192 results on '"Tarr T"'
Search Results
52. Similarities and differences between pediatric and adult patients with systemic lupus erythematosus.
- Author
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Tarr, T, Dérfalvi, B, Győri, N, Szántó, A, Siminszky, Z, Malik, A, Szabó, A J, Szegedi, G, and Zeher, M
- Subjects
- *
SYSTEMIC lupus erythematosus , *IMMUNOLOGIC diseases in children , *INTRAVENOUS immunoglobulins , *PHOSPHOLIPID antibodies , *MATERNAL age - Abstract
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with highest prevalence among women of childbearing age. However, children younger than 16 years also can develop SLE (childhood-onset lupus/juvenile-type SLE). The aim of our study was to compare the clinical course of adult and pediatric-onset SLE. Data from 342 adult patients followed at the University of Debrecen, Hungary, and 79 children documented in the Hungarian National Pediatric SLE registry were analyzed using hospital medical records. Organ manifestations, laboratory parameters, and immunoserological characteristics were reviewed and the results were evaluated using SPSS for Windows software.Gender distribution was not significantly different between groups with disease starting in childhood vs adulthood. The prevalence of the following manifestations was significantly higher for pediatric than for adult-onset disease including: lupus nephritis (43% pediatric vs 26.4% for adult-onset), hematological disorders (57% vs 36.4%), photosensitivity (20% vs 9%), butterfly rash (61% vs 35.5%) and mucosal ulceration (11.4% vs 4%). For adult-onset SLE, neurological symptoms (30% vs 6%) and polyarthritis (86% vs 68%) occurred significantly more frequently than in children. Anti-SSA, anti-SSB and antiphospholipid antibodies were detected at significantly higher levels in adult-onset patients compared to those in pediatrics. Children were more commonly given high-dose intravenous immunoglobulin treatment (6.3% vs 0.6%) and mycophenolate mofetil (15.2% vs 5.3%) than adults.These results suggest that pediatric and adult-onset SLE differ in multiple aspects, and it is important to recognize these differences for optimal treatment and prognosis of these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
53. Decreased apopto-phagocytic gene expression in the macrophages of systemic lupus erythematosus patients.
- Author
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Majai, G, Kiss, E, Tarr, T, Zahuczky, G, Hartman, Z, Szegedi, G, and Fésüs, L
- Subjects
SYSTEMIC lupus erythematosus ,GENE expression ,MACROPHAGES ,AUTOIMMUNITY ,PHAGOCYTOSIS ,APOPTOSIS ,PATIENTS - Abstract
The clearance of apoptotic cells has an important role in the maintenance of tissue homeostasis and in the protection of tissues from the inflammatory and immunogenic contents of dying cells. A defect in the recognition and phagocytosis of apoptotic cells contributes to the development of chronic inflammation and autoimmune disorders. We have observed that compared with healthy donors, differentiated macrophages from patients with untreated systemic lupus erythematosus (SLE) showed decreased phagocytosis of apoptotic neutrophils. A TaqMan Low Density Array was designed to determine the mRNA expression levels of 95 apopto-phagocytic genes in differentiated non-phagocytosing and phagocytosing macrophages. In the macrophages of clinically and immunoserologically active SLE patients, 39 genes were expressed at lower levels than in the control macrophages. When inactive patients were compared with those with minor immunoserological abnormalities or patients in an immunoserologically active state, a relationship was observed between the altered gene expression profile and the disease state. In the macrophages of patients with engulfing apoptotic cells, an upregulation of genes involved in inflammation, autophagy, and signaling was observed. These results indicate that novel immune-pathological pathways are involved in SLE and suggest targets for potential therapeutic modulation. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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54. Divergent Effects of Rapamycin on Mouse and Rat Cells Following Mitogenic Stimulation
- Author
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Olivera, D.L., primary, Kaplan, J.M., additional, Newman-Tarr, T., additional, Ruggieri, E.V., additional, and Badger, A.M., additional
- Published
- 1993
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55. A COMPARISON OF THE HEMODYNAMIC EFFECTS OF PIROXIMONE WITH DOBUTAMINE FOLLOWING CARDIAC SURGERY
- Author
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Tarr, T., primary, Shearer, E., additional, and Moore, N., additional
- Published
- 1992
- Full Text
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56. The immunopathological role of vitamin D in patients with SLE: data from a single centre registry in Hungary.
- Author
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Szodoray, P, Tarr, T, Bazso, A, Poor, G, Szegedi, G, and Kiss, E
- Subjects
- *
SYSTEMIC lupus erythematosus , *VITAMIN D deficiency , *AUTOIMMUNE diseases , *CARDIOVASCULAR diseases - Abstract
Objectives: Disproportionate vitamin D levels may play an important role in the development of certain systemic autoimmune and rheumatic diseases. The aim of the present study was to investigate the prevalence of vitamin D insufficiency in patients with systemic lupus erythematosus (SLE) and to compare serological and clinical parameters in patients with different vitamin D levels from a single centre registry in Central-Eastern Europe. Methods: A total of 177 patients with SLE were enrolled in the study. 25-Hydroxyvitamin D [25(OH)D] levels were measured by chemiluminescent immunoassay ( CLIA). Autoantibody profiles, complement 3 (C3) and C4, clinical symptoms, and disease activity (using the SLE disease activity index, SLEDAI) of the patients were assessed. Results: Vitamin D concentration in the total SLE group investigated was 26.88 ±± 13.25 ng//mL. Vitamin D levels were normal (≥≥ 30 ng//mL) in 18.1%% of patients, insufficient (15--30 ng//mL) in 44.6%%, and deficient (< 15 ng//mL) in 37.3%%. The vitamin levels were significantly reduced in postmenopausal compared to premenopausal patients (p == 0.02). Patients with pericarditis (p == 0.013), neuropsychiatric diseases (p == 0.01), and deep vein thrombosis (p == 0.014) had reduced vitamin D levels. SLEDAI score was significantly increased in patients with reduced vitamin D levels (p == 0.038). Anti-double-stranded (ds)DNA autoantibody concentrations increased from normal to insufficient and further increased from insufficient to deficient patient subsets (p == 0.021). Anti-Smith antigen (anti-Sm) concentrations increased (p < 0.001), C4 levels decreased (p == 0.027), and immunoglobulin (Ig)G concentration increased (p == 0.034) in patients with reduced vitamin D levels. Conclusions: Our data suggest that vitamin D deficiency in SLE may play a role in perpetuation of the disease. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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57. Measurement of natural (CD+CDhigh) and inducible (CD4+IL-10+) regulatory T cells in patients with systemic lupus erythematosus.
- Author
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Barath, S., Aleksza, M., Tarr, T., Sipka, S., Szegedi, G., and Kiss, E.
- Subjects
SYSTEMIC lupus erythematosus ,T cells ,CELL populations ,PATIENTS ,IMMUNOMODULATORS ,FLOW cytometry - Abstract
Abnormalities of regulatory T cells may play an important role in the loss of self-tolerance, which is a major characteristic of lupus. The objective of this study was to determine the ratio and the number of natural CD4
+ CD25high Foxp3+ and inducible CD4+ IL-10+ regulatory T cells in lupus patients and to search correlation with disease activity. Seventy-two Hungarian lupus patients were enrolled in the study. Fourty-one age- and sex matched healthy donors served as controls. Flow cytometry was used for the quantification of CD4+ CD25high Foxp3+ (nTreg) and CD4+ IL-10+ (iTreg) cells. The ratio (3.06 ± 1.45%) and the number (0.019 ± 0.012 × 109 ⁄L) of nTreg cells decreased in lupus significantly (P < 0.001 in both) as compared to normal controls (4.26 ± 1.01% and 0.039 ± 0.017 × 109 ⁄L). The ratio of iTreg cells were significantly higher in patients than in controls (20.92 ± 14.02% versus 15.49 ± 11.65%, P < 0.03), but the number of these cell type did not differ in significant manner (0.314 ± 0.236 × 109 ⁄L versus 0.259 ± 0.183 × 109 ⁄L). The 19 active patients were characterised by significantly higher disease activity index (SLEDAI 8.63 ± 2.95 versus 1.74 ± 1.68, P < 0.001) and anti-DNA concentration (117.85 ± 145.89 versus 37.36 ± 68.85 IU/mL, P = 0.001) as compered to the 52 inactive patients. Furthermore, active patients required higher dose of methylprednisolon than inactive ones (14.8 ± 10.6 versus 4.8 ± 3.4 mg/day, P = 0.001). However, we did not find statistical significant difference in the number and ratio of the examined cell populations regarding to disease activity. Altered ratio and number of both natural and inducible regulatory T cells may play a role in the pathogenesis of lupus. There are small but appreciable difference in the number of regulatory T cells between inactive patients and healthy controls. It suggests that immunoregulatory deficiencies are present in the inactive stage of the disease also. [ABSTRACT FROM AUTHOR]- Published
- 2007
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58. A121 A COMPARISON OF THE PDE INHIBITOR ENOXIMONE WITH DOBUTAMINE FOLLOWING MITRAL VALVE REPLACEMENT
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Tarr, T. J., primary, Frazer, R. S., additional, Moore, N. A., additional, and Desmond, M. J., additional
- Published
- 1990
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59. A120 HEMODYNAMIC EFFECTS OF THE PDE INHIBITOR PIROXIMONE TO ASSIST IN WEANING FROM CPB
- Author
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Tarr, T. J., primary, Frazer, R. S., additional, Moore, N. A., additional, and Desmond, M. J., additional
- Published
- 1990
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60. COMPARISON OF ENOXIMONE WITH DOPAMINE FOLLOWING MITRAL VALVE SURGERY.
- Author
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TARR, T. J., primary, JEFFREY, R. R., additional, COWEN, M. E., additional, and KENT, A. P., additional
- Published
- 1990
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61. Visomat S sphygmomanometer for home blood pressure management.
- Author
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CHANNING, N. A., TARR, T. J., and CRAVEN, A. H.
