autoimmune rheumatic disease were excluded. RESULTS: (1) Positive values, i.e. above the 99th percentile of reference material, of IgG aCL and IgA aCL were observed in 4% and 7%, respectively, whereas 26% had positive values of IgM aCL. (2) IgG aCL and IgA aCL but not IgM aCL correlated to anti-nuclear antibodies and to anti-double stranded DNA. (3) Anti-double stranded DNA, IgG aCL and IgA aCL but not IgM aCL correlated to previous occurrence of thrombosis. (4) ANA correlated to lower blood platelet concentrations and higher erythrocyte sedimentation rates. CONCLUSIONS: Women with recurrent abortion or late fetal death who have higher but not necessarily abnormally high levels of IgG aCL or IgA aCL constitute a group with increased occurrence of clinical and serological characteristics of SLE. We suggest that these women be kept under surveillance for future development of autoimmune disease especially SLE. The women with high IgM aCL constitute another group without these characteristics.

Abortion, Habitual↗

Catastrophic anti-phospholipid syndrome in the absence of IgG anti-cardiolipin antibodies.

The Catastrophic Anti-phospholipid Syndrome (CAPS) is a rare acute clinical syndrome associated with serum anti-phospholipid antibodies (aPL). It is rarely preceded by a precipitating event. It may occur as a primary event or be associated with auto-immune diseases. We report a fatal case occurring post-endoscopic retrograde cholangio-pancreatography (ERCP) in a patient with Systemic Lupus Erythematosus (SLE), positive lupus anticoagulant and negative IgG with positive IgM anti-cardiolipin titres. The diagnostic and therapeutic difficulties of such cases is addressed.

Adult↗

Can tests for IgA, IgG, or IgM antibodies to cardiolipin or phosphatidylserine substitute for lupus anticoagulant assays in screening for antiphospholipid antibodies?

Antiphospholipid antibodies (APL) are detected by both ELISA and tests for lupus anticoagulants (LA). We evaluated ELISA tests for IgG, IgM, and IgA isotopes of antibodies binding cardiolipin (CL) and phosphatidylserine (PS) in samples from LA patients presenting with recurrent miscarriages. All values were expressed in multiples of the normal median (MOM). In 32% (11/34) of cases, not only were all ELISA values at or below 2.5 MOM, but the distribution of these ELISA MOM values within the normal range was similar to distribution of values from LA negative controls with the same history. Neither the use of PS as the antigen nor the addition of IgA assays improved the correlation of ELISA results with the presence of LA. ELISAs are inadequate as the sole screening test for these separate, but often associated, families of APL.

Abortion, Habitual↗

A large prospective survey of anti-cardiolipin antibodies in chronic hemodialysis patients.

We prospectively measured anti-cardiolipin antibody (ACLA) levels in 230 chronic hemodialysis (HD) patients over a 2-year period. Twenty-nine percent of HD-patients were found to have elevated IgG-ACLA titers. Males were more likely to have elevated IgG-ACLA titers. Elevated IgG-ACLA titers correlated with shortened AVG survival in HD-patients (mean of 156 vs. 238 days, p<0.05). There was no statistically significant correlation with access survival in AVF-patients. There seemed to be a higher mean IgG-ACLA titer in diabetics but they did not have statistically significant shorter angioaccess survival times. By logistic regression analysis, only IgG-ACLA positivity was predictive of premature angioaccess failure (p<0.05). In a selected subset of 16 patients with frequent angioaccess (AVG) failure and elevated IgG-ACLA levels, coumadin, titrated to an INR of 2 - 3, was found to produce a small (though statistically significant) prolongation of AVG survival.

Adolescent↗

Antibodies to beta 2-glycoprotein I and cardiolipin with symptoms suggestive of systemic lupus erythematosus in parvovirus B19 infection.

Parvovirus B 19 infection may mimic systemic lupus erythematosus (SLE) in its clinical presentation. Serological abnormalities during acute infection have been reported, including positive antinuclear antibodies and anti-doublestranded DNA antibodies. We describe a patient who, in addition to the clinical and laboratory findings suggestive of SLE, was found to have antibodies to cardiolipin and beta2 glycoprotein I. The symptoms resolved and the antibodies disappeared over a 9 month period. This report highlights the striking similarity between SLE and parvovirus B19 infection and the potential difficulty in distinguishing between the diseases.

Adult↗

[The prediction of thrombosis development in patients with systemic lupus erythematosus: the role of antibodies to cardiolipin].

