Istvan Csipo

Oslo University Hospital, Kristiania (historical), Oslo County, Norway

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Publications (38)108.64 Total impact

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    ABSTRACT: A shift in the balance between Th17-cells and regulatory T-cells (Treg) is an important feature of systemic autoimmune diseases (SAID), and may also contribute to their development. Hereby, we assessed the distribution of peripheral Th17 and Treg-cells in patients with undifferentiated connective tissue disease (UCTD), the forerunner of SAIDs and followed these parameters during the development towards definitive SAIDs. Fifty-one UCTD patients were investigated and followed-up for 3 years. Flow cytometry was used to identify and follow three cell-populations: Th17-cells (CD4+IL-17+ T-cells), natural regulatory T-cells (CD4(+)CD25(bright)FoxP3(+); nTregs) and IL-10 producing Type-1 regulatory T-cells (CD4+IL-10+ T-cells; Tr1). Altogether 37.3% of these patients progressed into SAIDs. Th17-cells were increased in UCTD vs. controls, which further increased in those, whom developed SAIDs eventually. The Th17/nTreg ratio gradually increased from controls through UCTD patients, reaching the highest values in SAID-progressed patients. Regarding the Th17/Tr1 ratios, a similar tendency was observed moreover Th17/Tr1 could distinguish between UCTD patients with, or without subsequent SAID progression in a very early UCTD stage. Various immunoserological markers showed association with Th17 and Th17/nTreg at baseline, indicating the consecutive development of a distinct SAID. The derailed Th17/Treg balance may contribute to disease progression therefore could function as a prognostic marker.
    Human immunology 08/2013; · 2.55 Impact Factor
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    ABSTRACT: The aim of the present study was to assess the autoantibody profile, dominant clinical symptoms and cluster characteristics of different Mixed connective tissue disease (MCTD phenotypes. Two-hundred-and-one patients with MCTD were followed-up longitudinally. Five clinical parameters, Raynaud's phenomenon, pulmonary artery hypertension (PAH), myositis, interstitial lung disease (ILD), erosive arthritis and five auto-antibodies besides anti-U1RNP, antiendothelial cell antibodies (AECA), anti-CCP, anti-cardiolipin (anti-CL), anti-SSA/SSB and IgM rheumatoid factor (RF) were selected for cluster analysis. The mean age of patients was 52.9 ± 12.4 years and the mean follow-up of the disease was 12.5 ± 7.2 years. Patients were classified into three cluster groups. Cluster 1 with 77 patients, cluster 2 with 79 patients and cluster 3 with 45 patients. In cluster 1 the prevalence of PAH (55.8%; p < 0.001), Raynaud's phenomenon (92.2%; p < 0.001) and livedo reticularis (24.6%, p < 0.001) was significantly greater than in cluster 2 and 3. In cluster 2, the incidence of ILD (98.7%; p < 0.001), myositis (77.2%; p < 0.001), and esophageal dysmotility (89.8%; p < 0.001) was significantly greater than that in cluster 1 and 3. In cluster 3, anti-CCP antibodies were present in 31 of 45 patients (68.8%) with erosions. Anti-CCP antibodies were present in 37 of 42 patients (88.0%) with erosions. PAH, angina, venous thrombosis was observed in cluster 1 and pulmonary fibrosis in cluster 2, musculosceletal damage, gastrointestinal symptoms and osteoporotic fractures were most frequent in cluster 3. Cumulative survival assessment indicated cluster 1 patients having the worst prognosis. Cluster analysis is valuable to differentiate among various subsets of MCTD and useful prognostic factor regarding the disease course.