- Abstract
This study was designed to assess the accuracy of the Visomat S home blood pressure recorder. Both the conventional mercury sphygmomanometer and intra-arterial pressure transducer were used as standards for comparison. The accuracy of the Visomat was assessed for 24 normotensive subjects and then for 24 hypertensive subjects using the conventional sphygmomanometer as the standard for comparison. The Visomat was found to give an accurate measure of the systolic and diastolic (phase V) pressures registered by the sphygmomanometer in both these groups of subjects. In a further study on eight subjects, it was shown that the Visomat also gave an accurate assessment of systolic and diastolic pressures measured directly with intra-arterial catheters. The design of the Visomat makes it very convenient for home blood pressure recording. It can be used by a patient unaided and a minimum of skill is required to obtain a reading. With its accuracy confirmed, the Visomat is a useful instrument for home blood pressure management. [ABSTRACT FROM PUBLISHER]
- Published
- 1982
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62. Inhibition of interleukin-1-induced proteoglycan degradation and nitric oxide production in bovine articular cartilage/chondrocyte cultures by the natural product, hymenialdisine.
- Author
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M, Badger A, N, Cook M, A, Swift B, M, Newman-Tarr T, M, Gowen, and M, Lark
- Abstract
The effects of hymenialdisine (SK&F 108752) were evaluated on interleukin-1 (IL-1)-induced proteoglycan (PG) degradation, PG synthesis, nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) gene expression in bovine articular cartilage (BAC) and/or cartilage-derived chondrocytes. Cartilage disks from 0- to 3-month-old calves were treated with IL-1alpha or retinoic acid. PG release was determined by measuring glycosaminoglycan release, and nitrite production was measured as a readout for NO. Inhibition of iNOS gene expression was measured by Northern blot analysis in IL-1alpha-stimulated, cartilage-derived chondrocytes. To measure PG synthesis, chondrocytes were established in alginate beads and treated with hymenialdisine, and then [(35)S]sulfate incorporation into PGs was determined. Hymenialdisine inhibited IL-1alpha-stimulated PG breakdown in BAC in a dose-related manner with an IC(50) of approximately 0.6 microM. Herbimycin, a protein tyrosine kinase inhibitor, also inhibited PG breakdown, whereas RO 32-0432, a protein kinase C inhibitor, had no effect. Both hymenialdisine and herbimycin also were able to inhibit retinoic acid-stimulated PG release. IL-1alpha-stimulated NO production in BAC was inhibited by hymenialdisine and herbimycin at similar concentrations. The effect on iNOS gene expression was determined by Northern blot analysis in chondrocytes grown in monolayer, and inhibition by hymenialdisine was observed with an IC(50) of approximately 0.8 microM. In chondrocytes cultured in alginate beads, IL-1alpha inhibited PG synthesis, whereas hymenialdisine stimulated synthesis at low concentrations (0.6 and 1.25 microM), and higher doses (2.5 microM) were not stimulatory. Compounds with this profile may have utility in the treatment of osteoarthritis.
- Published
- 1999
63. Immunomodulatory effects of vitamin D in Hungarian SLE patients
- Author
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⁎, A., Tarr, T., Szegedi, G., Poor, G., and Kiss, E.
- Published
- 2009
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64. Comparison of anti-emetics.
- Author
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Hammond, J., Elwood, R., Tarr, T., and Simpson, D.
- Published
- 1985
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65. Radioisotope $sup 238$Pu: forecasted needs, availability, and cost
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Tarr, T
- Published
- 1975
66. DETERMINATION OF FREE CARBON IN BORON CARBIDE: A PROGRESS REPORT.
- Author
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Tarr, T
- Published
- 1972
67. Clinical Features and Survival Analysis of Lupus Nephritis among Patients with Systemic Lupus Erythematosus: A Three-Decade-Long Retrospective Cohort Study.
- Author
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Perge B, Papp G, Bói B, Nagy N, Gáspár-Kiss E, and Tarr T
- Abstract
Background/Objectives: Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). The aim of our retrospective cohort study was to compare the clinical characteristics, therapy, survival, causes of death, and prognostic factors of LN and non-LN lupus patients. Moreover, we compared a wide spectrum of clinical data of LN patients diagnosed before and since 2005 to determine any changes in disease course and outcomes. Methods: We assessed the clinical and laboratory data of 384 SLE patients, out of whom, 127 patients were diagnosed with LN between 1990 and 2020. Results: Based on our observations, discoid LE, subacute cutaneous LE, antiphospholipid syndrome, Sjögren's syndrome, and rheumatoid arthritis were more common in non-LN patients, while anemia and anti-RNP positivity were more frequent in LN patients. Development of LN did not affect survival rates; male sex and presence of APS were negative prognostic parameters in the non-LN group while achieving remission was a positive prognostic factor in both groups. Death caused by sepsis was more prevalent in the LN group. Serositis and neurological manifestations occurred less frequently in LN patients diagnosed after 2005. The use of mycophenolate mofetil became more common, and the cumulative corticosteroid dose decreased. The SLICC Damage Index score also decreased. Conclusions: Our study demonstrated that the disease course has changed in recent years, and the main therapeutic goal in both SLE and lupus nephritis should be to achieve remission because this significantly improves long-term prognosis and patient survival.
- Published
- 2024
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68. Antiphospholipid Antibodies Are Major Risk Factors for Non-Thrombotic Cardiac Complications in Systemic Lupus Erythematosus.
- Author
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Nagy N, Bói B, Papp G, Fiák E, Gáspár-Kiss E, Perge B, Farmasi N, and Tarr T
- Abstract
In systemic lupus erythematosus (SLE), cardiovascular complications are among the leading causes of death. Cardiovascular risk in SLE is even higher in the presence of antiphospholipid antibodies or secondary antiphospholipid syndrome (APS). The aim of this retrospective, single-center study was to investigate the occurrence of antiphospholipid antibodies and non-thrombotic cardiac manifestations in 369 SLE patients. We also assessed the clinical and laboratory characteristics of the patients to reveal the risk factors for cardiac manifestations. Patients were divided into two groups based on the presence of antiphospholipid antibodies (APA); 258 (69.9%) patients were APA positive, and 111 (30.1%) patients were APA negative. Mitral and tricuspid insufficiency, aortic stenosis and pulmonary arterial hypertension were more common in APA-positive patients. Anticardiolipin IgG showed the strongest correlation with any non-thrombotic cardiac manifestations. Based on our results, the adjusted global antiphospholipid syndrome score (aGAPSS) above 8.5 is predictive of valvulopathies and ischemic heart disease, while aGAPSS above 9.5 is predictive of cardiomyopathies. The presence of antiphospholipid antibodies may affect the development of cardiac manifestations in SLE. Periodic cardiological and echocardiographic screening of patients without cardiac complaints, as well as regular monitoring of antiphospholipid antibodies, have great importance during the treatment of SLE patients.
- Published
- 2024
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69. A novel way to evaluate autoantibody interference in samples with mixed antinuclear antibody patterns in the HEp-2 cell based indirect immunofluorescence assay and comparison of conventional microscopic and computer-aided pattern recognition.
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Nagy G, Földesi R, Csípő I, Tarr T, Szűcs G, Szántó A, Bubán T, Szekanecz Z, Papp M, Kappelmayer J, and Antal-Szalmás P
- Subjects
- Humans, Autoantibodies, Fluorescent Antibody Technique, Indirect, Computers, Antibodies, Antinuclear, Autoimmune Diseases
- Abstract
Background: A major challenge of the HEp-2 cell-based indirect immunofluorescence (IIF) assays is the correct identification of the individual anti-nuclear antibodies (ANAs) if more than one is present in a sample. We created artificial mixes by pooling two different samples with a single autoantibody in different titers. Comparison of the expected and observed patterns and titers clarifies the interference between the two tested ANAs., Methods: Serum samples with a single homogeneous or speckled ANA pattern were serially diluted and mixed in 16 combinations, providing end-point titers of 1:5,120 to 1:80 for both patterns. These mixes were tested by a HEp-2 IIF assay and were evaluated by conventional evaluation, the EUROPattern (EPa) system and on-screen analysis., Results: Homogeneous pattern can alter the identification of the speckled pattern much more than vice versa, but both has an interfering effect on the other. The effect of the interfering on the tested pattern was higher if the titer of the former one was higher. The pattern recognition efficacy of conventional and the on-screen evaluation was similar and superior compared to the EPa analysis., Conclusions: The application of artificial mixed samples can help the evaluation of the efficacy of manual and computer-aided ANA HEp-2 pattern recognition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2024
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70. Psoriatic arthritis and its special features predispose not only for osteoporosis but also for fractures and falls.
- Author
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Halasi A, Szegedi A, Törőcsik D, Varga J, Farmasi N, Szűcs G, Tarr T, and Gaál J
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- Humans, Bone Density, Risk Factors, Arthritis, Psoriatic complications, Arthritis, Psoriatic epidemiology, Osteoporosis epidemiology, Osteoporosis complications, Fractures, Bone epidemiology, Fractures, Bone etiology, Psoriasis complications
- Abstract
Limited data are available on the predisposing factors to fractures and falls of patients with psoriatic arthritis (PsA). Our study intended to explore the differences between PsA patients and controls, concerning bone mineral density (BMD), the 10-year fracture risk, the number of prevalent fractures, the frequency of falls and to investigate the association of the same factors with PsA disease characteristics within the PsA group. Medical reports of 61 PsA patients and 69 consecutive, age-matched controls were analyzed, physical examination and bone mineral density (BMD, and T-score) were performed, and the 10-year fracture risk was calculated. The results were subjected to statistical analysis. Femoral neck BMD, as well as vertebral and femoral neck T-scores were lower, the odds ratio (OR) for low BMD and the 10-year risk of hip fracture was higher (p = 0.0029; 0.0002, p < 0.0001, OR = 21,9, p = 0.014) in the PsA group. The PsA patients were more predisposed to prevalent fractures, including peripheral fractures, and vertebral fractures as well as falls (OR 3.42; 2.26; 13.33; 3.95, respectively), compared to controls. Within the PsA group (beyond the age) scalp psoriasis and late-onset psoriasis, were significantly associated with a greater number of prevalent fractures (p = 0.0049; 0.029), while the number of falls per year correlated with late-onset psoriasis and the flexural psoriasis (p = 0.007; 0.023). Our results suggest that PsA is an independent risk factor for reduced bone density and falls hence to related bone fractures. Patients with late-onset psoriasis are more likely to suffer falls and related fractures, especially if their disease is characterized by the involvement of the hairy scalp and body folds., (© 2023 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)
- Published
- 2023
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71. Changes in Clinical Manifestations and Course of Systemic Lupus Erythematosus and Secondary Antiphospholipid Syndrome over Three Decades.
