Biomedical subjects

Anna Horváth

Publications and source records attributed to Anna Horváth.

8 recordsLinked to original sources

PubMed2006

Novel anti-cholesterol monoclonal immunoglobulin G antibodies as probes and potential modulators of membrane raft-dependent immune functions.

Natural autoantibodies against cholesterol are present in the sera of all healthy individuals; their function, production, and regulation, however, are still unclear. Here, we managed to produce two monoclonal anti-cholesterol antibodies (ACHAs) by immunizing mice with cholesterol-rich liposomes. The new ACHAs were specific to cholesterol and to some structurally closely related 3beta-hydroxyl sterols, and they reacted with human lipoproteins VLDL, LDL, and HDL. They bound, usually with low avidity, to live human or murine lymphocyte and monocyte-macrophage cell lines, which was enhanced substantially by a moderate papain digestion of the cell surface, removing some protruding extracellular protein domains. Cell-bound ACHAs strongly colocalized with markers of cholesterol-rich lipid rafts and caveolae at the cell surface and intracellularly with markers of the endoplasmic reticulum and Golgi complex. These data suggest that these IgG ACHAs may serve as probes of clustered cholesterol (e.g., different lipid rafts) in live cells and thus may also have immunomodulatory potential.

Antibodies, Monoclonal↗

PubMed2005

Dramatic changes in the serum levels of anti-cholesterol antibodies after eversion endarterectomy in patients with severe carotid atherosclerosis.

Our goal was to study changes in anti-cholesterol antibodies (ACHA) levels in patients with severe carotid stenosis after eversion endarterectomy. Seventy consecutive patients who underwent eversion endarterectomy at the Department of Cardiovascular Surgery, Semmelweis University, Budapest, were included in the study. Serum samples from 66 healthy volunteers served as controls. Patients had medical check up at 5.7 (4.6-8.0) weeks (median (interquartile range)), 6.8 (6.2-7.9) months as well as 13.8 (12.3-19.0) months after endarterectomy. In all patients the carotid arteries were investigated by color duplex ultrasound. ACHA concentrations were determined in the serum samples taken before operation as well as at the first and last follow-up visits by using an ELISA method. ACHA concentrations (median (interquartile range) were found to be significantly (p<0.0001) lower in the sera of the patients with carotid atherosclerosis (13.5 (8.4-21.3)AU/ml) than in the healthy subjects (26.1 (20.9-33.2)AU/ml) (Mann-Whitney test). Strong negative correlation was found between the preoperative ACHA and LDL-cholesterol levels (r=-0.413, p=0.0004). Serum ACHA concentrations significantly (p<0.0001) increased from the values measured before operation (13.5 (8.4-21.3)AU/ml) to 27.1 (19.9-34.7)AU/ml measured at the end of the 14 months long follow-up. Increase occurred only in patients with low or medium baseline ACHA concentration. Our present findings indicate that after surgical removal of atherosclerotic plaques from the carotid arteries the reduced baseline levels of ACHA reach normal values in 1 year. Different not mutually exclusive mechanisms (binding of ACHA to lipid/lipoproteins particles, to advanced plaques or reversibly injured endothelial cells in CNS) can be responsible for this novel finding.

Acute-Phase Proteins↗

PubMed2003

Significant decrease of the enhancement/neutralization index in HIV patients during highly active antiretroviral therapy (HAART).

