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Biomedical subjects

E Matsuura

Publications and source records attributed to E Matsuura.

At least 19 recordsLinked to original sources
PubMed2006

Antibodies against beta2-glycoprotein I complexed with an oxidised lipoprotein relate to intima thickening of carotid arteries in primary antiphospholipid syndrome.

To explore whether antibodies against beta2-glycoprotein I (beta2GPI) complexed to 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and to oxidised low-density lipoproteins (oxLDL) relate to paraoxonase activity (PONa) and/or intima media thickness (IMT) of carotid arteries in primary antiphospholipid syndrome (PAPS). As many as 29 thrombotic patients with PAPS, 10 subjects with idiopathic antiphospholipid antibodies (aPL) without thrombosis, 17 thrombotic patients with inherited thrombophilia and 23 healthy controls were investigated. The following were measured in all participants: beta2GPI-oxLDL complexes, IgG anti-beta2GPI-oxLig-1, IgG anti-beta2GPI-oxLDL antibodies (ELISA), PONa, (para-nitrophenol method), IMT of common carotid (CC) artery, carotid bifurcation (B), internal carotid (IC) by high resolution sonography. Beta2GPI-oxLDL complex was highest in the control group (p < 0.01), whereas, IgG anti-beta2GPI-oxLig1 and IgG anti-beta2GPI-oxLDL were highest in PAPS (p < 0.0001). In healthy controls, beta2GPI-oxLDL complexes positively correlated to IMT of the IC (p = 0.007) and negatively to PONa after correction for age (p < 0.03). PONa inversely correlated with age (p = 0.008). In PAPS, IgG anti-beta2GPI-oxLig-1 independently predicted PONa (p = 0.02) and IMT of B (p = 0.003), CC, (p = 0.03) and of IC (p = 0.04). In PAPS, PONa inversely correlated to the IMT of B, CC and IC (p = 0.01, 0.02 and 0.003, respectively). IgG anti-beta2GPI-oxLig-1 may be involved in PAPS related atherogenesis via decreased PON activity.

Adult↗
PubMed2006

Oxidized low-density lipoprotein and beta2-glycoprotein I in patients with systemic lupus erythematosus and increased carotid intima-media thickness: implications in autoimmune-mediated atherosclerosis.

Oxidative stress and LDL modification (oxLDL) are early pro-atherogenic events. OxLDL binds beta2GPI producing immunogenic oxLDL/beta2GPI complexes. Antibodies to these complexes have been associated with arterial thrombosis in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Circulating oxLDL/beta2GPI complexes, IgG and IgM antibodies to these complexes were measured by ELISA in 30 SLE patients asymptomatic for cardiovascular disease (mean age 31 years) and 27 age/sex matched healthy controls. Carotid intima-media thickness (IMT) was measured by ultrasound in all patients and controls. Forty-seven percent of SLE presented plaques (median IMT of 0.65 +/- 0.12 mm) while only 7% of the controls had plaques (median IMT of 0.50 +/- 0.04 mm, P < 0.001). Median optical density (OD450nm) for oxLDL/beta2GPI complexes in SLE was 0.244 +/- 0.07, higher than controls (0.174 +/- 0.09, P < 0.001). Median OD for IgG anti-oxLDL/beta2GPI antibodies was also higher in SLE (0.297 +/- 0.26) compared to controls (0.194 +/- 0.07, P < 0.001) while the median OD for IgM antibodies in SLE (0.444 +/- 0.46) was not different than controls (0.326 +/- 0.22, P = 0.267). There was no correlation between IMT and oxLDL/beta2GPI complexes, IgG or IgM antibodies, possibly reflecting the complex interrelationship between these serologic elements and tissue factors in the arterial wall. These results support the hypothesis that oxLDL/beta2GPI complexes and IgG (not IgM) anti-oxLDL/beta2GPI antibodies contribute to the development of autoimmune-mediated atherosclerosis.

Adolescent↗
PubMed2006

Atherogenic oxidized low-density lipoprotein/beta2-glycoprotein I (oxLDL/beta2GPI) complexes in patients with systemic lupus erythematosus and antiphospholipid syndrome.

