Antibodies against phospholipids and oxidized LDL in alcoholic patients.
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Antiphospholipid antibodies (APA) are a generic term describing antibodies that recognize various phospholipids. Hepatocyte damage is a cardinal event in the course of alcoholic liver injury and autoantibodies against phospholipids could play an important role in this process. APA in alcoholic patients seem to reflect membrane lesions, impairment of immunological reactivity, liver disease progression and they correlate significantly with disease severity. LDL oxidation is supposed to be one of the most important pathogenic mechanisms of atherosclerosis and antibodies against oxidized low-density lipoprotein (oxLDL) are some kind of an epiphenomenon of this process. The scope of our study was to determine some autoantibodies (IgG-oxLDL and antiphospholipid antibodies) and their possible changes in alcoholic patients. We studied IgG-oxLDL and four APA - anticardiolipin antibodies (ACA), antiphosphatidylserine antibodies (APSA) antiphosphatidylethanolamine antibodies (APE) and antiphosphatidylcholine antibodies (APCA) in 35 alcoholic patients with mildly affected liver function at the beginning of the abuse treatment. The control group consisted of 60 healthy blood donors. In the studied group, we obtained positive results concerning total ACA in 17.1 % of alcoholic patients (8.3 % in the control group), 11.4 % IgG-ACA (6.7 %), 8.6 % IgM-ACA (3.3 %), 14.3 % total APE (6.7 %), 14.3 % total APCA (8.3 %) and 20 % total APSA (8.3 % in the control group). The IgG-oxLDL (406.4+/-52.5 vs 499.9+/-52.5 mU/ml) was not affected in alcoholic patients. We conclude that the autoantibodies against oxLDL are present in sera of alcoholics and healthy blood donors. Based on our results which revealed a wide range of IgG-oxLDL titres in the healthy population, this parameter does not appear to be very promising for the evaluation of the risk of atherosclerosis. Alcoholics with only mild affection of liver functions did not exhibit a significantly higher prevalence of all studied antiphospholipid antibodies (ACA, APSA, APE, APCA) which could lead to membrane lesions in these patients. (+info)
Cerebral vasculopathy in HIV infection revealed by transcranial Doppler: A pilot study.
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BACKGROUND AND PURPOSE: There is growing evidence for affection of cerebral vessels during human immunodeficiency virus (HIV) infection. We prospectively evaluated cerebrovascular reserve capacity (CRC) in HIV-seropositive patients by transcranial Doppler sonography (TCD) after systemic administration of acetazolamide. We hypothesized that a disturbed vasoreactivity would reflect the cerebral arteries' involvement in HIV infection. METHODS: We assessed the mean blood flow velocity (BFV) of the middle cerebral artery and its increase after intravenous administration of 1 g acetazolamide (CRC) in 31 HIV-infected individuals without symptoms of cerebrovascular disease (mean+/-SD age, 39+/-11 years). Stenotic or occlusive lesions of the large brain-supplying arteries were excluded by color-coded duplex and transcranial imaging. BFV and CRC were also measured in an age-matched group of 10 healthy control subjects. Patients were classified according to clinical, laboratory, and neurophysiological parameters. We also performed cerebral MRI (n=25) and rheumatological blood tests (n=26). RESULTS: Baseline BFV and CRC both were significantly reduced in HIV-infected patients as compared with control subjects (P<0.05, Student's t test). These findings did not correlate with duration of seropositivity, helper cell count, or other clinical, rheumatological, and neuroradiological findings. CONCLUSIONS: Our findings support the hypothesis of a cerebral vasculopathy etiologically associated with HIV infection. (+info)
Anti-phospholipid antibodies and CD5+ B cells in HIV infection.