    Lupus 08/2012; 21(13):1412-22. · 2.78 Impact Factor
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    ABSTRACT: Celiac disease (CD) is an autoimmune disorder of the small intestine that occurs in genetically predisposed people at all ages. However, it can be associated also to other immunopathological disorders, and may be associated with abnormal histology in segments of the gut other than the small bowel including colonic inflammation. While guidelines for endoscopic investigation of the jejunum are well defined, no indication is defined for colonic investigation. We describe four cases of concurrent CD and microscopic colitis (MC) diagnosed at our department over a 10-year period and analyzed the main features and outcomes of CD in this setting. The symptoms of these patients were improved initially by a gluten-free diet before the onset of MC symptoms. Two of the patients were siblings and had an atypical form of CD. The other two patients with CD and MC also presented with fibrosing alveolitis and were anti-Saccharomyces cerevisiae antibody positive. The co-existence of immune-mediated small bowel and colonic inflammatory and pulmonary diseases are not well-known, and no systematic approach has been used to identify the lifelong patterns of these immune-based diseases. Patients can develop, or present with CD at any stage in life, which can co-exist with other gastrointestinal diseases of (auto-) immune origin. In addition, the familial co-existence and prevalence of MC in patients with a prior diagnosis of CD are unclear. Clinicians managing celiac disease should be aware of these associations and understand when to consider colon investigation.
    World Journal of Gastroenterology 04/2011; 17(16):2150-4. · 2.55 Impact Factor
  • Annals of Hematology 01/2011; 90(10):1227-8. · 2.87 Impact Factor
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    ABSTRACT: Circulating IgG antibodies to oxidized low-density lipoprotein (anti-oxLDL) have been implicated in the development of atherosclerotic plaques. In this study, we investigated the prognostic value of IgG anti-oxLDL antibodies in patients with acute coronary syndrome (ACS). In total 54 patients with ACS and 41 matched healthy controls were involved in this prospective study. Serum IgG anti-oxLDL levels were assessed by ELISA. Higher IgG anti-oxLDL levels were found in patients with ACS versus controls (22.8 ± 23.3 vs. 7.5 ± 5.27 EU/ml, p < 0.0001). IgG anti-oxLDL concentrations were significantly higher in ACS patients with unstable clinical complications (circulatory insufficiency, malignant arrhythmias, recurring ischaemic pain, positive stress-test, need for urgent coronary intervention or sudden cardiac death) versus those without such complications (30.0 vs. 11.7 EU/ml, p < 0.001). Twelve patients (22%) were taking statins. Patients on statins had a significant reduction in clinical complications (33%) versus patients not receiving statin therapy (61%). IgG anti-oxLDL levels were also different in these two groups (11.4 vs. 25.8 EU/ml, respectively; p = 0.03). Serum IgG anti-oxLDL levels correlated with the subsequent development of unstable coronary events. Levels of anti-oxLDL significantly decreased in response to statin therapy, independently of its lipid-lowering effect. Anti-oxLDL antibodies are involved in ACS. The association of anti-oxLDL with unstable clinical complications may indicate the role of this antibody in plaque destabilization.
    Lupus 01/2011; 20(7):730-5. · 2.78 Impact Factor
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    ABSTRACT: The aim of the present study was to evaluate the vitamin D status in patients with mixed connective tissue disease (MCTD) and to determine which clinical symptoms, laboratory parameters and endothelial cell markers are associated with low vitamin D levels. 125 female MCTD patients and 48 age- and sex-matched healthy controls were enrolled in the study. The clinical symptoms, autoantibodies (anti-U1-RNP, anti-cardiolipin - anti-CL and anti-endothelial cell antibody - AECA), serum cytokines (IFN-γ, IL-6, IL-12, IL-23, IL-17 and IL-10), soluble endothelial cell markers (endothelin, thrombomodulin - TM, and von Willebrand factor antigen - vWFAg) and serum lipids (total cholesterol, triglyceride, LDL-C, HDL-C, apolipoprotein A1, and apolipoprotein B) were investigated for an association with vitamin D levels by univariate and multivariate statistical analyses. The mean vitamin D levels were significantly lower in MCTD patients, as compared with the control group (26.16±13.50ng/ml vs. 34.92±9.64ng/ml; p<0.001). In laboratory parameters, vitamin D levels were inversely associated with serum IL-6 (p<0.001), IL-23 (p=0.011), IL-10 (p=0.033) cytokine levels, TM (p=0.001) and endothelin (p=0.033) levels. Low vitamin D levels were also significantly associated with carotid artery intima media thickness (p<0.001), fibrinogen (p=0.010), total cholesterol (p=0.042) and ApoA1 (p=0.004) levels. Among the clinical symptoms, the cardiovascular involvement showed an inverse correlation with vitamin D status in MCTD (p<0.001). The prevalence of vitamin D insufficiency is high in patients with MCTD. We assume that vitamin D insufficiency along with inflammatory parameters and lipid abnormalities may provoke cardiovascular events.