- Author
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Nagy N, Papp G, Gáspár-Kiss E, Diószegi Á, and Tarr T
- Abstract
Systemic lupus erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which potentially results in a more severe disease course and reduced life expectancy. Since the therapeutic guidelines have been refined in the last 15 years, we assumed that the diseases course has become more favorable. In order to shed light on these achievements, we compared the data of SLE patients diagnosed before and since 2004. In our retrospective study, we assessed a wide spectrum of clinical and laboratory data of 554 SLE patients who received regular follow-up care and therapy at our autoimmune center. Among these patients, 247 had antiphospholipid antibodies (APAs) without clinical signs of APS, and 113 had definitive APS. In the APS group, among patients diagnosed since 2004, deep vein thrombosis ( p = 0.049) and lupus anticoagulant positivity ( p = 0.045) were more frequent, while acute myocardial infarction was less frequent ( p = 0.021) compared with patients diagnosed before 2004. Among the APA positive patients without definitive APS, anti-cardiolipin antibody positivity ( p = 0.024) and development of chronic renal failure ( p = 0.005) decreased in patients diagnosed since 2004. Our study demonstrates that the disease course has changed in recent years; however, in the presence of APS, we have to expect repeated thrombotic events despite adequate anticoagulant therapy.
- Published
- 2023
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72. Role of Altered Metabolism of Triglyceride-Rich Lipoprotein Particles in the Development of Vascular Dysfunction in Systemic Lupus Erythematosus.
- Author
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Diószegi Á, Lőrincz H, Kaáli E, Soltész P, Perge B, Varga É, Harangi M, and Tarr T
- Subjects
- Humans, Pulse Wave Analysis, Lipoproteins, Triglycerides, Risk Factors, Carotid Intima-Media Thickness, Lupus Erythematosus, Systemic
- Abstract
Background: Impaired lipid metabolism contributes to accelerated inflammatory responses in addition to promoting the formation of atherosclerosis in systemic lupus erythematosus (SLE). We aimed to evaluate the lipid profile, inflammatory markers, and vascular diagnostic tests in active SLE patients to clarify the association between dyslipidemia and early vascular damage., Patients and Methods: 51 clinically active SLE patients and 41 age- and gender-matched control subjects were enrolled in the study. Lipoprotein subfractions were detected by Lipoprint. Brachial artery flow-mediated dilation and common carotid intima-media thickness were detected by ultrasonography. Arterial stiffness indicated by augmentation index (Aix) and pulse wave velocity was measured by arteriography., Results: We found significantly higher Aix, higher VLDL ratio, plasma triglyceride, ApoB100, and small HDL, as well as lower HDL-C, large HDL, and ApoA1 in patients with SLE. There was a significant positive correlation of Aix with triglyceride, VLDL, IDL-C, IDL-B, and LDL1. A backward stepwise multiple regression analysis showed IDL-C subfraction to be the best predictor of Aix., Conclusions: Our results indicate that in young patients with SLE, triglyceride-rich lipoproteins influence vascular function detected by Aix. These parameters may be assessed and integrated into the management plan for screening cardiovascular risk in patients with SLE.
- Published
- 2023
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73. The Effect of Aerobic Exercise and Low-Impact Pilates Workout on the Adaptive Immune System.
- Author
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Balogh L, Szabó K, Pucsok JM, Jámbor I, Gyetvai Á, Mile M, Barna L, Szodoray P, Tarr T, Csiki Z, and Papp G
- Abstract
Growing evidence indicates the pronounced effects of physical activity on immune functions, which may largely depend on the type of exercise, intensity, and duration. However, limited information is available regarding the effects of low-impact exercises, especially on the level of adaptive immune system. Our study aimed to investigate and compare the changes in a broad spectrum of lymphocyte subtypes after 14 weeks of aerobic-type total-body-shaping workouts (TBSW) and Pilates workouts (PW) among healthy individuals. We determined the percentages of peripheral natural killer cells and different T and B lymphocyte subtypes with flow cytometry. At the end of the exercise program, significant changes in naïve and memory lymphocyte ratios were observed in TBSW group. Percentages of naïve cytotoxic T (Tc) cells elevated, frequencies of memory Tc and T-helper cell subsets decreased, and distribution of naïve and memory B cells rearranged. Proportions of activated T cells also showed significant changes. Nonetheless, percentages of anti-inflammatory interleukin (IL)-10-producing regulatory type 1 cells and immunosuppressive CD4
+ CD127lo/- CD25bright T regulative cells decreased not only after TBSW but also after PW. Although weekly performed aerobic workouts may have a more pronounced impact on the adaptive immune system than low-impact exercises, both still affect immune regulation in healthy individuals.- Published
- 2022
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74. Altered Circulating Follicular T Helper Cell Subsets and Follicular T Regulatory Cells Are Indicators of a Derailed B Cell Response in Lupus, Which Could Be Modified by Targeting IL-21R.
- Author
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Szabó K, Jámbor I, Pázmándi K, Nagy N, Papp G, and Tarr T
- Subjects
- Humans, T-Lymphocytes, Helper-Inducer, T-Lymphocytes, Regulatory, Autoantibodies metabolism, Antibodies, Monoclonal metabolism, Complement C4 metabolism, Receptors, Interleukin-21 metabolism, Lupus Erythematosus, Systemic
- Abstract
Systemic lupus erythematosus (SLE) is characterized by the breakdown of self-tolerance, the production of high-affinity pathogenic autoantibodies and derailed B cell responses, which indicates the importance of central players, such as follicular T helper (T
FH ) subsets and follicular T regulatory (TFR ) cells, in the pathomechanism of the disease. In this study, we aimed to analyze the distribution of the circulating counterparts of these cells and their association with disease characteristics and B cell disproportions in SLE. We found that the increased percentage of activated circulating TFH (cTFH ) and cTFR cells was more pronounced in cutaneous lupus; however, among cTFH subsets, the frequency of cTFH 17 cells was decreased in patients with lupus nephritis. Furthermore, the decreased proportion of cTFH 17 cells was associated with low complement C4 levels and high disease activity scores. We also investigated whether the blocking of the IL-21 receptor (IL-21R) with an anti-IL-21R monoclonal antibody inhibits the B cell response, since IL-21 primarily produced by TFH cells potentially promotes humoral immunity. We observed that anti-IL-21R inhibited plasmablast generation and immunoglobulin production. Our study demonstrated that, besides cTFR /cTFH imbalance, cTFH 17 cells play a crucial role in SLE pathogenesis, and modulating cTFH -B cell interaction through the IL-21/IL-21R pathway may be a promising therapeutic strategy to suppress the pathological B cell response.- Published
- 2022
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75. Interactions between the NLRP3-Dependent IL-1β and the Type I Interferon Pathways in Human Plasmacytoid Dendritic Cells.
- Author
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Bencze D, Fekete T, Pfliegler W, Szöőr Á, Csoma E, Szántó A, Tarr T, Bácsi A, Kemény L, Veréb Z, and Pázmándi K
- Subjects
- Humans, NF-kappa B metabolism, Signal Transduction, Interleukin-1beta metabolism, Dendritic Cells, Interferon-alpha metabolism, Antiviral Agents metabolism, Interferon Regulatory Factors metabolism, Anti-Bacterial Agents metabolism, Nucleotides metabolism, Inflammasomes metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Interferon Type I metabolism
- Abstract
Generally, a reciprocal antagonistic interaction exists between the antiviral type I interferon (IFN) and the antibacterial nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3)-dependent IL-1β pathways that can significantly shape immune responses. Plasmacytoid dendritic cells (pDCs), as professional type I IFN-producing cells, are the major coordinators of antiviral immunity; however, their NLRP3-dependent IL-1β secretory pathway is poorly studied. Our aim was to determine the functional activity of the IL-1β pathway and its possible interaction with the type I IFN pathway in pDCs. We found that potent nuclear factor-kappa B (NF-κB) inducers promote higher levels of pro-IL-1β during priming compared to those activation signals, which mainly trigger interferon regulatory factor (IRF)-mediated type I IFN production. The generation of cleaved IL-1β requires certain secondary signals in pDCs and IFN-α or type I IFN-inducing viruses inhibit IL-1β production of pDCs, presumably by promoting the expression of various NLRP3 pathway inhibitors. In line with that, we detected significantly lower IL-1β production in pDCs of psoriasis patients with elevated IFN-α levels. Collectively, our results show that the NLRP3-dependent IL-1β secretory pathway is inducible in pDCs; however, it may only prevail under inflammatory conditions, in which the type I IFN pathway is not dominant.
- Published
- 2022
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76. The role of protein kinase C isoenzymes in the pathogenesis of human autoimmune diseases.
- Author
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Sipka S, Bíró T, Czifra G, Griger Z, Gergely P, Brugós B, and Tarr T
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- Female, Humans, Isoenzymes genetics, Leukocytes, Mononuclear metabolism, Protein Kinase C, Autoimmune Diseases etiology, Lupus Erythematosus, Systemic metabolism, Sjogren's Syndrome genetics
- Abstract
The physiological role of protein kinase C (PKC) enzymes in the immune system is presented briefly. From earlier publications of others data were collected how the defects of one/two isoenzymes of PKC system suggested their involvement in the pathogenesis of human autoimmune diseases. Our observations on the defects of seven PKC isoenzymes in the peripheral blood mononuclear cells (PBMC) demonstrate that these molecular impairments are not prerequisits of the pathogenesis of systemic lupus erythematosus (SLE), mixed connective tissue disease and Sjögren's syndrome. However, these defects can modulate the disease activity and symptoms especially in SLE by several pathways. The role of PKC system in other forms of autoimmune diseases is also very small. It was of note that we detected decreased expression of PKC isoenzymes in PBMC of a European white family with an X-linked genetic background showing seasonal undulations in the lupus patient and also in her healthy mother., (Copyright © 2022. Published by Elsevier Inc.)