Oxidized low-density lipoprotein (oxLDL) interacts in vitro with beta2-glycoprotein I (beta2GPI) via LDL-derived specific ligands forming oxLDL/beta2GPI complexes. Circulating oxLDL/beta2GPI complexes have been demonstrated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Autoimmune vascular inflammation and oxidative stress contribute to oxLDL/beta2GPI complex formation. Immunohistochemical staining of atherosclerotic lesions suggest that these complexes are formed in the arterial wall and released into circulation. The demonstration of antibodies to oxLDL/beta2GPI complexes indicates that these complexes are immunogenic, and the coexistence of complexes and antibodies suggest an active pro-thrombotic/pro-atherogenic role in the development of autoimmune vascular complications. Circulating oxLDL/beta2GPI complexes can be measured by ELISA using a monoclonal antibody specific to complexed human beta2GPI to capture beta2GPI bound to oxLDL. An enzyme-conjugated monoclonal antibody to human Apo B 100 allows the specific detection of oxLDL/beta2GPI complexes. OxLDL/beta2GPI complexes were common in SLE and APS patients suggesting an underlying process of inflammation and oxidation. Using oxLDL/beta2GPI complexes as capture antigen, antibodies to oxLDL/beta2GPI can be measured by ELISA. Serum levels of IgG anti-oxLDL/beta2GPI antibodies were significantly higher in SLE patients with APS compared to SLE controls without APS. Further, high titers of these IgG antibodies were observed in APS patients with a history of arterial thrombosis. The presence of circulating oxLDL/beta2GPI complexes and IgG antibodies to these complexes indicates significant vascular injury and oxidative stress as well as an active role in autoimmune-mediated atherothrombosis.

Antibodies, Monoclonal↗
PubMed2005

Lymphocyte subpopulations and intima media thickness in primary antiphospholipd syndrome.

The aim of this study was to evaluate a possible association between lymphocyte subsets and intima media thickness (IMT) of carotid arteries in primary antiphospholipid syndrome (PAPS). We used a cross-sectional study on PAPS patients (n = 18) and healthy controls (n = 16). IgG anti-cardiolipin antibody (aCL), IgG anti-beta2glycoprotein-I (anti-beta2GPI), IgG anti-beta2glycoprotein-I complexed to oxidized low-density lipoprotein (oxLDL) and to a specific oxidized moiety of LDL (oxLig1), and beta2GPI-oxLDL were measured by ELISA. Lymphocyte immunophenotyping was performed using pairs of monoclonal antibodies directly labelled with fluorescein isothiocyanate, or phycoerythrin or phycoerythrin-Texas-red-X. Intima media thickness (IMT) of carotid arteries was determined by high-resolution sonography. Total peripheral blood lymphocytes did not differ between PAPS and controls. Memory CD4+/CD45RO + T cells were lower in PAPS than controls (P = 0.0007) as well as CD16+56+ natural killer cells (P = 0.02). In PAPS memory T CD45RO + cells positively correlated with IgG anti-beta2GPI-oxLigl (P = 0.002) and to IMT of carotid arteries (common carotid P = 0.02, bifurcation P = 0.007). Naive CD4+/CD45RA+ T cells inversely correlated with beta2GPI-oxLDL (P = 0.009). The relation between IgG anti-beta2GPI-oxLig1 and IMT of carotid arteries with memory CD45RO + T lymphocytes suggests a role for the latter in PAPS related atherogenesis.

Adult↗
PubMed2005

Oxidized LDL/beta2-glycoprotein I complexes: new aspects in atherosclerosis.

beta2-glycoprotein I (beta2GPI) is a major antigenic target for antiphospholipid antibodies. Oxidized low-density lipoprotein (oxLDL) is the principal lipoprotein found in atherosclerotic lesions, and it colocalizes with beta2GPI and immunoreactive lymphocytes. oxLDL/beta2GPI complexes appeared in the blood circulation of patients with diseases, such as systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), systemic sclerosis, diabetes mellitus and chronic renal diseases. Thus, the complexes may be associated with systemic and chronic inflammation of the vasculature. IgG anti-oxLDL/beta2GPI complexes autoantibodies and their immune complexes were detected only in SLE/APS patients and in its animal model and were strongly associated with arterial thrombosis. The oxLDL/beta2GPI complexes were internalized by macrophages via IgG anti-beta2GPI antibody-mediated phagocytosis. In contrast, IgM anti-oxLDL antibodies derived from hyperlipidemic mice reduced the incidence of atherosclerosis. The distribution patterns of IgG and IgM anti-oxLDL antibodies in patients suggest the different roles of these antibodies.

Anticoagulants↗
PubMed2003

Hybridomas expressing gammadelta T-cell receptors respond to cardiolipin and beta2-glycoprotein 1 (apolipoprotein H).