    Autoimmunity reviews 12/2010; 10(6):317-24. · 6.37 Impact Factor
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    ABSTRACT: Serum cytokines play an important role in the pathogenesis of myositis by initiating and perpetuating various cellular and humoral autoimmune processes. The aim of the present study was to describe a broad spectrum of T- and B-cell cytokines, growth factors and chemokines in patients with idiopathic inflammatory myopathies (IIMs) and healthy individuals. A protein array system, denoted as multiplex cytokine assay was utilized to measure simultaneously the levels of 24 circulating cytokines, including B-cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) of patients with IIMs and healthy individuals. Additionally, correlational clustering and discriminant function analysis (DFA), two multivariate, supervised analysis methods were employed to identify a subset of biomarkers in order to describe potential functional interrelationships among these pathological cytokines. Univariate analysis demonstrated that a complex set of immune and inflammatory modulating cytokines are significantly up-regulated in patients with IIMs relative to unaffected controls including IL-10, IL-13, IFN-α, epidermal growth factor (EGF), VEGF, fibroblast growth factor (FGF), CCL3 [macrophage inflammatory protein (MIP-1α)], CCL4 (MIP-1β) and CCL11 (eotaxin), whereas G-CSF was significantly reduced in IIM patients. Correlational clustering was able to discriminate between, and hence sub-classify patients with IIMs. DFA identified EGF, IFN-α, VEGF, CCL3 (MIP-1α) and IL-12p40, as analytes with the strongest discriminatory power among various myositis patients and controls. Our findings suggest that these factors modulate myositis pathology and help to identify differences between subsets of the disease.
    Rheumatology (Oxford, England) 10/2010; 49(10):1867-77. · 4.24 Impact Factor
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    ABSTRACT: The aim of the present study was to investigate the association between cardiovascular risk factors and endothelial dysfunction in patients with mixed connective tissue disease (MCTD) and to determine which biomarkers are associated with atherosclerotic complications, such as cardiovascular disease. Fifty MCTD patients and 38 healthy age-matched and sex-matched controls were enrolled in this study. In order to describe endothelial dysfunction, we assessed flow-mediated dilation (FMD), nitrate-mediated dilation (NMD) and carotid artery intima-media thickness (IMT). We investigated FMD of the brachial artery after reactive hyperemia and NMD after sublingual nitroglycerin administration, while the IMT of the common carotid artery was determined by ultrasound. Anti-U1 ribonucleoprotein (anti-U1RNP) antibodies, anti-cardiolipin (anti-CL) antibodies, anti-endothelial cell antibody (AECA) and endothelial cell markers, such as soluble thrombomodulin (TM) and von Willebrand factor antigen (vWFAg), were assessed. The endothelium-dependent vasodilation (FMD) was significantly impaired in patients with MCTD, as compared with controls (%FMD: 4.7+/-4.2% vs. 8.7+/-5.0%; P<0.001), while the percentage NMD did not differ (%NMD: 14.3+/-6.6% vs. 17.1+/-6.7%; P=0.073). Mean carotid IMT values were higher in patients than in controls (IMT: MCTD, 0.64+/-0.13 mm vs. controls, 0.53+/-0.14 mm; P<0.001). FMD negatively correlated with disease duration, the levels of apolipoprotein A1, the paraoxonase-1 activity, and systolic blood pressure in MCTD patients. The percentage FMD was significantly lower in MCTD patients with cardiovascular diseases (CVD), than in those without CVD (%FMD: 3.5+/-2.9 vs. 5.8+/-4.8, P<0.0002), while percentage NMD did not differ between patients with and without CVDs. Serum levels of autoantibodies (anti-U1RNP, AECA and anti-CL) were significantly higher in MCTD patients and differed between MCTD patients with and without CVD. Endothelial cell markers such as soluble TM (12.2+/-8.1 ng/ml vs. 3.2+/-1.3 ng/ml; P<0.001) and vWFAg (224.1+/-115% vs. 89.4+/-27.1%, P<0.001) were the highest in MCTD patients with CVD. FMD is a reliable sensitive marker of endothelial cell dysfunction in MCTD. Beside the traditional risk factors, anti-U1RNP, AECA and anti-CL antibodies may be important not only in the pathogenesis of MCTD but in the induction of endothelial cell activation, and may play crucial roles in the development of early atherosclerosis in MCTD.
