Publications (19)61.88 Total impact
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Article: Alfacalcidol treatment restores derailed immune-regulation in patients with undifferentiated connective tissue disease.
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ABSTRACT: Vitamin D deficiency may contribute to pathological changes in the number and function of CD4+ T helper cell subsets (CD4+Th1, CD4+Th17, CD4+CD25(bright)Foxp3-natural regulatory T cells-nTreg) in patients with undifferentiated connective tissue disease (UCTD). The aim of the present study was to evaluate, whether alfacalcidol could restore immune-regulatory changes in patients with UCTD. We assessed the optimal dose of alfacalcidol that could normalize the elevated levels of IFN-γ expressed by the CD4+Th1 cells and the IL-17 expressed by Th17 cells. Furthermore alfacalcidol decreased the Th1 and Th17 related cytokine levels, repaired the nTreg/Th7 balance, and restored the functional activity of nTreg cells. Twenty one UCTD patients with Vitamin D deficiency (<30 ng/ml) were administered with three different daily doses of alfacalcidol. Seven patients were supplemented with 0.5 μg/day, 7 patients with 1.0 μg/day, and 7 patients with 1.5 μg/day alfacalcidol treatment during 5 weeks. Our results indicated that 1.0 μg/day alfacalcidol during 5 weeks was the optimal therapeutic regime to increase the vitamin D levels, repair the nTreg/Th17 balance and raise the capacity of nTreg cells to suppress the proliferation of autologous CD4+CD25- cells. 1.5 μg daily dose alfacalcidol was not more effective than the 1.0 μg/day treatment. In this study we described that vitamin D deficiency can contribute to the complex immune-regulatory abnormalities in patients with UCTD and vitamin D substitution therapy can improve the fine balance of pro- and anti-inflammatory processes in the disease.Autoimmunity reviews 01/2011; 10(3):155-62. · 6.37 Impact Factor -
Article: Measurement of interleukin-1 receptor antagonist in patients with systemic lupus erythematosus could predict renal manifestation of the disease.
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ABSTRACT: Interleukin-1 receptor antagonist (IL-1Ra) is a good indicator of disease activity in patients with systemic lupus erythematosus (SLE). Glucocorticosteroids are the most frequently used drugs in SLE. Our goal was to compare IL-1Ra activity in SLE patients with and without renal involvement and to determine the effect of different dosage of glucocorticosteroids used in 17 patients with active SLE without nephritis, 7 patients with inactive lupus nephritis (LN), and 8 patients with active LN, along with 10 healthy controls. IL-1Ra levels were measured in the serum of SLE patients by Human Luminex [100] analyzer. Both in patients with active SLE without nephritis and in patients with LN, serum levels of IL-1Ra (p<0.001) were significantly higher compared with those in the controls. IL-1Ra was significantly higher in patients with active LN than in patients with inactive LN (p = 0.028). The use of methylprednisolone was significantly higher in the active LN group compared with the inactive LN group (p = 0.013). SLE patients with higher IL-1Ra are at lower risk for developing nephritis. The higher doses of glucocorticosteroids needed in active LN could be due to steroid resistance and IL-1Ra polymorphism. Measurement of IL-1Ra levels in SLE patients could help to predict future renal involvement.Human immunology 09/2010; 71(9):874-7. · 2.55 Impact Factor -
Article: Oxidized LDL induces in vitro lymphocyte activation in antiphospholipid syndrome.