- Published
- 2022
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77. A Comprehensive Investigation into the Distribution of Circulating B Cell Subsets in the Third Trimester of Pregnancy.
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Kövér Á, Lampé R, Szabó K, Tarr T, and Papp G
- Abstract
Maternal B cells play a crucial role in the development and maintenance of pregnancy, due to their humoral activities and regulatory functions. In the study, we investigated the alterations in the distributions of naïve and memory B cell subsets, as well as regulatory B (Breg) cells, in the third trimester of pregnancy. Peripheral blood from 14 healthy pregnant women in the third trimester and 7 healthy non-pregnant women was collected and examined for the frequencies of B cell subsets, including IgD
+ CD27- naïve, IgD+ CD27+ un-switched memory, IgD- CD27+ switched memory, CD38int CD24int mature-naïve, CD38- CD24hi primarily memory and CD38hi CD24hi transitional B cells by flow cytometry. Breg cell subsets were also characterized based on the expression of CD5, CD1d and IL-10. In pregnant women, the proportions of un-switched memory and transitional B cells were significantly decreased. Additionally, the frequencies of both CD5+ CD1d+ Breg and IL-10-producing B10 cells were decreased in pregnancy. Changes in the distribution of transitional B cells as well as Breg cells may be crucial contributors for the development of altered maternal immune responses and tolerance needed for the maintenance of normal pregnancy in the third trimester.- Published
- 2022
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78. A new medication, a new toxidrome - A case report of anticholinergic wipe toxicity due to improper medication use.
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Michael T and Paul C
- Subjects
- Administration, Topical, Adolescent, Axilla, Cholinergic Antagonists administration & dosage, Emergency Service, Hospital, Female, Glycopyrrolate administration & dosage, Hoarseness chemically induced, Humans, Hyperhidrosis drug therapy, Mydriasis chemically induced, Urinary Incontinence chemically induced, Cholinergic Antagonists toxicity, Glycopyrrolate toxicity
- Abstract
We describe a case of a young female who presented to the emergency department with 4 days of progressive myopia, dry mouth, anhidrosis and urinary hesitancy due to overuse of a new topical anticholinergic wipes, glycopyrronium tosylate (GT). In the United States medication misuse accounts for nearly 10% of pediatric emergency visits with 65% of these visits considered to be preventable [1]. Being familiar with new medications and their side effect profiles can prevent unnecessary or harmful interventions., Competing Interests: Declaration of Competing Interest The authors of this manuscript have no conflicts of interest and/or other potentially conflicting interests, including specific financial interests and relationships and affiliations., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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79. The Imbalance of Circulating Follicular T Helper Cell Subsets in Primary Sjögren's Syndrome Associates With Serological Alterations and Abnormal B-Cell Distribution.
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Szabó K, Jámbor I, Szántó A, Horváth IF, Tarr T, Nakken B, Szodoray P, and Papp G
- Subjects
- Adult, Aged, Autoantibodies immunology, CD40 Antigens immunology, Cell Differentiation immunology, Female, Flow Cytometry methods, Humans, Interleukins immunology, Male, Middle Aged, T-Lymphocytes, Regulatory immunology, B-Lymphocytes immunology, Sjogren's Syndrome immunology, T-Lymphocytes, Helper-Inducer immunology
- Abstract
Since B-cell hyperactivity and pathologic antibody response are key features in the immunopathogenesis of primary Sjögren's syndrome (pSS), the role of follicular T helper (T
FH ) cells as efficient helpers in the survival and differentiation of B cells has emerged. Our aim was to investigate whether a change in the balance of circulating (c)TFH subsets and follicular regulatory T (TFR ) cells could affect the distribution of B cells in pSS. Peripheral blood of 38 pSS patients and 27 healthy controls was assessed for the frequencies of cTFH cell subsets, TFR cells, and certain B cell subpopulations by multicolor flow cytometry. Serological parameters, including anti-SSA, anti-SSB autoantibodies, immunoglobulin, and immune complex titers were determined as part of the routine diagnostic evaluation. Patients with pSS showed a significant increase in activated cTFH cell proportions, which was associated with serological results. Frequencies of cTFH subsets were unchanged in pSS patients compared to healthy controls. The percentages and number of cTFR cells exhibited a significant increase in autoantibody positive patients compared to patients with seronegative pSS. The proportions of transitional and naïve B cells were significantly increased, whereas subsets of memory B cells were significantly decreased and correlated with autoantibody production. Functional analysis revealed that the simultaneous blockade of cTFH and B cell interaction with anti-IL-21 and anti-CD40 antibodies decreased the production of IgM and IgG. Imbalance in TFH subsets and TFR cells indicates an ongoing over-activated humoral immune response, which contributes to the characteristic serological manifestations and the pathogenesis of pSS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Szabó, Jámbor, Szántó, Horváth, Tarr, Nakken, Szodoray and Papp.)- Published
- 2021
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80. Anti-β 2 -glycoprotein I autoantibodies influence thrombin generation parameters via various mechanisms.
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Szabó G, Debreceni IB, Tarr T, Soltész P, Østerud B, and Kappelmayer J
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- Antibodies, Antiphospholipid, Autoantibodies, Female, Humans, Pregnancy, beta 2-Glycoprotein I, Antiphospholipid Syndrome, Thrombin
- Abstract
Introduction: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by recurrent thrombotic events, pregnancy loss and thrombocytopenia and the presence of antiphospholipid antibodies (APL). The exact pathomechanism of APS is still unknown, thus we investigated the effect of anti-β
2 -glycoprotein I (anti-β2 GPI) on thrombin generation in different plasma samples., Methods: For the separation of anti-β2 GPI IgG, overall 12 APS patients were selected. The criteria were the existence of lupus anticoagulant, and the presence of anti-CL and anti-β2 GPI, the latter exceeding at least 25 times the upper reference limit. We purified anti-β2 GPI IgG antibodies from APS patients by affinity chromatography and added the antibodies to normal pooled, and heterozygous forms of inherited thrombophilia plasma samples (prothrombin G20210A, factor V Leiden). To further specify the mechanism of the effect, we also used factor deficient plasmas in the thrombin generation assay., Results: In normal pooled plasma, the anti-β2 GPI significantly prolonged Lag Time according to the lupus anticoagulant effect, in contrast, it also elevated Peak Thrombin significantly, which suggests a procoagulant effect. The antibody was also able to exert this multi-faceted effect both in FVLeiden heterozygous plasma and prothrombin G20210A heterozygous polymorphism, however, the prolonging effect was more remarkable in the latter. By using factor deficient plasmas, it was found that FVII is required for the prolongation, while intrinsic factors are needed for the elevation of the Peak Thrombin., Conclusion: The anti-β2 GPI autoantibodies exert their effect in both normal and thrombophilic plasmas via various mechanisms., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2021
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81. Anti-neutrophil cytoplasmic antibody testing by indirect immunofluorescence: Computer-aided versus conventional microscopic evaluation of routine diagnostic samples from patients with vasculitis or other inflammatory diseases.
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Nagy G, Csípő I, Tarr T, Szűcs G, Szántó A, Bubán T, Sipeki N, Szekanecz Z, Papp M, Kappelmayer J, and Antal-Szalmás P
- Subjects
- Antibodies, Antinuclear, Computers, Fluorescent Antibody Technique, Indirect, Humans, Antibodies, Antineutrophil Cytoplasmic, Vasculitis diagnosis
- Abstract
Background: Detection of anti-neutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence assays (IFA) is of diagnostic importance in vasculitides and some other inflammatory diseases. Automation of IFA may be beneficial in high-throughput clinical laboratories. An analytical appraisal of the EUROPattern (EPa) automated microscope and image analysis system has not been reported in a routine clinical laboratory setting testing samples from both vasculitis and non-vasculitis patients., Methods: Results of EPa and on-screen ANCA pattern recognition of 568 consecutive routine serum samples were compared to those of conventional visual evaluation., Results: Agreement of discrimination between negative and non-negative samples was 86.1% comparing EPa and conventional reading, and it increased to 96.7% after on-screen user validation. Importantly, from the 334 samples classified as negative by EPa 328 (98.2%) were also negative by conventional evaluation. Pattern recognition showed 'moderate' agreement between classical microscopic and EPa analysis (κ = 0.446) and 'very good' agreement after user validation (κ = 0.900). Misclassification by EPa was dominantly due to the presence of anti-nuclear/cytoplasmic antibodies (incorrect pattern, 80/568) and the lower fluorescence cut-off of the automated microscope (false positives, 73/568)., Conclusions: Automated ANCA testing by EPa is a reliable alternative of classical microscopic evaluation, though classification of sera needs correction by trained personnel during on-screen validation., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
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82. Distinct and overlapping effects of β 2 -glycoprotein I conformational variants in ligand interactions and functional assays.