    Arthritis research & therapy 05/2010; 12(3):R78. · 4.27 Impact Factor
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    ABSTRACT: The strongest predictive factor for the development of interstitial lung disease (ILD) in myositis (IIM) patients is the presence of different antisynthetase antibodies. The aim of this study was to compare the clinical characteristics, radiological findings and therapeutic response between the anti-SS-A positive and negative antisynthetase syndrome (ASS) patients. A prospective study of 315 IIM patients was conducted including 27 anti-Jo-1 positive ASS patients. Mean disease duration was 46.6 (range 4-198) months. All patients fulfilled the classification criteria for IIM. All patients underwent chest radiography, pulmonary function tests and HRCT at he time of diagnosis and 6 months after the immunosuppressive therapy. Routine laboratory tests, RF, ANA, anti-ENA, anti-SS-A, anti-histidyl-transfer RNA antibody (Jo-1) measurements were performed in all patients. ILD was found to be present in 70.4% of ASS patients. The anti-SS-A negative ASS group had a more frequent association with alveolitis and responded well to immunosuppressive therapy (p < 0.05). HRCT scan showed more fibrosis in the SS-A positive group. 15.8% of patients died due to pulmonary or cardiac complications. In conclusion, coexistence of anti-SS-A and anti-Jo-1 antibody may be a good predictor for a more coarse and severe ILD in IIM patients who require a more aggressive approach in therapy.
    Rheumatology International 03/2009; 29(9):989-94. · 2.21 Impact Factor
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    ABSTRACT: Presence of autoantibodies to alfa-fodrin was investigated in patients with Sjögren's syndrome (n = 61), Hashimoto thyroiditis (n = 27), Sjögren's syndrome associated with Hashimoto thyroiditis (n = 31) and in healthy persons (n = 77). In each group, level of alfa-fodrin antibodies was higher than in the controls. There was no significant difference in their presence either between patients with Hashimoto thyroiditis with or without Sjögren's syndrome, or-in IgA isotype-between Sjögren's and Hashimoto thyroiditis patients. Correlation was found between the level of IgG alfa-fodrin and anti-thyroglobulin antibodies. Based on these findings, fodrin can be associated with both endocrine and exocrine glandular secretion. Antibodies to alfa-fodrin might have a role in the pathogenesis of Hashimoto thyroiditis concerning the "final common effectory pathway", secretion. Alfa-fodrin antibodies can be good markers of secretory disorders. Assessment of these autoantibodies might help the diagnosis and follow-up of patients with impaired secretory capability of not only autoimmune origin.
    Rheumatology International 05/2008; 28(11):1169-72. · 2.21 Impact Factor
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    ABSTRACT: Mixed connective tissue disease (MCTD) is a systemic inflammatory autoimmune disease. The connection between inflammatory measures and atherosclerosis in MCTD has not been described. Paraoxonase (PON) is known to have an antioxidant function. We evaluated lipid profiles and PON activity in patients with MCTD. Thirty-seven patients with MCTD were enrolled. Patients had taken no antihyperlipidemic drugs in the past 2 months. Thirty healthy individuals served as controls. The mean age of patients was 51.2 +/- 9.5 years; disease duration was 11.0 +/- 7.2 years. PON activity was determined with spectrophotometry, von Willebrand factor (vWF) antigen was investigated with the immunoturbidimetry method, and thrombomodulin and antiendothelial cell antibody (AECA) measurements were carried out by ELISA. PON activity in patients with MCTD was significantly lower than in the controls (patients 118.5 +/- 64.6 U/l, controls 188.0 +/- 77.6; p < 0.001). Arylesterase activity was significantly reduced in patients (p < 0.001). Reduction of PON activity showed a close correlation with the age of the patients, duration of the disease, and vascular events (eye, cardiac, cerebral). There was a close association between the low PON activity and endothelial cell activation markers (thrombomodulin, vWF, AECA). Our results indicate that in patients with MCTD there is an increased risk for atherosclerosis. In the development of atherosclerosis, besides the elevated levels of cholesterol and triglyceride, reduced PON concentrations and PON activity may play a crucial role.