Hybridomas expressing murine gammadelta T-cell receptors were found to produce cytokines in response to cardiolipin (CL) and structurally related anionic phospholipids. This response required serum at concentrations related to the amount of CL in cultures. The purified serum factor, beta2-glycoprotein 1 (beta2-GP1) (apolipoprotein H), supported the CL response alone, whereas several other serum proteins and ovalbumin did not. beta2-GP1 is known to form complexes with anionic phospholipids, particularly CL, which are often recognized by pathological autoantibodies. We speculate that gammadelta T cells also recognize such complexes and that the hybridoma response reported here reflects this specificity.

Animals↗
PubMed2003

Oxidized low-density lipoprotein as a risk factor of thrombosis in antiphospholipid syndrome.

Beta2-Glycoprotein I (beta2-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome (APS). We recently reported that oxidized LDL(oxLDL) is subsequently targeted by beta2-GPI and anti-beta2-GPI auto-Abs and that-carboxyl variants of 7-ketocholesteryl esters, such as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and 7-ketocholesteryl-12-carboxy (keto) octadodecanoate (oxLig-2), are ligands for beta2-GPI (J Lipid Re 2001; 42: 697; J Lipid Res 2002; 43: 1486). These beta2-GPI ligands provide an electrostatic interaction between oxLDL and beta2-GPI followed by forming stable complexes (such as Schiff base adducts). The omega-carboxyl function in these ligand is responsible for beta2-GPI binding to oxLDL and the oxLDL-beta2-GPI complexes are anti-beta2-GPI auto-Ab-dependently taken up by macrophages (i.e., by phagocytosis). Our recent observations are consistent with the evidence that beta2-GPI co-localizes with lymphocytes and mononuclear cells in human athero-plaques. Thus, autoimmune thrombogenesis (atherogenesis) is linked to interaction of anti-beta2-GPI Abs with the beta2-GPI-oxLDL complexes. We propose an alternative idea, that an immune response against the beta2-GPI-oxLDL complexes may be involved in mechanisms in the development of atherosclerosis, which has been explained by the theory of 'the response to injury'.

Antigen-Antibody Complex↗
PubMed2001

Expression of vascular endothelial growth factor in tuberculous meningitis.

The pathogenesis of tuberculous meningitis is still unclear. Recently, vascular endothelial growth factor (VEGF) was found to be associated with inflammatory diseases and we found the increased serum level of VEGF in pulmonary tuberculosis. We hypothesized that VEGF might be associated with the pathogenesis of tuberculous meningitis and measured serum and cerebrospinal fluid (CSF) levels of VEGF in 28 patients with tuberculous meningitis and 31 non-tuberculous infectious meningitis patients (13 bacterial meningitis patients, eight fungal meningitis patients and 10 patients with viral meningitis) before therapy. We examined the CSF VEGF levels 3 months after in 12 tuberculous meningitis patients. The serum and CSF levels of VEGF were significantly higher in tuberculous meningitis than in other meningitis. The decrease in titer of CSF VEGF paralleled the clinical improvement of tuberculous meningitis. Immunohistochemical staining of autopsied brains demonstrated the presence of VEGF in the inflammatory mononuclear cells of the dense fibroconnective tissue both in the subarachnoid space and surrounding the vasculitis lesion. We found the expression of VEGF in tuberculous meningitis and think that VEGF reflects its activity.

Adolescent↗
PubMed2001

Circulating levels of MMP-1, -2, -3, -9, and TIMP-1 are increased in POEMS syndrome.

The authors quantitatively measured levels of matrix metalloproteinases (MMP), tissue inhibitor of metalloproteinases (TIMP), and vascular endothelial growth factor (VEGF) in blood samples of POEMS syndrome. Circulating levels of MMP-1, -2, -3, -9, and TIMP-1 were more increased in patients with POEMS syndrome than in patients with other neurologic disorders or in healthy controls. Serum levels of VEGF and TIMP-1 were strongly correlated with each other. Increased circulating levels of MMP-1, -2, -3, -9, and TIMP-1 may lead to a better understanding the pathogenesis of POEMS syndrome.

Endothelial Growth Factors↗
PubMed2001

IgG anti-laminin-1 autoantibody and recurrent miscarriages.