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Szabó G, Pénzes K, Torner B, Fagyas M, Tarr T, Soltész P, Kis G, Antal M, and Kappelmayer J
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- Anticoagulants pharmacology, Autoantibodies metabolism, Binding Sites, Antibody, Fibrin metabolism, Heparin pharmacology, Humans, Ligands, Partial Thromboplastin Time, Protein Conformation, Prothrombin Time, Structure-Activity Relationship, Thrombin metabolism, beta 2-Glycoprotein I antagonists & inhibitors, beta 2-Glycoprotein I chemistry, beta 2-Glycoprotein I immunology, Blood Coagulation drug effects, beta 2-Glycoprotein I metabolism
- Abstract
One of the most abundant coagulation proteins is β
2 -glycoprotein I (β2 GPI) that is present in humans at a concentration of around 200 mg/L. Its physiological role is only partially understood, but it adopts several different structural forms the majority of which are the open and closed forms. We isolated native (circular) β2 GPI and converted it into an open conformation. The effectiveness of these procedures was assessed by Western blot and negative-staining electron microscopy. We found that in coagulation assays the open form of β2 GPI had a significant prolonging effect on fibrin formation in a dilute prothrombin time test (p < 0.001). In the dilute activated partial thromboplastin time test, both conformations had a significant prolonging effect (p < 0.001) but the open conformation was more effective. In a fluorescent thrombin generation assay both conformations slightly delayed thrombin generation with no significant effect on the quantity of formed thrombin. By using surface plasmon resonance assays, the equilibrium dissociation constants of both the open and closed conformations of β2 GPI showed a similar and strong affinity to isolated anti-β2 GPI autoantibodies (Kd closed β2 GPI = 5.17 × 10-8 M, Kd open β2 GPI = 5.56 × 10-8 M) and the open form had one order of magnitude stronger affinity to heparin (Kd = 0.30 × 10-6 M) compared to the closed conformation (Kd = 3.50 × 10-6 M). The two different forms of β2 GPI have distinct effects in functional tests and in ligand binding, which may considerably affect the intravascular events related to this abundant plasma protein in health and disease., (Copyright © 2020. Published by Elsevier B.V.)- Published
- 2020
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83. Regulation of RLR-Mediated Antiviral Responses of Human Dendritic Cells by mTOR.
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Fekete T, Ágics B, Bencze D, Bene K, Szántó A, Tarr T, Veréb Z, Bácsi A, and Pázmándi K
- Subjects
- Antineoplastic Agents pharmacology, Cell Differentiation, Cell Line, Cell Proliferation, Cells, Cultured, Humans, Interferon Type I metabolism, Mechanistic Target of Rapamycin Complex 1 metabolism, Morpholines pharmacology, Protein Serine-Threonine Kinases metabolism, Signal Transduction, CD8-Positive T-Lymphocytes immunology, DEAD Box Protein 58 metabolism, Dendritic Cells immunology, Monocytes immunology, Receptors, Immunologic metabolism, TOR Serine-Threonine Kinases metabolism, Vaccines immunology, Virus Diseases immunology
- Abstract
To detect replicating viruses, dendritic cells (DCs) utilize cytoplasmic retinoic acid inducible gene-(RIG) I-like receptors (RLRs), which play an essential role in the subsequent activation of antiviral immune responses. In this study, we aimed to explore the role of the mammalian target of rapamycin (mTOR) in the regulation of RLR-triggered effector functions of human monocyte-derived DCs (moDCs) and plasmacytoid DCs (pDCs). Our results show that RLR stimulation increased the phosphorylation of the mTOR complex (mTORC) 1 and mTORC2 downstream targets p70S6 kinase and Akt, respectively, and this process was prevented by the mTORC1 inhibitor rapamycin as well as the dual mTORC1/C2 kinase inhibitor AZD8055 in both DC subtypes. Furthermore, inhibition of mTOR in moDCs impaired the RLR stimulation-triggered glycolytic switch, which was reflected by the inhibition of lactate production and downregulation of key glycolytic genes. Blockade of mTOR diminished the ability of RLR-stimulated moDCs and pDCs to secret type I interferons (IFNs) and pro-inflammatory cytokines, while it did not affect the phenotype of DCs. We also found that mTOR blockade decreased the phosphorylation of Tank-binding kinase 1 (TBK1), which mediates RLR-driven cytokine production. In addition, rapamycin abrogated the ability of both DC subtypes to promote the proliferation and differentiation of IFN-y and Granzyme B producing CD8 + T cells. Interestingly, AZD8055 was much weaker in its ability to decrease the T cell proliferation capacity of DCs and was unable to inhibit the DC-triggered production of IFN-y and Granyzme B by CD8 + T cells. Here we demonstrated for the first time that mTOR positively regulates the RLR-mediated antiviral activity of human DCs. Further, we show that only selective inhibition of mTORC1 but not dual mTORC1/C2 blockade suppresses effectively the T cell stimulatory capacity of DCs that should be considered in the development of new generation mTOR inhibitors and in the improvement of DC-based vaccines., (Copyright © 2020 Fekete, Ágics, Bencze, Bene, Szántó, Tarr, Veréb, Bácsi and Pázmándi.)
- Published
- 2020
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84. Antiphospholipid syndrome and the risk of myocardial infarction: current evidence and uncertainties.
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Lóczi L, Kappelmayer J, Tarr T, and Bagoly Z
- Subjects
- Antibodies, Antiphospholipid, Anticoagulants therapeutic use, Female, Humans, Pregnancy, Antiphospholipid Syndrome complications, Myocardial Infarction epidemiology, Myocardial Infarction etiology, Thrombosis etiology
- Abstract
Antiphospholipid syndrome (APS) encompasses a wide spectrum of disease manifestations that may prevail in the form of venous or arterial thrombosis or lead to pregnancy complications in the presence of persisting antiphospholipid antibodies (aPL). Unlike in the case of congenital thrombophilias, in which venous thromboses are more likely to occur as compared with arterial events, aPL may cause thrombosis in both types of vascular systems. Arterial thrombosis in APS is fairly common and often involve coronary or cerebral arteries leading to myocardial infarction (MI) or stroke. In this review, we summarize the complex pathomechanisms leading to aPL‑associated thrombosis and list challenges during the laboratory detection of these antibodies. Specific features of MI in patients with APS are summarized based on a comprehensive literature search of available case reports. Preventive and treatment strategies are discussed based on the current recommendations and most recent evidence. We conclude that the risk of MI in patients with APS is considerable and MI may be the first manifestation of the disease. MI in APS shows specific clinical features including relatively young age at presentation, no sex dominance, often normal coronaries without the sign of atherosclerosis, high risk of recurrent thrombotic events. Treatment of acute MI in patients with APS is often challenging and adverse events, including stent thrombosis, are more frequent as compared with patients without APS. Preventive strategies in APS should be personalized and include strict management of additional cardiovascular risk factors and long‑term anticoagulation with vitamin K antagonists. Current evidence does not support the use of direct oral anticoagulants in the management of patients with APS with arterial thrombosis due to the high risk of recurrent events.
- Published
- 2020
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85. Season Dependent Changes in the Expression of Protein Kinase C Isoenzymes in a Female Patient with Systemic Lupus Erythematosus.
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Sipka S, Brugós B, Czifra G, Griger Z, Balogh N, Tarr T, Papp G, Bíró T, and Zeher M
- Subjects
- Child, Female, Humans, Isoenzymes blood, Leukocytes, Mononuclear enzymology, Seasons, Young Adult, Lupus Erythematosus, Systemic blood, Lupus Erythematosus, Systemic enzymology, Protein Kinase C blood
- Abstract
We aimed to answer the question whether the decreased expression of protein kinase C (PKC) isoenzymes in the peripheral blood mononuclear cells (PBMC) of patients with systemic lupus erythematosus (SLE) is inherited or not. For this reason we examined the expression of PKC isoenzymes in a European white girl with acute SLE and in her healthy mother and father simultaneously in summer and winter during one year using western blotting and densitometry. We found that in the father the expression of PKC isoenzymes did not differ from that of eight healthy controls included women and men. However, in the "SLE-free" mother and in the patient arrived in July with acute symptoms of lupus, the expression of PKC isoenzymes showed a season dependent undulation in parallel. Namely, in summer the expression values were significantly lower, in winter they were significantly higher than those in the controls. Thus, the decreased expression of PKC isoenzymes in the PBMC of SLE patient is not a disease specific marker; it appears also in her lupus free mother. This phenomenon may be due to a season dependent female genetic background. However, the low PKC levels in summer can still decrease further the low production of IL-2 in T cells of lupus patients augmenting the existing AP-1 defects. This is the first report on the season and female dependent inherited changing of PKC expression in a European white patient with SLE and her mother. Further studies are needed to confirm these findings in other populations.
- Published
- 2019
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86. Elemental Analysis of Whole and Protein Separated Blood Serum of Patients with Systemic Lupus Erythematosus and Sjögren's Syndrome.
- Author
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Tóth CN, Baranyai E, Csípő I, Tarr T, Zeher M, Posta J, and Fábián I
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Blood Proteins isolation & purification, Lupus Erythematosus, Systemic blood, Sjogren's Syndrome blood, Trace Elements blood
- Abstract
Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are systemic autoimmune diseases with complex symptoms and pathogenesis that are still not completely understood. Several studies showed that the trace element homeostasis and also the levels of antioxidant plasma proteins are changed in autoimmune disorders; however, these results are controversial. In this study, the potassium (K), calcium (Ca), magnesium (Mg), copper (Cu), zinc (Zn), and iron (Fe) concentrations of the serum and proteins-immunoglobulin G (IgG), transferrin (Trf), albumin (Alb), and ceruloplasmin (Cp)-separated from serum samples by affinity chromatography were determined in patients with SLE and SS. Ca and K levels were found to be decreased in the case of both disorders compared to the control group, and the competitive antagonism of Cu and Zn was also observed: elevated Cu concentration together with a lower Zn concentration was measured in the sera of patients with autoimmune diseases. After fractionation, the trace element concentration of protein containing fractions altered to that of the control group. In case of the autoimmune disorders, the highest Cu concentration was determined in the Alb-containing protein fractions while the Zn level decreased in the Alb and increased in the Cp as well as in the IgG- and Trf-containing fractions compared to the healthy samples. Changes have also been found in the level and distribution of K and Ca.
- Published
- 2017
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87. MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren's syndrome.