    The Journal of Rheumatology 02/2008; 35(2):237-43. · 3.26 Impact Factor
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    ABSTRACT: Human serum paraoxonase (PON1) protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low-density lipoprotein (oxLDL); therefore, it may protect against atherosclerosis. PON1 activity and polymorphisms have been inconsistently associated with carotid artery disease. The goal of this study was to clarify the role of PON1 activity and phenotype on carotid artery disease and its correlation with some inflammatory and immune markers in subjects under 55 years with early-onset carotid atherosclerosis. Sixty patients with occlusive carotid artery disease and 30 healthy controls were enrolled. Intima-media thickness (IMT) was measured by high-resolution ultrasound of both common carotid arteries. Anti-oxLDL antibody levels were determined by ELISA. In the whole study population we found a negative correlation between PON1 activity and IMT (r = -0.27, p = 0.011), and between salt-stimulated PON1 activity and IMT (r = -0.24, p = 0.02). Both PON1 activity and salt-stimulated PON1 activity negatively correlated with anti-oxLDL levels (r = -0.28, p = 0.008; r = -0.26, p = 0.01). PON1 activity was lower in patients compared to controls; however, the difference was not significant.PON1 phenotype distribution of patients and controls did not differ significantly. The importance of PON1 activity as a predictive risk factor for early-onset occlusive carotid artery disease should be assessed in future studies.
    Cerebrovascular Diseases 02/2008; 25(1-2):122-8. · 2.81 Impact Factor
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    ABSTRACT: The aim was to measure the level of antibodies to oxidized LDL (oxLDL) and C-reactive protein (CRP) in the serum of patients with acute coronary syndrome (ACS). The results were correlated with data obtained from patients with stable coronary artery disease (stable CAD) and healthy controls. Thirty-three patients with ACS and 62 stable CAD patients were enrolled in the study. Fifty healthy individuals served as controls. The evaluation of anti-oxLDL autoantibodies was performed by ELISA, while CRP levels were measured by turbidimetry. The level of antibodies to oxLDL was significantly higher in both groups of patients with ACS and stable CAD compared to controls. The comparison between the acute and stable groups showed that anti-oxLDL levels were higher in the acute group, but because of high SD, the difference was not significant. By performing group analysis, anti-oxLDL levels were found to be significantly higher in ACS patients with unstable clinical state (circulatory insufficiency, malignant arrhythmias, recurring ischemic pain, need for urgent coronary intervention and death). CRP level in patients with ACS was significantly higher than in those with stable CAD. A positive correlation was found between anti-oxLDL antibodies and CRP levels both in patients with ACS and stable CAD. The association between the two biomarkers was stronger in the ACS group. In conclusion, our findings support the notion that the presence of antibodies to oxLDL, a plaque-specific antigen, plays a major role as a predictor of complicated manifestations of ACS.
    Thrombosis and Haemostasis 09/2007; 98(2):413-9. · 6.09 Impact Factor
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    ABSTRACT: Soluble, human low affinity Fcgamma receptors, such as sFcgammaRII and sFcgammaRIII, are known to play a pathologic role in different diseases. Sandwich ELISAs had previously been applied for the specific detection and determination of these soluble receptors. In these ELISAs, commercial monoclonal antibodies (Ab) were used as capture antibodies with monoclonal or polyclonal antibodies serving as detector Abs. Increased levels of cell-free FcgammaRIII have been detected in patients with lupus but the functions and levels of sFcgammaRII have not been fully characterized yet. The aim of this work was to determine the ligand binding capacities and levels of soluble FcgammaRII and FcgammaRIII in sera of patients with systemic lupus erythematosus (SLE). Moreover, correlation between the levels of sFcgammaRII and sFcgammaRIII and the clinical activity of the disease were investigated. Sera of 47 patients with SLE, and 51 healthy subjects were analyzed. In the newly developed indirect sandwich ELISAs commercial monoclonal anti-FcgammaRs are used as capture antibodies, and the ligand of FcgammaRII and FcgammaRIII, an artificial immune complex (IC), serves as a detection component replacing the second antibodies used in previous methods. The ligand binding capacity of both soluble FcgammaRII and sFcgammaRIII were elevated in the sera of SLE patients compared to control samples. This increase was significant in patients with the active disease (n = 30; p < 0.01). It was also revealed that a substantial part of the soluble Fcgamma receptors in these patients was bound in vivo to circulating IC. These newly developed ELISAs are probably more phisiologically relevant than other previous assays because they detect the circulating receptors on the basis their in vitro ligan binding capacities. Therefore this method can separately measure the levels of the soluble, free FcgammaRs and those bound circulating IC in vivo.