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ABSTRACT: Oxidized low-density lipoprotein (oxLDL) is a key feature of the atheromatosus plaque and plays a critical role in foam cell formation and perpetuation of inflammatory processes. In antiphospholipid syndrome (APS), oxLDL molecules form complexes with beta2GPI and become target antigens for autoantibodies, which are detectable in the sera of these patients. oxLDL takes part in the pathogenesis of APS and in the concomitant accelerated atherosclerosis, yet the exact associated immune mechanisms are not clear in details. The aim of this study was to assess the activation and proliferation response of peripheral blood mononuclear cells (PBMCs) derived from patients with APS in the presence of oxLDL. Thirteen patients with APS and nine healthy individuals were enrolled in the study. Separated PBMCs of these patients were cultured in the presence of immunogenic epitope of oxLDL. Lymphocyte proliferation and cytokine secretion (TNF-alpha, IL-2, IFN-gamma, IL-4, and IL-10) were assessed by ELISA. We found significant PBMC proliferation in APS compared to healthy controls (PI/proliferation index/APS: 1.76 vs. PI control: 0.56; p = 0.032). A significant IL-2 and IFN-gamma secretion were detected upon oxLDL stimulus in patients with APS compared to controls (IL-2 cytokine secretion index (CSI) APS: 278.5, IL-2 CSI controls: 65.1; p = 0.025; IFN-gamma CSI APS: 163.2, IFN-gamma CSI controls: 77.4; p = 0.025). Based on our findings, we assume that oxLDL via Th1-type cytokine production and lymphocyte proliferation may contribute to the perpetuation of immune processes in APS.Autoimmunity 02/2010; 43(4):334-9. · 2.47 Impact Factor -
Article: The immunoregulatory role of vitamins A, D and E in patients with primary Sjogren's syndrome.
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ABSTRACT: The aim of the present study was to investigate the immunomodulating role of fat-soluble vitamins in 25 patients with primary SS (pSS) and 15 healthy individuals. Plasma levels of vitamins A, D and E were determined by HPLC. Peripheral NK, NK T cells, T-cell subsets, B cells, IL-10 producing Tr1 cells, CD4(+)CD25(+) Treg cells and Th17 were determined by flow cytometry. Various Th1- and Th2-soluble cytokines were assessed by ELISA, whereas intracytoplasmic cytokines (IFN-gamma, IL-4, -10 and -17) were measured by flow cytometry. Correlation was assessed between vitamin levels and immunological and clinical parameters. Vitamin A levels did not differ between patients and controls, yet in patients with extraglandular manifestations (EGMs) a significant decrease in vitamin A levels was apparent compared with pSS patients without EGMs (P = 0.005). Vitamin E levels were increased in patients compared with controls (P = 0.004), whereas vitamin D levels were similar in pSS and control subjects. In patients, vitamin A showed a positive correlation with both NK cell (P = 0.038) and Th17 cell (P = 0.025), and a negative correlation with Schirmer's test values (P = 0.035). Positive correlation was found between vitamin E and NK cells (P = 0.043), Th1 cells (P = 0.049) and the Th1/Th2 ratio (P = 0.043). In the control group, we found correlation between vitamin E and serum IL-10 levels (P = 0.003). Our data suggest that fat-soluble vitamins may be important in immunoregulatory processes in patients with pSS.Rheumatology (Oxford, England) 11/2009; 49(2):211-7. · 4.24 Impact Factor -
Article: Anti-microbial antibodies in celiac disease: trick or treat?
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ABSTRACT: To determine the prevalence of a new set of anti-glycan and anti-outer membrane protein (anti-OMP) antibodies in a Hungarian cohort of adult Celiac disease (CD) patients. 190 consecutive CD patients [M/F: 71/119, age:39.9 (SD:14.1) years], 100 healthy, and 48 gastrointestinal controls were tested for glycan anti-Saccharomyces cerevisiae (gASCA), anti-laminaribioside (ALCA), anti-chitobioside, anti-mannobioside, anti-OMP antibodies and major NOD2/CARD15 mutations. Thirty out of 82 CD patients enrolled at the time of diagnosis were re-evaluated for the same antibodies after longstanding gluten-free diet (GFD). 65.9% of the CD patients were positive for at least one of the tested antibodies at the time of the diagnosis. Except anti-OMP and ALCA, anti-microbial antibodies were exclusively seen in untreated CD; however, the overall sensitivity was low. Any glycan positivity (LR+: 3.13; 95% CI: 2.08-4.73) was associated with an increased likelihood ratio for diagnosing CD. Significant correlation was found between the levels of anti-glycan and anti-endomysial or anti-transglutaminase antibodies. Anti-glycan positivity was lost after longstanding GFD. Anti-glycan antibody titers were associated with symptoms at presentation, but not the presence of NOD2/CARD15 mutations. Patients with severe malabsorption more frequently had multiple antibodies at diagnosis (P = 0.019). The presence of anti-glycan antibodies in CD seems to be secondary to the impaired small bowel mucosa which can lead to increased antigen presentation. Furthermore, anti-glycan positivity may be considered an additional marker of CD and dietary adherence.World Journal of Gastroenterology 09/2009; 15(31):3891-900. · 2.47 Impact Factor -
Article: Human leukocyte antigen-DRB1 and -DQB1 genotyping in lupus patients with and without antiphospholipid syndrome.