- Author
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Chen JQ, Papp G, Póliska S, Szabó K, Tarr T, Bálint BL, Szodoray P, and Zeher M
- Subjects
- Adult, Aged, B-Lymphocytes metabolism, Female, Gene Expression Profiling, Humans, Leukocytes, Mononuclear metabolism, Lupus Erythematosus, Systemic metabolism, MicroRNAs metabolism, Middle Aged, Sjogren's Syndrome metabolism, Gene Expression Regulation, Lupus Erythematosus, Systemic genetics, MicroRNAs genetics, Sjogren's Syndrome genetics
- Abstract
The discovery of microRNAs (miRNAs) and their critical role in genetic control opened new avenues in understanding of various biological processes including immune cell lineage commitment, differentiation, proliferation and apoptosis. However, a given miRNA may have hundreds of different mRNA targets and a target might be regulated by multiple miRNAs, thus the characterisation of dysregulated miRNA expression profiles could give a better insight into the development of immunological disturbances in autoimmune diseases. The aim of our study was to examine the changes in miRNA expression profiles in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). Eight SLE patients, 8 pSS patients and 7 healthy subjects were enrolled in the investigation. MiRNAs were isolated from peripheral blood mononuclear cells, and expression patterns were determined with Illumina next-generation sequencing technology. Since the immunopathogenesis of pSS and SLE encompasses pronounced B cell hyperactivity along with specific autoantibody production, we paid a special attention on the association between miRNA expression levels and altered peripheral B cell distribution. In SLE patients 135, while in pSS patients 26 miRNAs showed altered expression. Interestingly, the 25 miRNAs including miR-146a, miR-16 and miR-21, which were over-expressed in pSS patients, were found to be elevated in SLE group, as well. On the contrary, we observed the down-regulation of miR-150-5p, which is a novel and unique finding in pSS. Levels of several miRNAs over-expressed in SLE, were not changed in pSS, such as miR-148a-3p, miR-152, miR-155, miR-223, miR-224, miR-326 and miR-342. Expression levels of miR-223-5p, miR-150-5p, miR-155-5p and miR-342-3p, which miRNAs are potentially linked to B cell functions, showed associations with the B cell proportions within peripheral blood mononuclear cells. The observed differences in miRNA expression profiles and the better understanding of immune regulatory mechanisms of miRNAs may help to elucidate the pathogenesis of SLE and pSS.
- Published
- 2017
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88. Chronic high-dose glucocorticoid therapy triggers the development of chronic organ damage and worsens disease outcome in systemic lupus erythematosus.
- Author
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Tarr T, Papp G, Nagy N, Cserép E, and Zeher M
- Subjects
- Adult, Aged, Aged, 80 and over, Cardiovascular Diseases complications, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic mortality, Male, Middle Aged, Nervous System Diseases complications, Rheumatology methods, Time Factors, Treatment Outcome, Young Adult, Cardiovascular Diseases chemically induced, Glucocorticoids adverse effects, Glucocorticoids therapeutic use, Lupus Erythematosus, Systemic drug therapy, Nervous System Diseases chemically induced
- Abstract
Long-term survival of patients with systemic lupus erythematosus (SLE) improved worldwide; thus, prevention of cumulative organ damage became a major goal in disease management. The aim of our study was to investigate the chronic organ damages and their influence on disease outcome in SLE. We evaluated clinical conditions, laboratory findings and medications of 357 consecutive SLE patients and assessed their impact on Systemic Lupus Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) and disease outcome. We detected one or more SDI scores in 77.87% of patients. Patients with disease duration of more than 10 years and subjects diagnosed at age above 40 had significantly higher SDI values. The most frequent damages were valvulopathies, cognitive dysfunction, angina pectoris and venous thrombosis. Higher cumulative glucocorticoid dose increased SDI, while chloroquin treatment was favourable for patients. Male gender, elevated SDI scores and higher cumulative doses of glucocorticoids increased mortality risk. Our data confirmed that disease duration, age at diagnosis and chronic high-dose glucocorticoid therapy have significant effects on the development of chronic organ damage. Higher SDI score is characterized with worse survival ratios. The most common chronic organ damages affected the cardiovascular or neuropsychiatric system. As long-term survival in SLE improves, it becomes increasingly important to identify the determinants of chronic organ damage. Most of the chronic organ damage occurs in the cardiovascular and the neuropsychiatric systems; thus, regular follow-up, screening and adequate therapy are essential for the best clinical outcome.
- Published
- 2017
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89. High-density lipopoprotein antioxidant capacity, subpopulation distribution and paraoxonase-1 activity in patients with systemic lupus erythematosus.
- Author
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Gaál K, Tarr T, Lőrincz H, Borbás V, Seres I, Harangi M, Fülöp P, and Paragh G
- Subjects
- Adult, Apolipoprotein A-I blood, Aryldialkylphosphatase metabolism, Biomarkers blood, Biomarkers metabolism, Case-Control Studies, Cholesterol, HDL blood, Female, Humans, Inflammation blood, Inflammation metabolism, Interleukin-6 blood, Lipoproteins, HDL metabolism, Lupus Erythematosus, Systemic blood, Male, Oxidative Stress, Antioxidants metabolism, Aryldialkylphosphatase blood, Lipoproteins, HDL blood, Lupus Erythematosus, Systemic metabolism
- Abstract
Background: The causes of increased cardiovascular risk in systemic lupus erythematosus (SLE) are not understood thoroughly, although presence of traditional cardiovascular risk factors and disease-specific agents were also proposed. In this study, we investigated the quantitative changes in the lipid profile, as well as qualitative characteristics of high-density lipoprotein (HDL) and markers of inflammation and disease activity in SLE patients., Methods: Lipoprotein levels were determined in 51 SLE patients and 49 healthy controls, matched in age and gender. HDL antioxidant capacity was determined spectrophotometrically with a cell-free method of hemin-induced low-density lipoprotein (LDL) oxidation. Polyacrylamide gel-electrophoresis was used for HDL subfraction analysis. Human paraoxonase-1 (PON1) activity, apolipoprotein A1 (ApoA1) and oxidized LDL concentrations, as well as interleukin-6, high-sensitivity C-reactive protein, serum amyloid A and monocyte chemotactic protein-1 levels were determined., Results: HDL-cholesterol and ApoA1 concentrations decreased significantly in SLE subjects. Also, PON1 arylesterase activity (125.65 ± 26.87 vs. 148.35 ± 39.34 U/L, p = 0.001) and total HDL antioxidant capacity (165.82 ± 58.28% vs. 217.71 ± 54.36%, p < 0.001) were significantly reduced in patients compared to controls. Additionally, all HDL subfraction concentrations were significantly decreased in patients, while the levels of the examined inflammatory markers were significantly elevated in SLE subjects. The latter correlated positively with disease activity, and negatively with HDL concentration and total HDL antioxidant capacity, respectively. PON1 arylesterase activity and erythrocyte sedimentation rate were independent predictors of total HDL antioxidant capacity., Conclusions: Induced by the systemic inflammation, altered composition and antioxidant activity may diminish the anti-atherogenic effect of HDL and therefore may contribute to the increased cardiovascular risk of SLE patients.
- Published
- 2016
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90. Use of cyclophosphamide and other immunosuppressive drugs in the treatment of patients with lupus nephritis.
- Author
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Brugos B, Sebestyen L, Tarr T, and Vincze Z
- Subjects
- Adult, C-Reactive Protein analysis, Cohort Studies, Creatinine urine, DNA analysis, Disease Progression, Female, Humans, Lupus Nephritis complications, Lupus Nephritis pathology, Male, Renal Insufficiency etiology, Renal Insufficiency prevention & control, Skin pathology, Uridine Triphosphate urine, Cyclophosphamide therapeutic use, Immunosuppressive Agents therapeutic use, Lupus Nephritis drug therapy
- Abstract
Unlabelled: Systemic lupus erythematosus (SLE) is a chronic relapsing systemic autoimmune disease; one of the most serious complications is renal involvement, which is occurring in almost 50% of all patients at the beginning of the disease. The aim of the present study was to compare renal function, proteinuria, activity markers and treatment regimen of active and inactive SLE patients with renal involvement. We analyzed the correlation of serum blood urea nitrogen, creatinine level, glomerular filtration rate, urine total protein/serum creatinine (uTP/creat), CRP to classic activity markers of SLE (serum complement 3, -4 level, anti-dsDNA antibody). Moreover we analyzed the treatment modalities of patients with lupus nephritis (LN). Data of 418 SLE patients were analyzed, out of these patients 128 had biopsy proven lupus nephritis or had more than 3 + proteinuria by urine dipstick analysis (30% of all cases)., Results: Data of 128 patients with lupus nephritis were analyzed (mean age 32.18 +/- 11.48 year, time between the diagnosis of SLE and LN was 2.78 +/- 4.59 year). 48% of patients had diffuse proliferative glomerulonephritis, 75% of them received cyclic cyclophosphamide treatment. UTp (total protein)/creatinine level was significantly higher in active LN group (p = 0.03), and correlated to erythrocyte sedimentation rate (p = 0.002, R = 0.52). Mean anti-dsDNA level of patients with active LN was significantly higher (p < 0.001)., Conclusions: Patients with active lupus nephritis are at higher risk of developing renal failure, activity markers and urine protein are elevated in these patients as compared to inactive patients, early aggressive immunosuppressive treatment needs to be started to prevent end-stage renal failure.
- Published
- 2014
91. The in vitro treatment with vitamin D3 is ineffective on the expression of PKC isoenzymes, but decreases further the impaired production of IL-2 in the T lymphocytes of SLE patients.