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This cross-sectional study evaluates the correlation between anti-phospholipid antibodies and CD5+ B cells in 110 patients infected with HIV-1. There were 89.1% of the patients who had IgG antibodies against cardiolipin and phosphatidylserine. The prevalence of IgM and IgA antibodies was < 22%. AIDS was associated with lower frequencies of IgM antibodies against cardiolipin (P = 0.05) and IgG-antibodies against cardiolipin and phosphatidylserine (P = 0.011). Drug users had higher IgM antibodies against phospholipids than patients from other risk groups (P = 0.02). A history of thromboembolic events was not accompanied by higher levels of anti-phospholipid antibodies (P > 0.2). No correlation between anti-phospholipid antibodies and CD5+ B cells was detected. Percentage part of CD5+ B lymphocytes was elevated in all patients and absolute CD4+ T lymphocyte counts and HIV p24 antigen were inversely correlated. In advanced disease a significant reduction of anti-phospholipid antibodies was contrasted with persistent elevation of CD5+ B lymphocytes. These observations may reflect immunological dysfunction involving apoptosis and endothelial damage rather than polyclonal B cell hyperstimulation. A possible explanation would be that in HIV infection an increased rate of spontaneous apoptosis in peripheral blood lymphocytes is accompanied by functional and structural changes of mitochondria. Therefore, structurally altered mitochondrial phospholipids could serve as antigen to induce specific humoral immune responses. (+info)
Antibodies to adult human endothelial cells cross-react with oxidized low-density lipoprotein and beta 2-glycoprotein I (beta 2-GPI) in systemic lupus erythematosus.
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Cardiovascular manifestations are common in systemic lupus erythematosus (SLE). Oxidized low-density lipoprotein (oxLDL) is implicated in cardiovascular disease, especially atherosclerosis, and cross-reacts with antibodies to cardiolipin (aCL). beta 2-GPI is a plasma protein participating in the coagulating cascade, and is also cofactor for aCL, and some aCL have been shown to be directed against beta 2-GPI and/or complexes between beta 2-GPI and phospholipids. Lysophosphatidylcholine (LPC) is a phospholipid present both in oxLDL and in damaged endothelium, and we recently showed that LPC is involved in the antigenicity of oxLDL. Antibodies to endothelial cells (aEC) correlate with diseases activity in SLE and vasculitis, and we recently showed that aEC are enhanced in cardiovascular disease such as borderline hypertension and early atherosclerosis. aEC were determined using EC from adult V. Saphena Magna. Antibody levels were determined by ELISA. aEC of IgG type were enhanced in 184 patients with SLE compared with 85 healthy controls. There was a close correlation between aoxLDL, aCL, aLPC, a beta 2-GPI and aEC. Binding of sera to EC was competitively inhibited by beta 2-GPI, LPC and oxLDL. Taken together, the data indicate that EC share antigenic epitopes with beta 2-GPI and with oxLDL, especially LPC. Phospholipids in EC membranes may thus be antigenic epitopes. beta 2-GPI may bind to these phospholipids, and become an autoantigen. LPC is formed by oxidation of phospholipids and/or proinflammatory factors leading to activation of phospholipase A2, and the findings indicate the potential role of both lipid oxidation and phospholipase A2 in SLE. (+info)
Conformationally altered beta 2-glycoprotein I is the antigen for anti-cardiolipin autoantibodies.
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Anti-cardiolipin autoantibodies (aCL) induce thrombosis and recurrent fetal death. These antibodies require a 'cofactor', identified as beta 2-glycoprotein I (beta 2-GPI), to bind phospholipids. We show here that aCL can bind beta 2-GPI in the absence of phospholipid. Binding of aCL to beta 2-GPI is dependent upon the beta 2-GPI being immobilized on an appropriate surface including cardiolipin, irradiated polystyrene and nitrocellulose membrane. This effect cannot be explained by increased antigen density of beta 2-GPI immobilized on these surfaces. Rather, conformational changes that occur following the interaction of beta 2-GPI with phospholipid render this protein antigenic to aCL. Liquid-phase beta 2-GPI was not antigenic for aCL. Thus, aCL cannot bind circulating beta 2-GPI. These findings may explain why patients with aCL can remain healthy for many years but then undergo episodes of thrombosis or fetal loss without changes in their circulating aCL profile, as the triggering event for these pathologies can be predicted to be one that renders beta 2-GPI antigenic for aCL. (+info)
A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus.