Authors studied the effect of highly active antiretroviral therapy (HAART) on balance of the antibodies that enhance or neutralize growth of HIV-1(IIIB) strain in MT-4 cells in the presence or absence of human complement. Sequential serum samples were collected from 28 patients in advanced stage of HIV disease before and during HAART. The balance of the enhancing and neutralizing antibodies was expressed by an index value (E/N I). Samples with an E/N I of <0.5 (twofold decrease in virus production) were considered as neutralizing, whereas samples with an E/N I>2.0 (twofold increase in virus production) were considered as enhancing. At the beginning of HAART serum samples from eight patients enhanced, and samples from only two patients neutralized the virus in the presence of complement, median (25th-75th percentile) value of E/N I was 1.32 (0.79-2.29). E/N I significantly (P<0.0001) dropped to 0.37 (0.19-0.57) during the follow-up period of 18.5 (10.5-23.5) months under HAART. Similar changes were detected when serum samples were tested with no complement added. The E/N I values were also markedly decreased when cultures inoculated with mixtures of HIV and purified IgG prepared from serum pools taken before and during HAART, respectively, were compared. In the last samples of 20/28 patients, neutralization was measured even in the presence of complement while enhancement was found with none of these samples. These findings suggest that HAART results in disappearance of enhancing antibodies and switches the E/N I toward neutralization.

Antibodies, Blocking↗

PubMed2003

Anti-cholesterol antibodies in human sera.

In the last 30 years many research showed that high serum cholesterol level is a great risk for the atherosclerosis. In recent years, it has become clear that the immune system has a major role in atherosclerosis development and progression, and has binding capacity to cholesterol as well. It has been demonstrated in animal experiments, that anti-cholesterol antibodies (ACHA) can prevent cholesterol diet induced atherosclerosis. Our group is looking for the answer, whether ACHA have the same function in animals and in humans, or not. In this review we summarize our studies in human sera. We measured serum ACHA levels in different groups of patients with atherosclerotic diseases in patients with viral infections and in healthy population. In the summary we write about the possible functions of ACHA in the human immune system.

Animals↗

PubMed2003

Serum anti-cholesterol antibodies in chronic hepatitis-C patients during IFN-alpha-2b treatment.

Previously we detected more than 3 times higher anti-cholesterol antibody (ACHA) levels in HIV positive patients compared to healthy individuals, however, this level significantly decreased during highly active anti-retroviral therapy (HAART). In our present study we examined whether these findings could also be detected in patients with chronic hepatitis C (CHC). We calculated the correlation between the ACHA levels and the C5b-9 complement activation product. 39 patients with CHC were treated with IFN-alpha-2b (Schering-Plough) 5 MU daily for 6 weeks, followed by 5 MU TIW. Serum levels of ACHA and complement activation products were measured with ELISA. Serum HCV RNA was measured by a highly sensitive branched DNA technique before and 3, 6 and 12 months after the beginning of IFN-alpha-2b therapy. 52 healthy persons served as controls. At the onset of treatment ACHA level was significantly (p = 0.0062) higher in patients (40 (24-69) AU/ml) (median (interquartile range)) than in control sera (26 (20-35) AU/ml). In the 26 responder patients ACHA levels decreased to the normal level during the therapy, but no change was observed in the 13 non-responders. In patients with a sustained response ACHA levels remained low till the end of the 12 months IFN treatment. ACHA levels were significantly (p = 0.0422) higher in the patients with low (< 4.0 mmol/l) than in those with normal (> or = 4.0 mmol/l) cholesterol concentrations. The ACHA level before the therapy strongly correlated (r = 0.5499, p = 0.0014) with C5b-9 serum levels. ACHA levels are elevated in CHC, but this elevation is not as high as in HIV. Decrease of viral load by IFN-alpha-2b treatment in the responders results in normalization of ACHA concentration. High ACHA levels in patients with low serum cholesterol concentration suggest that high ACHA levels may contribute to the decrease in cholesterol levels. The correlation between the ACHA and C5b-9 levels indicate, that the ACHA may play a role in the complement activation in CHC.

Adult↗

PubMed2002

Relationship of anti-60 kDa heat shock protein and anti-cholesterol antibodies to cardiovascular events.