In patients with systemic lupus erythematosus (SLE), the synthesis of antibodies to cardiolipin (A-CL) is associated with the development of venous and arterial thromboses localized in minor and middle-sized vessels, in the venous system and capillaries. The determination of various A-CL isotypes may be used to predict thromboses in SLE patients. Overall 210 patients (185 women and 25 men) with a verified diagnosis of SLE were examined. The patients were not screened in accordance with some or other clinical signs of the antiphospholipid syndrome. The control group comprised 100 healthy subjects (donors). The IgG, IgA and IgM isotypes of A-CL were determined by ELISA. Sera of SLE patients showed an increase of the concentration of A-CL of both certain isotypes and their potential combinations. Among A-CL-positive patients, the IgG isotype of A-CL was detected in 75% of cases, the IgM isotype of A-CL in 61%, and the IgA isotype of A-CL in 36% of cases. Thrombotic complications were recorded in 19% of patients. They were induced by hyperproduction of the three combinations of the A-CL isotypes: A-CL IgM, IgM+IgA, and IgG+IgA+IgM. Patients whose sera contained A-CL of all three types at a time were most prone to thrombotic complications. It has turned out that the percentage of SLE patients with thromboses was higher than that of SLE patients without thromboses, starting from the definite A-CL concentration (21 GPL).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Antibodies to beta2-glycoprotein I and antibodies to cardiolipin in antiphospholipid syndrome: analysis of sensitivity and specificity].

To study sensitivity and specificity of antibodies to beta 2-glycoprotein I (B2GP-I) and antibodies to cardiolipin (CL) in diagnosis of antiphospholipid syndrome (APS), we examined 19 patients with primary antiphospholid syndrome (PAPS), 23 patients with secondary APS (SAPS) and systemic lupus erythematosus (SLE) and 73 patients with SLE. Antibodies to B2GP-I and CL of IgG isotype were measured at enzyme immunoassay. The levels of IgG aCL and IgG aB2GP-I in the serum of PAPS patients were 69.9 +/- 116.0 GPL, 74.1 +/- 117.4 SGU, respectively; of SAPS and SLE patients 60.5 +/- 68.9 GPL and 66.2 +/- 88.3 SGU, respectively. These values were significantly higher than in SLE patients (19.5 +/- 27.6 GPL, p = 0.0025 and p = 0.0012; 14.5 +/- 41.9 SGU, p = 0.0001, respectively) and donors (3.9 +/- 3.8 GPL, p = 0.0001; 5.7 +/- 1.2 SGU, p = 0.001). By IgG aCL and IgG-aB2GP-I, PAPS and SAPS patients differed insignificantly (p > 0.05), but these values correlated positively (r = 0.85; p < 0.0005 for PAPS and r = 0.9, p < 0.005 for SAPS). Simultaneous detection of IgG aCL and IgG aB2GP-I occurred in 36.8% in PAPS, 52.4% in SAPS and 12.3% in SLE. 10.5% PAPS patients were positive by IgG aCL as well as 9.5% with SAPS and 13.4% with SLE. Isolated rise of IgG aB2GP-I concentration was observed in 21.1% patients with PAPS, in 9.5% patients with SAPS and 9.6% patients with SLE. Of 43 patients with a history of thrombosis, 46.5% were positive by IgG aCL and IgG aB2GP-I, 7.0% positive only by IgG aCL and 11.6% only by IgG aB2GP-I. Levels of IgG aCL and IgG aB2GP-I in patients with thrombosis (64.7 +/- 87.5 GPL and 66.0 +/- 94.8 SGU, respectively) were significantly higher than in patients without them (19.6 +/- 3.8 GPL, p = 0.009 and 16.4 +/- 52.2 SGU, p = 0.0001). In venous thrombosis IgG aCL and IgG aB2GP-I were higher than in arterial thrombosis (p < 0.004). For diagnosis of APS sensitivity and specificity of IgG aB2GP-I and IgG aCL were 60.0 and 83.8%; 57.1 and 73.5% (p > 0.05), respectively. As to thrombosis, the sensitivity and specificity were 58.1 and 84.6%; 54.5 and 72.7% (p > 0.005), respectively. Thus, IgG aB2GP-I is an essential additional marker of APS. In the presence of APS symptoms, but in negative results of APS test it is justified to confirm APS diagnosis by aB2GP-I test results. To make APS diagnosis more accurate, it is valid to make simultaneous measurements of aCL using standard B2GP-I dependent enzyme immunoassay and aB2GP-I.