PROBLEM: The present study assesses the clinical significance of anti-laminin-1 auto-antibodies (auto-Abs) in recurrent miscarriages. METHOD OF STUDY: A total of 207 recurrent aborters with a history of two or more consecutive first-trimester miscarriages were tested for the presence of anti-laminin-1 Abs, beta2-glycoprotein I-dependent anticardiolipin Abs, lupus anticoagulants, anti-DNA Abs, and anti-nuclear Abs, before they had conceived again. Recurrent aborters then were followed up during subsequent pregnancies and their outcomes were evaluated relative to their blood test results prior to pregnancy. RESULTS: Fifty-five (31.1%) women out of 177 recurrent aborters were positive for IgG anti-laminin-1 auto-Abs. The levels of IgG anti-laminin-1 auto-Abs in recurrent aborters were significantly higher than those in healthy pregnant women and in healthy non-pregnant women (P = 0.0043 and 0.0073, respectively). The live birth rate of subsequent pregnancies in IgG anti-laminin-1 auto-Abs-positive recurrent aborters was significantly lower than the IgG anti-laminin-1 auto-Abs-negative recurrent aborters (P = 0.0320). There were no specifically significant relationships observed between IgG anti-laminin-1 auto-Abs and other tested auto-Abs. CONCLUSION: IgG anti-laminin-1 auto-Abs are associated with recurrent miscarriages and the subsequent pregnancy outcome of recurrent aborters.

Abortion, Habitual↗
PubMed2001

A specific ligand for beta(2)-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages.

beta(2)-Glycoprotein I (beta(2)-GPI) is a major antigen for antiphospholipid antibodies (Abs) present in patients with the antiphospholipid syndrome (APS). We previously reported that beta(2)-GPI specifically binds to oxidized low density lipoprotein (oxLDL), but not to native low density lipoprotein (LDL). In the present study, a ligand specific for beta(2)-GPI, oxLig-1, was purified from the extracted lipids of oxLDL. The structure of oxLig-1 was shown to be identical to that of synthesized 7-ketocholesteryl-9-carboxynonanoate by mass spectroscopy and nuclear magnetic resonance analyses. Both purified and synthesized oxLig-1 were recognized by beta(2)-GPI and subsequently by anti-beta(2)-GPI auto-Abs, either in enzyme-linked immunosorbent assay (ELISA) or in ligand blot analysis. Binding of liposomes containing oxLig-1 (oxLig-1-liposomes) to mouse macrophages, J774A.1 cells, was relatively low, as compared with that of phosphatidylserine (PS)-liposomes. In contrast, binding of oxLig-1-liposomes was enhanced more than 10-fold in the presence of both beta(2)-GPI and an anti-beta(2)-GPI auto-Ab (WB-CAL-1), derived from (NZW x BXSB) F1 mouse, an animal APS model. Anti-beta(2)-GPI auto-Abs derived from APS patients with episodes of arterial thrombosis were detected in ELISA, using a solid phase oxLig-1 complexed with beta(2)-GPI. We suggest that autoimmune atherogenesis linked to beta(2)-GPI interaction with oxLDL and Abs may be present in APS.

Animals↗
PubMed2000

Marked increase of matrix metalloproteinase 9 in cerebrospinal fluid of patients with fungal or tuberculous meningoencephalitis.

Matrix metalloproteinases (MMPs) are believed to play an essential role in the breakdown of the extracellular matrix macromolecules in the blood-cerebrospinal fluid barrier and blood-brain barrier (BBB). In this study, the levels of MMP-2 and MMP-9 and their common tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) from patients with various meningitides including aseptic, fungal and tuberculous ones. MMP-9 production level in CSF was more increased in subacute meningitis including fungal and tuberculous meningitis than in acute aseptic meningitis and non-inflammatory neurological diseases (NIDs). Enhanced production of MMP-9 was associated with high proteolytic activity detected by gelatin zymography. The MMP-2 and TIMP-1 levels in CSF of subacute meningitis were also higher than those of NIDs. In contrast, the TIMP-2 levels in CSF of either acute aseptic or subacute meningitis were not up-regulated compared with those of NIDs. The central nervous system (CNS) complications (i.e. disturbance of consciousness, psychiatric symptoms, urinary disturbance, etc.) during the course of meningitis showed good correlation with the enhanced production of MMP-9 in CSF. Immunohistochemical studies in tuberculous meningitis demonstrated that the infiltrating mononuclear cells in the meninges were immunoreactive for both MMP-2 and MMP-9. However, the infiltrating mononuclear cells into CNS parenchyma had immunoreactivity for MMP-9, but not for MMP-2. Taken together, those data suggest that MMP-9 in CSF may be a useful marker of encephalitogenecity during the course of subacute meningitis.