BACKGROUND: Several recent studies have indicated an association between key inflammatory mediators and atherosclerotic diseases. We evaluated whether high levels of antibodies against heat shock proteins and cholesterol (ACHA) predicted cardiovascular (CV) events. METHODS AND RESULTS: We used blood samples from the Heart Outcomes Prevention Evaluation (HOPE) study to conduct a nested case-control study of 386 cases with CV events and 386 age- and sex-matched HOPE study controls without events. We explored the relationship between anti-hsp antibodies, ACHA, and subsequent outcomes (incident myocardial infarction, stroke, or CV death) during a mean follow-up of 4.5 years using conditional logistic regression. High levels of anti-hsp65 antibodies (> or =90th percentile) predicted CV events (OR, 2.1; 95% CI, 1.2 to 3.9, P=0.01). Anti-hsp60 antibodies did not predict any event type, whereas incident stroke developed significantly less frequently in patients with high ACHA levels. Anti-hsp antibodies and ACHA did not correlate with inflammatory (fibrinogen, C-reactive protein, interleukin-6, intracellular adhesion molecule-1) or infectious markers (C pneumoniae or cytomegalovirus antibodies). Anti-hsp65 antibodies (> or =90th percentile) and fibrinogen (highest tertile) had a strong joint effect: patients with high concentrations of both had more CV events (OR, 5.5; 95% CI, 1.8 to 17.5, P=0.004) than patients with low levels of both. A similar joint effect (OR, 2.7; 95% CI, 1.3 to 5.7, P=0.01) was found for high levels of anti-hsp65 and presence of cytomegalovirus antibodies. CONCLUSIONS: Serum antibodies to hsp65 were associated with subsequent CV events in this study of high-risk patients, independent of conventional cardiovascular risk factors and other inflammatory markers.

Aged↗

PubMed2002

IL-6 and lipoprotein(a) [LP(a)] concentrations are related only in patients with high APO(a) isoforms in monoclonal gammopathy.

We have investigated the influence of apo(a) genetics on the relationship between interleukin (IL)-6, and lipoprotein (a) [Lp(a)] levels in 154 patients with monoclonal gammopathy and 189 healthy subjects. No significant differences in Lp(a) levels and distribution of subjects with different sizes of apo(a) isoforms were found between patients and healthy controls. Relationship between IL-6 and Lp(a) levels was strongly dependent on the size of apo(a) isoforms. In patients with high-size apo(a) isoforms Lp(a) levels positively correlated (r=0.475, P=0.0007) to IL-6 concentrations, whereas no correlation was found in patients with low apo(a) isoforms. Our present finding may provide a plausible explanation for the contradictory findings about the acute phase protein nature of Lp(a).

Adult↗

PubMed2002

Helicobacter pylori infection in connective tissue disorders is associated with high levels of antibodies to mycobacterial hsp65 but not to human hsp60.

BACKGROUND: To investigate whether the Helicobacter pylori status influences levels of antibodies against mycobacterial heat shock protein (hsp) 65 and human hsp60 in systemic autoimmune diseases and to study the concentration of anti-H. pylori antibodies in autoimmune patients and healthy controls. MATERIALS AND METHODS: Antibodies against human heat-shock protein hsp60, mycobacterial heat-shock protein hsp65 were analyzed by ELISA. Anti-Helicobacter antibodies were determined by enzyme immunoassay. RESULTS: There was a markedly higher prevalence of H. pylori infection in undifferentiated connective tissue disease (82%) (n = 33) and systemic sclerosis (78%) (n = 55) but not in systemic lupus erythematosus (n = 49), polymyositis/dermatomyositis (n = 14), rheumatoid arthritis (n = 21) or primary Raynaud's syndrome (n = 26) compared with controls (59%) (n = 349). In autoimmune diseases H. pylori infection was associated with elevated levels of antihsp65 (p =.008) but not of antihsp60. Anti-hsp65 levels were significantly higher in H. pylori-infected (n = 129) than in uninfected patients (n = 69) (p =.0007). CONCLUSIONS: These findings indicate that in autoimmune diseases the infection with the H. pylori bacterium is associated with increased concentration of antimycobacterial hsp65.

Adult↗