- Author
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Czifra G, Tóth B, Kovács I, Bíró T, Griger Z, Baráth S, Tarr T, Zeher M, and Sipka S
- Subjects
- Adult, Aged, Case-Control Studies, Cells, Cultured, Dose-Response Relationship, Drug, Down-Regulation, Female, Humans, Isoenzymes, Male, Middle Aged, Signal Transduction, T-Lymphocytes enzymology, T-Lymphocytes immunology, Anti-Inflammatory Agents pharmacology, Calcitriol pharmacology, Interleukin-2 metabolism, Lupus Erythematosus, Systemic enzymology, Lupus Erythematosus, Systemic immunology, Protein Kinase C metabolism, T-Lymphocytes drug effects
- Abstract
The objective of the study was to investigate the possibility whether the in vitro treatment with vitamin D3 can restore the impaired expression of protein kinase C (PKC) isoenzymes and IL-2 production in the lymphocytes of patients with systemic lupus erythematosus (SLE). Purified T lymphocytes from 14 patients with SLE and 13 healthy controls were cultured for 48 h in the presence and absence of 1 and 100 nM doses of vitamin D3. The expressions of various PKC isoenzymes were tested by Western blot analysis, and the amounts of various cytokines were detected by ELISA in the culture supernatants. Neither the low (1 nM) nor the high (100 nM) doses of vitamin D3 (1α,-25-dihydroxyvitamin) applied in vitro for 48 h were able to restore the decreased expression of PKC isoenzymes in the T cells of SLE patients. However, 100 nM of vitamin D3 significantly increased the release of IL-10, but suppressed the production of IL-2, IL-6, interferon γ and TNF α in the culture supernatants of both groups. As the low production of IL-2 is one of the main pathologic features of SLE, we recommend to avoid the use of high doses of vitamin D3 for treatment of lupus patients with vitamin D3 deficiency.
- Published
- 2014
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92. [Successful completed pregnancies in patients with systemic lupus erythematosus].
- Author
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Tarr T, Kiss E, Szegedi G, and Zeher M
- Subjects
- Adrenal Cortex Hormones administration & dosage, Adult, Aspirin administration & dosage, Azathioprine administration & dosage, Birth Weight, Female, Follow-Up Studies, Gestational Age, Heparin, Low-Molecular-Weight administration & dosage, Humans, Immunoglobulins, Intravenous administration & dosage, Pregnancy, Pregnancy Complications therapy, Immunosuppressive Agents administration & dosage, Live Birth, Lupus Erythematosus, Systemic drug therapy, Pregnancy Complications immunology
- Abstract
Unlabelled: Systemic lupus erythematosus is a chronic autoimmune disorder which affects women with child bearing potential., Aim: The aim of this study was to investigate the successful pregnancies in patients with lupus in the past 10 years. Women were followed up at the 3rd Department of Internal Medicine, University of Debrecen., Results: During this investigated period, 26 patients became pregnant. Seven patients had a positive history for lupus before the pregnancy. A total of 29 children were born. The mean gestational age was 35 weeks. The average birth weight was 2415 grams. Toxemic pregnancy was the most common complication found in 9 patients. Lupus nephritis activity occurred in 2 patients, and 1 of them had it for the first time during the course of her disease., Conclusions: In the past years, the number of pregnancies in patients with lupus has been increasing. Due to proper patient care and education, the outcome is more favourable.
- Published
- 2012
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93. Increased microRNA-146a/b, TRAF6 gene and decreased IRAK1 gene expressions in the peripheral mononuclear cells of patients with Sjögren's syndrome.
- Author
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Zilahi E, Tarr T, Papp G, Griger Z, Sipka S, and Zeher M
- Subjects
- Aged, Biomarkers metabolism, Female, Gene Expression Regulation, Humans, Immunity, Innate, Interleukin-1 Receptor-Associated Kinases genetics, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear pathology, Male, MicroRNAs genetics, Middle Aged, Signal Transduction, Sjogren's Syndrome diagnosis, Sjogren's Syndrome genetics, TNF Receptor-Associated Factor 6 genetics, Interleukin-1 Receptor-Associated Kinases metabolism, Leukocytes, Mononuclear metabolism, MicroRNAs metabolism, Sjogren's Syndrome immunology, TNF Receptor-Associated Factor 6 metabolism
- Abstract
MicroRNA-146a (miR-146a) is a microRNA supposed to regulate innate immune, inflammatory response and antiviral pathway negatively. Recently, its potential use as a biomarker for disease diagnosis, prevention and treatment has become widely investigated. In the current study, we measured the expression of miR-146a/b, and their target genes, IRAK1, IRAK4, TRAF6 in the peripheral mononuclear cells of patients with Sjögren's syndrome (n=21) and healthy controls (n=10) by quantitative reverse transcription polymerase chain reaction. We found that both miR-146a and miR-146b, furthermore, the gene of TRAF6 were significantly overexpressed in the Sjögren's patients, whereas the expression of IRAK1 gene was significantly decreased. The expression of IRAK4 did not differ significantly. These results suggest that in the peripheral mononuclear cells of Sjögren's patients, the transcriptional repression of IRAK1 is taking place, whereas the other NF-κB pathway regulating gene, TRAF6 is overexpressed. As IRAK1 has been regarded a crucial gene in the pathogenesis of systemic lupus erythematosus, TRAF6 can be a Sjögren's syndrome specific biomarker, confirming and partly explaining the existance of different pathogenic pathways in the two diseases. These observations, however, need still wider confirmations., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2012
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94. Fatal CMV-Infection after Autologous Stem Cell Transplantation in Refractory Systemic Lupus Erythematosus.
- Author
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Váróczy L, Kiss E, Tarr T, Zeher M, Szegedi G, and Illés A
- Abstract
High-dose chemotherapy followed by autologous stem cell transplantation can be a rescue for patients with severe refractory systemic lupus erythematosus (SLE). However, the procedure might have fatal complications including infections and bleeding. We report on a young female patient with SLE whose disease started in her early childhood. After many years, severe renal, neurological, and bone marrow involvement developed that did not respond to conventional therapy. She was selected for autologous stem cell transplantation. A successful peripheral stem cell apheresis was performed in March 2006. The nonselected graft was reinfused in August 2006 after a conditioning chemotherapy containing high-dose cyclophosphamide and antithymocyte globulin. Engraftment was detected within 11 days. On the 38th posttransplant day, severe cytomegalovirus (CMV) infection developed that included pneumonitis, hepatitis, and pancytopenia. The patient died in a week due to multiorgan failure. With her case, we want to call the attention to this rare, but lethal complication of the autologous transplantation.
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- 2012
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95. Interleukin-23 receptor gene variants in Hungarian systemic lupus erythematosus patients.
- Author
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Safrany E, Hobor R, Jakab L, Tarr T, Csongei V, Jaromi L, Sipeky C, Valasek A, Zeher M, Fust G, Czirjak L, and Melegh B
- Subjects
- Adult, Alleles, Case-Control Studies, Gene Frequency genetics, Genetic Predisposition to Disease genetics, Genotype, Haplotypes genetics, Humans, Hungary, Middle Aged, Lupus Erythematosus, Systemic ethnology, Lupus Erythematosus, Systemic genetics, Polymorphism, Single Nucleotide genetics, Receptors, Interleukin genetics
- Abstract
Objective: We investigated the association between systemic lupus erythematosus (SLE) and polymorphisms of interleukin-23 receptor (IL23R) gene, which was recently found to be associated with autoimmune diseases, including Crohn's disease, rheumatoid arthritis, psoriasis and ankylosing spondylitis., Subjects: We analysed 383 SLE patients and 253 controls for rs11805303, rs10889677, rs1004819, rs2201841, rs11209032, 11209026, rs10489629, rs7517847 and rs7530511 variants., Methods: The analysis was carried out using PCR-RFLP methods. Logistic regression analysis was used to compare the genotype distributions of the polymorphisms and haplotypes between the SLE patients and healthy controls., Results: We observed no significant difference of the examined variants between the patient and control groups., Conclusions: Our results suggest that neither single nucleotide variants nor haplotypes of IL23R indicate susceptibility to developing SLE in the Hungarian population.
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- 2010
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96. Human leukocyte antigen-DRB1 and -DQB1 genotyping in lupus patients with and without antiphospholipid syndrome.
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Kapitany A, Tarr T, Gyetvai A, Szodoray P, Tumpek J, Poor G, Szegedi G, Sipka S, and Kiss E
- Subjects
- Alleles, Antibodies, Anticardiolipin blood, Antiphospholipid Syndrome complications, Antiphospholipid Syndrome immunology, Autoantibodies blood, Female, Gene Frequency, Genotype, HLA-DQ beta-Chains, HLA-DRB1 Chains, Humans, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic immunology, Male, Retrospective Studies, beta 2-Glycoprotein I immunology, Antiphospholipid Syndrome genetics, HLA-DQ Antigens genetics, HLA-DR Antigens genetics, Lupus Erythematosus, Systemic genetics
- Abstract
We investigated the genetic background regarding major histocompatibility complex (MHC) II alleles in patients with systemic lupus erythematosus (SLE) only, in patients with SLE with secondary antiphospholipid syndrome (SLE+SAPS), and in patients whose clinical course began as primary antiphospholipid syndrome (PAPS) and subsequently progressed to SLE (PAPS+SLE) in order to explain the phenotypical differences found in our previous study. Those with primary or secondary APS present more thrombotic and less inflammatory activity. Fetal wastage was the highest in the PAPS+SLE group. We performed human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 genotyping in 63 patients (26, 22, and 15 in SLE only, SLE+SAPS, and PAPS+SLE groups, respectively) and in 57 healthy controls, using PCR with sequence-specific primers. We found that, as reported in the literature, the occurrence of DRB1*03 and DQB1*0201 alleles was higher in SLE patients than in controls, but these alleles were rare in the PAPS+SLE group (13% in PAPS+SLE vs. 46% in the SLE only group; P = 0.044). HLA-DRB1*04 alleles were expressed frequently in both primary and secondary APS. DRB1*13, DQB1*06, and DQB1*0302 alleles were present more frequently in the PAPS+SLE patients than in the other groups, while the DQB1*0301 allele was rare. In this study we have shown that the SLE-associated DRB1*03/DQB1*02 alleles occurred frequently in our lupus patients as well as in SLE patients with secondary APS. In patients who started as PAPS and later progressed to SLE, the allele frequency was fundamentally different. Taken together, our results confirmed that the HLA-DRB1 and HLA-DQB1 profile of PAPS and SAPS is different. Therefore it is unlikely that these alleles are responsible for the partly similar phenotype of the two groups.