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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.Annals of the New York Academy of Sciences 09/2009; 1173:545-51. · 3.15 Impact Factor -
Article: Sensorineural hearing loss in patients with mixed connective tissue disease: immunological markers and cytokine levels.
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ABSTRACT: To investigate the frequency of sensorineural hearing loss (SNHL) in patients with mixed connective tissue disease (MCTD). The study population consisted of 71 patients with MCTD (69 female; 2 male), with a mean age of 57.1 +/- 7.9 years and a mean disease duration of 14.5 +/- 8.0 years. All patients underwent audiological evaluation that included pure tone and speech audiometry. In addition, the systemic manifestations of the disease and drug therapy were recorded. All patients were tested for presence of autoantibodies. Fifty-one age-matched healthy subjects served as controls. SNHL was found in 33 (46.4%) of the 71 patients with MCTD. There was no correlation between SNHL and age and disease duration. An association was found between Raynaud's phenomenon (p < 0.03), secondary antiphospholipid syndrome (APS) (p < 0.05), and SNHL. MCTD patients with SNHL had higher serum levels of anti-U1RNP (p < 0.05), antiendothelial cell antibodies (p < 0.001), and IgG type anticardiolipin antibodies (p < 0.0001) than patients without SNHL. Serum levels of interferon-gamma and tumor necrosis factor-alpha were increased in MCTD patients with SNHL compared to patients without SNHL. The absolute number of natural (CD4+CD25(high)FoxP+) regulatory T cells (Treg) was lower compared to patients without SNHL. In MCTD, SNHL is a specific organ manifestation and appears frequently. We have found that pathogenic autoantibodies, decreased levels of regulatory T cells, and overexpression of proinflammatory cytokines may play a role in the pathogenesis of immune mediated inner ear disorders in MCTD.The Journal of Rheumatology 09/2009; 36(9):1930-6. · 3.69 Impact Factor -
Article: Human Leukocyte Antigen‐DRB1 and ‐DQB1 Genotyping in Lupus Patients with and without Antiphospholipid Syndrome
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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.Annals of the New York Academy of Sciences 08/2009; 1173(1):545 - 551. · 3.15 Impact Factor -
Article: Evaluation of the combined application of ethanol-fixed and formaldehyde-fixed neutrophil substrates for identifying atypical perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease.
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ABSTRACT: No clear guidelines for indirect immunofluorescence (IIF) detection and interpretation of antineutrophil cytoplasmic antibodies (ANCA) have been proposed for inflammatory bowel diseases (IBD). We evaluated the reliability of the combined use of ethanol- and formalin-fixed neutrophil substrates to identify atypical perinuclear ANCA (P-ANCA) by IIF under routine laboratory circumstances. A total of 204 IBD patients were assessed with four different fluorescent substrates in two distinct laboratories. Antibodies against myeloperoxidase, proteinase-3, and other specific granule proteins (elastase, lactoferrin, cathepsin G, lysozyme, and bactericidal permeability-increasing protein) were measured by an enzyme-linked immunosorbent assay. The combined application of ethanol- and formalin-fixed slides to detect atypical P-ANCA resulted in a lack of agreement between assays (kappa, < or =0.39) in the interassay study and moderate agreement in the interobserver study (kappa, 0.42). After atypical and typical P-ANCA patterns were combined, the consensus improved greatly. A total of 26.9% of patients were P-ANCA positive by at least two tests (44.3% of ulcerative colitis [UC] and 13.1% of Crohn's disease [CD] patients; P < 0.0001), while overall ANCA positivity was 22.5% to 34.8%. The combined application of ethanol-fixed and formaldehyde-fixed neutrophil substrates did not facilitate differentiation between P-ANCA and atypical P-ANCA, and the results were not consistent when substrates from different sources were used. Combining all P-ANCA ensures the highest sensitivity and specificity in differentiating UC from CD.Clinical and vaccine immunology: CVI 02/2009; 16(4):464-70. · 2.37 Impact Factor -
Article: Pancreatic autoantibodies are associated with reactivity to microbial antibodies, penetrating disease behavior, perianal disease, and extraintestinal manifestations, but not with NOD2/CARD15 or TLR4 genotype in a Hungarian IBD cohort.