Adolescent↗
PubMed2000

Association of autoantibodies against the phosphatidylserine-prothrombin complex with manifestations of the antiphospholipid syndrome and with the presence of lupus anticoagulant.

OBJECTIVE: To clarify the association of autoantibodies against prothrombin with the clinical manifestations of the antiphospholipid syndrome (APS) and with the presence of lupus anticoagulant (LAC). METHODS: We examined 265 patients who visited our autoimmune disease clinic. IgG and IgM antiprothrombin antibodies were tested by enzyme-linked immunosorbent assay (ELISA) as either antiphosphatidylserine-prothrombin complex (aPS/PT) antibodies or as antibodies against prothrombin coated on irradiated ELISA plates (as antigen) (aPT). IgG, IgM, and IgA anticardiolipin (aCL) antibodies and their beta2-glycoprotein I (beta2GPI) dependency were also evaluated by ELISA. LAC was tested by 3 different methods. RESULTS: The presence of aPS/PT, but not of aPT, significantly correlated with the clinical manifestations of APS (odds ratio [OR] 4.39, 95% confidence interval [95% CI] 2.06-9.38), and aPS/PT antibodies were as specific as beta2GPI-dependent aCL for APS (93.1% for both). IgG aPS/PT strongly correlated with the presence of LAC as detected using the dilute Russell viper venom time test (OR 38.2, 95% CI 13.4-109.1). CONCLUSION: Antiprothrombin antibodies are heterogeneous and their clinical relevance depends on the method of detection applied. Positive results on the aPS/PT test can serve as a marker of thrombotic events in patients with autoimmune diseases.

Adolescent↗
PubMed2000

beta(2)-glycoprotein I deficiency: prevalence, genetic background and effects on plasma lipoprotein metabolism and hemostasis.

beta(2)-glycoprotein I (beta(2)-GPI=apolipoprotein H) is an important autoantigen in patients with the antiphospholipid syndrome. It also plays a role in lipoprotein metabolism, such as anti-atherogenic property, triglyceride removal, and enhancement of lipoprotein lipase. Serum beta(2)-GPI concentration of 812 apparently healthy Japanese individuals was measured by sandwich EIA. Two families with complete beta(2)-GPI deficiency were identified. In one family, all affected had increased serum LDL-cholesterol levels or smaller particle sizes of LDL, while the other had no apparent abnormality in lipid metabolism. Individuals investigated had no history of thrombosis or overt abnormalities in hemostatic tests. A thymine corresponding to position 379 of the beta(2)-GPI cDNA was deleted in every beta(2)-GPI deficient individual. The incidence of this heterozygous deficiency determined by RFLP was 6. 3% in Japanese and none in Caucasians. Heterozygotes had significantly lower concentrations of serum beta(2)-GPI than did those without the mutation, yet no significantly different lipid profiles, such as total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apoA-I, apoB and Lp(a), were observed. A low concentration of beta(2)-GPI seemed not to be associated with apparent abnormality in lipoprotein metabolism.

Adult↗
PubMed2000

Proteolytic cleavage of beta(2)-glycoprotein I: reduction of antigenicity and the structural relationship.

Binding of beta(2)-glycoprotein I (beta(2)-GPI)-dependent anticardiolipin antibodies (aCL) derived from antiphospholipid syndrome (APS) is significantly reduced in aCL ELISA due to loss of the phospholipid (PL) binding property of beta(2)-GPI by plasmin treatment. In the present study, the treatment generated a nicked form of beta(2)-GPI and resulted in loss of antigenicity for the autoantibodies detected in ELISA, using an beta(2)-GPI directly adsorbed polyoxygenated carboxylated plate, the assay system of which was not related to PL binding. The nicked form bound to neither Cu(2+)-oxidized low-density lipoprotein (oxLDL) nor to beta(2)-GPI-specific lipid ligands isolated from oxLDL, the result being a complete loss of subsequent binding of anti-beta(2)-GPI autoantibodies. The conformational change in the nicked domain V was predicted from its intact structure determined by an X-ray analysis (implemented in Protein Data Bank: 1C1Z), molecular modeling and epitope mapping of a monoclonal anti-beta(2)-GPI antibody, i.e. Cof-18, which recognizes the related structure. The analysis revealed that novel hydrophobic and electrostatic interactions appeared in domain V after the cleavage, thereby affecting the PL binding of beta(2)-GPI. Such a conformational change may have important implications for exposure of cryptic epitopes located in the domains such as domain IV.

Amino Acid Sequence↗