- Published
- 2009
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97. Identification of rare anti-phospholipid/protein co-factor autoantibodies in patients with systemic lupus erythematosus.
- Author
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Szodoray P, Tarr T, Tumpek J, Kappelmayer J, Lakos G, Poor G, Szegedi G, and Kiss E
- Subjects
- Adult, Annexin A5 immunology, Antibodies, Anticardiolipin blood, Antibodies, Anticardiolipin immunology, Antibodies, Antiphospholipid immunology, Antiphospholipid Syndrome complications, Antiphospholipid Syndrome diagnosis, Antiphospholipid Syndrome immunology, Autoantibodies immunology, Autoimmune Diseases complications, Autoimmune Diseases diagnosis, Autoimmune Diseases immunology, Female, Humans, Lupus Coagulation Inhibitor immunology, Male, Middle Aged, Phosphatidylserines immunology, Prothrombin immunology, Thrombosis complications, Thrombosis immunology, Antibodies, Antiphospholipid blood, Autoantibodies blood, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic diagnosis, Lupus Erythematosus, Systemic immunology
- Abstract
Lupus anticoagulant (LA) and beta2-glikoprotein I (b2GPI) dependent anti-cardiolipin (aCL) are part of the diagnostic criteria both of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). Anti-phospholipid antibodies (aPL) may also bind to other phospholipids and/or protein co-factors. In the present study, besides aCL and anti-b2GPI, antibodies directed against phosphatidylserine, prothrombin (PT) and annexin V (aANX) were measured in 85 randomly selected SLE patients, 14 suffering from secondary APS. LA was detected by hemostasis tests. Correlations were determined between rare aPLs and clinical manifestations, including thrombotic events. Anti-cardiolipin IgG was positive in 14 patients, aCL IgM in 8, anti-b2GPI IgG in 4 and IgM in 5 patients. LA was detected in nine cases. Seven patients were positive for anti-phosphatidylserine (aPS) IgG, nine for aPS IgM, while anti-PT (aPT) IgG was positive in nine cases. aPT IgM and anti-aANX were negative in all patients. Correlation was found between aPS and aCL antibodies. The frequency and concentration of rare anti-phospholipid/co-factor antibodies was higher in patients with secondary APS. The presence of such rare aPLs cumulated in APS patients, their presence increased the frequency of thrombotic events in the entire study population, furthermore in patients positive for LA or aCL. Rare anti-phospholipid/co-factor antibodies were found in 12% of an un-selected lupus patient population. Their presence was more frequent in patients with secondary APS, and further increased the risk of thrombotic complications.
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- 2009
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98. Tumor-associated antigens in systemic sclerosis and systemic lupus erythematosus: associations with organ manifestations, immunolaboratory markers and disease activity indices.
- Author
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Szekanecz E, Szucs G, Szekanecz Z, Tarr T, Antal-Szalmás P, Szamosi S, Szántó J, and Kiss E
- Subjects
- Adult, Aged, Antigens, Tumor-Associated, Carbohydrate immunology, Female, Humans, Lupus Erythematosus, Systemic blood, Male, Middle Aged, Scleroderma, Systemic blood, Antigens, Tumor-Associated, Carbohydrate blood, Lupus Erythematosus, Systemic immunology, Scleroderma, Systemic immunology
- Abstract
Background: Some tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected increased production of CA15-3, CA19-9 and CA125 in rheumatoid arthritis (RA). The production of some TAAs may also be increased in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and other connective tissue diseases. Some of these TAAs contain sialylated carbohydrate motifs and they are involved in tumor-associated cell adhesion and metastasis., Objectives: We assessed levels of TAAs in the sera of SSc, SLE patients, patients with infectious diseases and healthy subjects. Serum TAA levels were correlated with each other, as well as with disease activity markers and organ involvement., Methods: TAAs including CEA, CA15-3, CA72-4, CA125 and CA19-9 were assessed by immunoassay in the sera of 92 patients with SSc, 40 patients with SLE, 50 age- and sex-matched healthy controls, as well as with 40 patients with current bacterial or viral infections. Normal upper limits for these TAAs were 3.4 mg/l, 25 kU/l, 6.9 kU/l, 35 kU/l and 34 kU/l, respectively., Results: There were significantly more SSc patients showing abnormally high levels of CA19-9 (8.8% vs 2.0%), CA125 (11.0% vs 6.0%) and CA15-3 (28.4% vs 14.0%) in comparison to controls (p < 0.05). In SLE, significantly more patients had elevated levels of CEA (32.5% vs 20.0%), CA19-9 (7.5% vs 2.0%), CA125 (15.0% vs 6.0%) and CA72-4 (15.0% vs 8.0%) than did controls (p < 0.05). The mean absolute serum levels of CEA (6.6+/-1.7 vs 1.8+/-1.4 mg/l) and CA15-3 (22.9 +/- 1.8 vs 18.6 +/- 2.2 kU/l) were also significantly higher in SSc compared to controls (p < 0.05). We found numerous correlations between the serum levels of different TAAs within the SSc and SLE population. Among SSc patients, serum CEA (R = 0.290; p = 0.005), CA15-3 (R = 0.260; p = 0.020) and CA19-9 (R = 0.257; p = 0.013) correlated with renal involvement. Serum CA15-3 also correlated with joint involvement (R = 0.329; p = 0.003), ANA positivity (R = 0.288; p = 0.010) and CRP levels (R = 0.407; p < 0.001). Within the SLE population, serum CA72-4 correlated with central nervous involvement (R = 0.624; p = 0.004) and CA125 correlated with the SLEDAI composite activity index (R = 0.666; p = 0.002). Patients with infections exerted serum TAA patterns similar to healthy controls., Conclusion: The concentration of some TAAs may be elevated in the sera of patients with SSc or SLE in comparison to healthy subjects. Pathogenically, most of these TAAs contain carbohydrate motifs and thus they may be involved in inflammation-associated adhesive events. Furthermore, the production of some TAAs may correlate with organ involvement or disease activity in scleroderma or lupus.
- Published
- 2008
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99. Cutaneous vasculitis as an initiating paraneoplastic symptom in Hodgkin lymphoma.
- Author
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Simon Z, Tarr T, Tóth L, Szucs G, and Illés A
- Subjects
- Adult, Epstein-Barr Virus Infections complications, Humans, Male, Hodgkin Disease complications, Paraneoplastic Syndromes etiology, Skin Diseases, Vascular etiology, Vasculitis etiology
- Abstract
Skin vasculitis may be associated with infections and autoimmune diseases. Furthermore, vasculitis may appear as a paraneoplastic symptom. A 19-year-old male patient was examined with swollen joints and papules presented on lower extremitis. Laboratory results showed high erythrocyte sedimentation ratio, positive C reactive protein, increased number of leukocytes and high circulating immune complex level. Histopatology of skin biopsy specimen proved vasculitis. ANCA was not present. No other changes could be observed besides skin involvement. Symptoms disappeared on 0.5-mg/bwkg methylprednisolon therapy. Few weeks later, enlarged cervical lymph nodes developed besides fever and weight loss. Biopsy indicated the presence of mixed cell type Hodgkin lymphoma. Appropriate examinations revealed clinical stage III/B with favorable prognosis (IPS=2). After eight cycles of ABVD therapy complete remission was achieved as confirmed by FDG-PET. As a consequence of the treatment of Hodgkin lymphoma, vasculitis also disappeared. The present case report calls to attention the importance of careful examinations to exclude other diseases, especially malignancies that may remain at the background of cutaneous vasculitis. Treatment of the primary disease also results in the improvement of secondary skin vasculitis.
- Published
- 2008
- Full Text
- View/download PDF
100. Reduced paraoxonase1 activity is a risk for atherosclerosis in patients with systemic lupus erythematosus.
- Author
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Kiss E, Seres I, Tarr T, Kocsis Z, Szegedi G, and Paragh G
- Subjects
- Adult, Apolipoprotein A-I blood, Apolipoproteins B blood, Autoantibodies blood, Carboxylic Ester Hydrolases metabolism, Cholesterol, HDL blood, Cholesterol, LDL blood, Female, Humans, Lipoprotein(a) blood, Male, Phenotype, Risk Factors, Aryldialkylphosphatase metabolism, Atherosclerosis complications, Atherosclerosis metabolism, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic metabolism
- Abstract
Excessive lipid peroxidation is a major factor of accelerated atherosclerosis, observed in patients with systemic lupus erythematosus (SLE). We aimed at the present study to determine the paraoxonasel (PON1) and arylesterase activities, and lipid-profile in 37 SLE patients and 30 age-/sex-matched controls. Association was analyzed between PON1 activity and SLEDAI, CRP, anti-oxLDL, and antiphospholipid antibody (aPL) levels, steroid dose, and atherothrombotic events. The age of patients was 40.8 +/- 13.9 year, follow-up time 6.7 +/- 6.2 year, SLEDAI 2 (0-15). PON1 and arylesterase activities were measured spectrophotometrically using paraoxon and phenyl acetate as substrates, respectively. Phenotypic distribution of PON1 was determined by dual substrate method. We measured antioxLDL and aPL levels by ELISA, the CRP by automated immunoassay. PON1 activity (121.9 +/- 65.9 U/mL) was reduced significantly (P < 0.001) in SLE as compared to control (188.1 +/- 78.9 U/mL), but arylesterase activity was not different. A negative correlation was found between PON1 activity and age. PON1 activity did not correlate with other measured parameters. Reduced PON1 activity associated with clinical atherothrombotic complications (P < 0.01). High activity BB phenotype was not present in SLE. Lipid parameters (TC, LDL-C, HDL-C, ApoAI, and ApoB) were within normal range in both groups. Results indicated reduced PON1 activity in lupus patients despite long disease duration and low inflammatory activity, and it was evidenced as a risk for atherosclerotic complications. As the arylesterase activity was normal, further examinations are required to find other mechanisms, such as anti-PON1 antibodies, genetic polymorphisms, and difference in distribution of HDL-subfractions or enzyme abnormalities in HDL remodeling.
- Published
- 2007
- Full Text
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