Adult↗

Study of anti-cardiolipin and anti-beta2-glycoprotein I antibodies in patients with ischemic stroke.

The study of IgG and IgM anti-cardiolipin antibodies (IgG/IgM aCL) is now well accepted and is routinely used in the risk assessment of various conditions associated with thrombosis. The aim of the study was to define whether the investigation of aCL is sufficient by itself to evaluate a risk of ischemic stroke. Frequency of aCL and anti-beta2-glycoprotein I (beta2-GPI) antibodies was prospectively investigated in 96 patients with ischemic stroke and in 119 controls by ELISA. In ischemic stroke patients IgG aCL were found in 36%, the IgM-aCL were found in 58%, the IgG-IgM-aCL were found in 43%. The levels of both antibodies were higher in patients with ischemic stroke than in controls (p < 0.01). In controls, IgM-aCL were positive in 2% and IgG-aCL antibodies were negative. IgG-beta-GPI Abs were found in ischemic patients in 19% and IgM-beta2-GPI Abs in 37%. The IgG-IgM-anti-beta2-GPI Abs were found in 24% patients. They were negative in controls. There was a correlation between levels of aCL and anti-beta2-GPI Abs for both isotypes (r = 0.728) but not between IgG- and IgM-beta2-GPI Abs. IgG-aCL test was more sensitive for ischemic stroke than the IgG-beta2-GPI Abs test (71.4%, respectively 65.7%) but less specific (66.8%, respectively 88.6%). The sensitivity of anti-beta2-GPI Abs for ischemic stroke was increased when both isotypes were tested. These results showed that aCL and anti-beta2-GPI Abs could be pathogenetically important for ischemic stroke and that anti-beta2-GPI Abs testing might contribute to a better evaluation of ischemic stroke.

Aged↗

IgG anti-cardiolipin antibodies-markers of inflammation in diabetic patients with ischemic stroke.

Some researchers investigated the role of anticardiolipin antibodies in the pathogenesis of the ischemic stroke. The objective of the study was to evaluate the relationship between the prevalence of the IgG anti-cardiolipin antibodies (IgG aCL) and ischemic stroke in patients with diabetes mellitus. IgG aCL were prospectively investigated in 87 diabetic patients with ischemic stroke (mean age 78.5 years) and in 68 diabetic patients without ischemic stroke (mean age 72.8 years). IgG aCL were determined by ELISA. Twenty-three out of 87 diabetic patients without ischemic stroke had IgG aCL and 25 out of 68 diabetic patients without stroke had IgG aCL. The IgG aCL titer did not differ significantly between patients with ischemic stroke and those without stroke (p>0.05). Our data showed that IgG aCL are not a risk factor for ischemic stroke in diabetic patients. Both patients with diabetes and those with diabetes and ischemic stroke had serum IgG aCL. IgG aCL indicate inflammatory conditions in these pathologies.

Aged↗

Crossreactivity of anti-cardiolipin antibodies with glycolipids and endothelial cells.

To investigate the crossreactivity of anti-cardiolipin antibodies (aCL) with glycolipids and endothelial cells, we used (1) culture supernatants derived from Epstein-Barr virus (EBV)-transformed peripheral lymphocytes of patients with systemic lupus erythematosus (SLE) complicated by antiphospholipid syndrome, and also (2) sera from patients with SLE. The results obtained from culture supernatants demonstrated that aCL crossreacts with myelin-derived acidic glycolipid sulfatide, bacterial endotoxin glycolipid lipid A and human umbilical vein endothelial cells (HUVEC). The results obtained from sera showed a significant correlation between levels of aCL and anti-sulfatide antibody, and between levels of aCL and anti-HUVEC antibody. These findings indicate that aCL can bind to the myelin sheath and HUVEC, which may have implications for the pathogenic potential of aCL for nervous system involvement and thrombotic complications.

Antibodies, Anticardiolipin↗

Measurement of anti-endothelial and anti-cardiolipin autoantibodies and intercellular adhesion molecules-1 in patients with systemic and cutaneous vasculitis.