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OBJECTIVE: To prospectively analyze the association between changes in cognitive function and circulating anticardiolipin antibodies (aCL) over a period of 5 years in patients with systemic lupus erythematosus (SLE). METHODS: Cognitive function was assessed in 51 unselected female SLE patients at baseline and after a mean followup of 64.5 months (range 52-71 months), using standardized tests of cognitive function, i.e., the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised, and the California Verbal Learning Test. Circulating IgG, IgA, and IgM aCL and anti-double-stranded DNA (anti-dsDNA) antibody levels were determined by enzyme-linked immunosorbent assay on 4-7 occasions over the same time period. Persistent antibody reactivity was defined as levels more than 2 standard deviations (moderately positive) and more than 5 standard deviations (highly positive) above the mean for normal controls over the duration of the study. Changes in overall cognitive performance and in raw scores on individual cognitive tests were compared in patients who were persistently positive or negative for aCL. RESULTS: At baseline 11 patients (22%) were cognitively impaired, compared with 7 (14%) at followup. Between 16% and 37% of patients had persistently elevated aCL levels of different isotypes. There was no significant difference in the prevalence of overall cognitive impairment in patients who were persistently positive for aCL compared with those who were not. In contrast, over the period of study, patients who had persistent IgG aCL positivity had a reduction in psychomotor speed, and patients who had persistent IgA aCL positivity had a reduction in conceptual reasoning and executive ability. Similar associations with anti-dsDNA antibodies were not found. CONCLUSION: These results suggest that IgG and IgA aCL may be responsible for long-term subtle deterioration in cognitive function in patients with SLE. (+info)
A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus.
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OBJECTIVE: To determine the relationship between persistently raised anticardiolipin antibody (aCL) levels and neuropsychological performance in patients with systemic lupus erythematosus (SLE). METHODS: Forty-five patients with SLE underwent a detailed neuropsychological assessment on 2 occasions 12-18 months apart. Serum samples stored since the time of previous assessments as well as samples obtained 6 months to 2 years before the first neuropsychological assessment were tested for IgG aCL levels. Patients were divided into 4 groups according to the number of times their aCL levels were elevated (never, once, twice, 3 times). A wide-ranging battery of new neuropsychological tests was utilized, and the results were compared with double-stranded DNA (dsDNA) antibody levels, C3 levels, and results of magnetic resonance imaging (MRI). RESULTS: Analysis of variance revealed that the group with persistently elevated aCL levels performed less well than the other groups. At the first neuropsychological assessment, poorer performance by this group was noted for letter cancellation (P = 0.02), trail making task B (P = 0.04), and digit span (P = 0.03). At the second assessment, letter cancellation (P = 0.01), trail making task A (P = 0.03), trail making task B (P = 0.01), word fluency (P = 0.01), and reaction time (P = 0.05) were impaired. In contrast, no significant differences in neuropsychological test results were identified with respect to DNA antibody or C3 levels. MRI abnormalities were associated with both persistent elevation of aCL levels and low C3 levels. CONCLUSION: Levels of IgG aCL that were persistently elevated over a 2-3-year period (as opposed to never or occasionally elevated) were associated with significantly poorer performance in cognitive function by patients with SLE. Tasks requiring speed of attention and concentration appear to be particularly affected. (+info)
A possible role for activated protein C resistance in patients with first and second trimester pregnancy failure.
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Thrombophilia was recently suggested as a possible factor in recurrent pregnancy losses. We studied prospectively 125 patients (mean age 31.4 +/- 5.6 years) with one or more first or second trimester pregnancy losses for the prevalence of activated protein C resistance (APCR). Proteins C and S antigens, antithrombin III, anticardiolipin, and lupus anti-coagulant were also evaluated. Patients with uterine malformations, hormonal abnormalities, chromosomal translocations and infectious causes were excluded. A control group of 125 women with no past fetal loss were matched with the study group. Whenever the APC-sensitivity ratio (APC-SR) was +info)