    Autoimmunity 05/2007; 40(3):165-8. · 2.77 Impact Factor
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    ABSTRACT: Inflammatory processes have importance in atherosclerosis. We evaluated if subjects below 55 years of age with occlusive carotid artery disease have higher serum levels of antibodies against oxidized LDL and endothelial cells and the chemokines MCP-1 and RANTES than age matched subjects without atherosclerosis. Sixty patients with occlusive carotid artery disease (stenosis or occlusion) and 30 age-matched controls participated in the study. We measured the degree of carotid artery stenosis and intima-media thickness (IMT) by duplex ultrasound. White blood cell count (WBC), C-reactive protein (CRP), and fibrinogen levels were significantly higher in patients (means+/-SD: 7.5+/-1.8 vs. 6.1+/-1.1 G/L, p<0.001; 7.7+/-20.7 vs. 2.5+/-1.9 mg/L, p=0.015; and 3.7+/-0.9 vs. 3.1+/-0.5 g/L, p<0.001, respectively). Antibody levels against oxidized LDL and endothelial cells (21.1+/-22.9 and 19.9+/-15.3 EU/mL, p=0.6; and 19+/-15 vs. 20+/-9 U/mL, p=0.07) and RANTES and MCP-1 levels (72.4+/-32.3 vs. 73.8+/-27.3 ng/mL, p=0.7; and 468+/-1041 vs. 318+/-131 pg/mL, p=0.7) did not differ significantly between patients and controls and did not correlate with IMT. Higher levels of WBC, CRP, and fibrinogen suggest an ongoing inflammation in early-onset carotid atherosclerosis, but increased IMT is not associated by the elevation of serum levels of chemokines and antibodies evaluated in this study.
    Cytokine 02/2007; 37(1):44-50. · 2.52 Impact Factor
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    ABSTRACT: Coeliac disease is strongly associated with human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes. The diagnosis is based on demonstrating crypt-hyperplastic villous atrophy, endomysial or transglutaminase antibodies and correlation of disease activity with gluten intake. To evaluate the clinical utility of HLA-DQ typing, when coeliac disease diagnosis had previously been established solely by histology. HLA-DQ alleles, endomysial and transglutaminase antibodies were investigated and histology slides reviewed in 70 patients diagnosed 2-25 years earlier by small-intestinal biopsy but without measuring endomysial or transglutaminase antibodies. Patients without DQ2 or DQ8 or without unequivocal villous atrophy were followed-up on free diet by using serology and biopsies. All 40 endomysial/transglutaminase antibodies positive patients carried DQ2 or DQ8, and 39 of them had severe villous atrophy. Only 56% of patients without endomysial or transglutaminase antibodies positivity had DQ2 or DQ8 (P < 0.001). Seropositivity and relapse developed in 4 of 11 DQ2 positive but in none of 15 DQ2 and DQ8 negative patients on long-term gluten exposure. Coeliac disease diagnosis based solely on histology is not always reliable. HLA-DQ typing is important in identifying DQ2 and DQ8 negative subjects who need revision of their diagnosis, but it does not have additive diagnostic value if endomysial positivity is already known.