Two types of autoantibodies and intercellular adhesion molecule-1 (ICAM-1) were measured in patients with vasculitis. There were 13 patients with systemic vasculitis, and 12 with cutaneous vasculitis. The measured antibodies included antiendothelial cell antibodies (AECA) and anti-cardiolipin (ACL) antibodies of three isotypes. Results showed that patients with systemic vasculitis had elevated levels of ICAM-1 and IgG isotype ACL antibodies. Higher levels of ICAM-1 and IgG isotype ACL antibody were found in patients with systemic vasculitis than in those with cutaneous vasculitis. Levels of ICAM-1 and IgG isotype ACL antibodies also decreased after disease activity subsided in patients with systemic vasculitis. Measurement of ICAM-1 and autoantibodies may be useful in evaluating the extent of involvement, and for following the disease course.

Adolescent↗

Sneddon's syndrome, anti-cardiolipin antibody and glomerular thrombosis.

Sneddon's syndrome, cerebrovascular thrombosis and livedo reticularis, is often a variant of the "primary" anti-phospholipid syndrome (PAPS). We report a woman with PAPS, presenting as Sneddon's syndrome, with renal impairment and glomerular thrombosis on renal biopsy. An IgG anti-cardiolipin antibody (aCL) was identified. The aCL was purified by affinity chromatography, gel filtration chromatography and ion-exchange chromatography, assayed in a modified ELISA and found to be of the type that requires the plasma protein beta 2-GPI to bind aCL. As beta 2-GPI has anticoagulant properties it is postulated that its interaction with aCL has a pathogenic role in the thrombotic lesions associated with aCL.

Adult↗

Cardiolipin antibodies and lupus anticoagulant in young patients with a cerebrovascular accident in the past.

To determine whether young patients who suffered a stroke in the past, have a higher prevalence of ACA of LAC as compared to healthy controls, we evaluated 44 stroke patients and 46 controls in a case-control study for the presence of ACA and LAC. All the patients had had a stroke under the age of 50 yr and the stroke date was less than 5 yr ago (mean 2.5 yr). Stroke was defined as an ischaemic cerebral infarction and was confirmed by angiography, CT-scan or MRI. An age- and sex-matched group of healthy volunteers served as controls. The mean age of the patients was 41.4 yr (range 22-52 yr), and of the controls 36.8 yr (range 24-50 yr). Serum and plasma from both groups was examined for IgM- and IgG-ACA and LAC. One patient was positive for both IgG- and IgM-ACA, whereas 3 controls were found positive for IgG-ACA. For 2 patients and 5 controls an equivocal result was obtained for IgG-ACA or IgM-ACA. None of the patients or controls were positive for LAC. The differences between the patient and control group were statistically not significant. In conclusion, no difference was found in the prevalence of cardiolipin antibodies in sera from patients with a stroke within the last 5 yr and an age- and sex-matched control group. There was no correlation either between the presence of lupus anticoagulant and the occurrence of a stroke in the past.

Adult↗

[Connections between ischemic heart disease and anti-cardiolipin antibody positivity].

IgG and IgM anti-cardiolipin antibodies (aCL) were measured in 60 patients with ischaemic heart disease by an immunoenzymatic assay. aCL levels higher than normal were detected in 12 of 40 patients (30%) with acute myocardial infarction (AMI) and in 7 of 20 patients (35%) with angina pectoris (AP). These values were significantly higher (p < 0.05) than those detected in the control group (3/40; 7.5%). As regards the clinical picture, the complications and the outcome of the disease, no difference was observed between aCL-positive and negative patients with AMI. 9 of 12 aCL-positive patients with AMI showed increased levels of aCL in a blood sample obtained in day 1 after admission. Therefore, we must admit such positivity as preexistent to the myocardial infarction. These data together with the high prevalence of aCL in patients with AP suggest that an association should exist between raised levels of aCL and increased risk for AMI in patients with coronary artery disease.

Aged↗

[Distribution of cofactor-dependent anti-cardiolipin antibodies in collagen diseases].

Cofactor-dependent IgG anti-cardiolipin antibodies (ACA) were examined in sera from various connective tissue diseases by ELISA using purified human beta 2-glycoprotein I. The frequency and titer of cofactor-dependent IgG ACA were higher in patients with SLE than in those with other diseases, such as RA, SSc, PM/DM, overlap syndrome, and MCTD. The predictive value for SLE was 95%. However, all of the ACA were not cofactor-dependent in SLE patients. These results indicated that cofactor-dependent IgG ACA were specific for SLE patients, but the epitopes of ACA were heterogenous, depending on various clinical manifestations.

Antibodies, Anticardiolipin↗