    Alimentary Pharmacology & Therapeutics 11/2006; 24(9):1395-402. · 4.55 Impact Factor
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    ABSTRACT: We investigated the clinical characteristics and immunoserological alterations in patients with mixed connective tissue disease (MCTD) associated with pulmonary arterial hypertension (PAH). Anti-U1RNP autoantibodies, anti-endothelial cell antibodies (AECA) and serum thrombomodulin (TM) as well as von Willebrand factor antigen (vWFAg) concentrations were measured in 25 patients with MCTD associated with PAH and in 154 MCTD patients without PAH. The results showed that the probability of survival was lower in MCTD patients with PAH than in the 154 MCTD-non-PAH patients (5-year survival rate in MCTD with PAH: 73%, versus 96% in MCTD-non-PAH; P < 0.01). AECA were more frequently present in the sera of MCTD patients with PAH than in MCTD-non-PAH (P < 0.001). Serum TM and vWFAg levels were higher in MCTD-PAH patients than in MCTD-non-PAH patients (TM: P < 0.001; vWFAg: P < 0.001). Significant correlation was noticed between the quantity of AECA and TM level (r = 0.466) as well as the quantity of AECA and vWFAg level (r = 0.550). In conclusion, our results suggest that in MCTD the presence of AECA and endothelial cell activation may play a role in the development of PAH and in the maintenance of obliterative vascular processes.
    Scandinavian Journal of Immunology 07/2006; 64(1):69-76. · 2.20 Impact Factor
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    ABSTRACT: This paper describes a 61-year-old woman who presented with mixed connective tissue disease, which was complicated by the development of pulmonary arterial hypertension (PAH). Her condition worsened rapidly, with development of haemopthysis, tachypnoe and cardiac arrest. Doppler echocardiography showed a high systolic pulmonary arterial pressure (98 mmHg), confirmed by the right heart catheterization. Vasculopathy of the pulmonary artery vessels was detected following open lung biopsy. No pulmonary embolism was found. Because of suspicion of flare of her underlying disease, which leads to PAH, immunosuppressive treatment was started with high doses of corticosteroid and cyclophosphamide, in combination with the prostacyclin analogue, Iloprost, and low molecular weight heparin. The therapy resulted in slow recovery over 6 weeks, with control echocardiography showing normalization of the high pulmonary pressure, and the patient being capable of returning to everyday activities.
    Rheumatology International 02/2006; 26(3):264-9. · 2.21 Impact Factor
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    ABSTRACT: Immune-inflammatory processes play important role in the pathogenesis of atherosclerosis. Therefore, increasing attention is focused on rheumatic diseases with chronic inflammation, such as systemic lupus erythematosus. Besides direct influences, inflammation may modify the development of atherosclerosis by other mechanisms. To examine paraaoxonase activity and lipid profile in lupus patients. Authors entered 37 definitive lupus patients and 30 age- and sex-matched normal controls into the present study. Patients' age was 40.8 +/- 13.9 year, follow-up time 6.7 +/- 6.2 year, disease activity index 2.8 +/- 3.4. Lipid parameters (total cholesterol, LDL-C, HDL-C, Apo-AI and ApoB) were determined by an autoanalyser, paraoxonase and arylesterase activities were measured spectrophotometrically. Phenotypic distribution of the enzyme was determined by dual substrate method. Anti-oxLDL was measured by ELISA method, CRP by automatised immunoassay. Statistical analysis was performed by SPSS program. Despite of long disease duration and low inflammatory activity authors found significantly (p < 0.001) decreased paraoxonase activity (121.9 +/- 65.9 U/mL) (p < 0.001) in lupus as compared to control (188.1 +/- 78.9 U/mL), which correlated with the presence of atherothrombotic complications (p = 0.009). High activity BB phenotype did not occur in lupus. Lipid parameters and arylesterase activity were within normal range in both groups. No significant correlation was found between paraoxonase activity and disease activity index, dose of corticosteroid therapy, CRP and anti-oxLDL level. Arylesterase activity did not differ in lupus and control groups. Present results suggest that other mechanisms, e.g. antibodies, genetic factors, alteration in the distribution of HDL-subfractions or ensyme abnormalities in HDL remodelling may stand at the background of reduced paraoxonase activity in lupus.
    Orvosi Hetilap 11/2005; 146(47):2395-402.
  • Arthritis & Rheumatology 10/2005; 52(9):2950-1. · 7.48 Impact Factor