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ABSTRACT: Pancreatic autoantibodies (PAB) and goblet cell autoantibodies (GAB) are specific for Crohn's disease (CD) and ulcerative colitis (UC), but the sensitivity alone is low. Conventional antibodies and carbohydrates (glycans) are associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Our aim was to determine the accuracy of PAB and GAB autoantibodies as well as to study relevant phenotype-serotype associations. A Hungarian study cohort of 1092 subjects, including 689 well-characterized, unrelated IBD patients (CD: 579, m/f ratio: 274/305, duration: 7.9 +/- 11.2 years; UC: 110, m/f ratio: 53/57, duration: 8.9 +/- 9.8 years), 139 celiac patients, 100 healthy, and 64 non-IBD gastrointestinal controls were investigated. Sera were assayed for PAB-GAB IgA/IgG, anti-Omp, anti-Saccharomyces cerevisiae antibodies (ASCA), and anti-glycans. TLR4 and NOD2/CARD15 was tested by polymerase chain reaction / restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined. The prevalence of PAB was significantly more frequent in CD (41.1%) versus UC (22.7%), celiac (22.3%), and controls (8% and 4.6%, P < 0.01 for each), while GAB detection was poor in all groups except UC (15.4%). In CD the combination of PAB and/or anti-glycans/ASCA increased the sensitivity to 72% and 59%, respectively, for isolated colonic disease. PAB was associated to gylcans (odds ratio [OR] 1.74,P = 0.002), ASCA IgG/IgA (OR 1.75, P = 0.002), Omp (OR 1.86, P = 0.001) as well as perforating, perianal disease, arthritis, ocular, and cutaneous manifestations (P = 0.002-0.032). In contrast, PAB and GAB antibodies were not associated with NOD2/CARD15 or TLR4, response to medical therapy, or need for surgery. No associations were found in UC. PAB autoantibodies in combination with ASCA or anti-glycan antibodies increase the sensitivity for detecting CD, especially isolated colonic CD. Antibody response to PAB was associated with complicated disease phenotype and extraintestinal manifestations in this Eastern European IBD cohort.Inflammatory Bowel Diseases 10/2008; 15(3):365-74. · 4.86 Impact Factor -
Article: Progressive divergent shifts in natural and induced T-regulatory cells signify the transition from undifferentiated to definitive connective tissue disease.
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ABSTRACT: The objectives of the study is to determine clinical signs and distribution of peripheral T-cell subsets, B cells and T regulatory cells in patients with undifferentiated connective tissue disease (UCTD) and during the development toward well-established connective tissue diseases (CTD). The methods include 46 patients with UCTD were followed and investigated for differentiation into defined CTDs for 2 years. Cell subsets were determined on the basis of cell surface markers, intracellular cytokine production by flow cytometry and serum cytokine levels by ELISA. The results are as follows: 45.6% of UCTD patients developed into a defined CTD. The number and percentage of activated T cells, memory T cells and NKT cells were increased in patients compared with controls. In addition, in patients with UCTD, the percentage of CD4+/IFN gamma+ T(h)1 was significantly higher compared with controls and further increased in patients that developed CTDs. The percentage and absolute number of CD4+CD25+Foxp3+ regulatory T cells (Tregs) were diminished in UCTD patients compared with healthy controls, while the number of CD4+/IL-10+ Tregs increased. The conclusions are Overproduction of IFN gamma and the decrease of natural (Foxp3+) Tregs seem to be characteristic features of UCTD patients. The increased IL-10 production of CD4+ T cells might be a compensatory suppressive mechanism; however, it is probably not able to balance the overproduction of IFN gamma and the observed decrease of Foxp3+ Tregs. The shift toward T(h)1 with increased IFN gamma production in patients with UCTD combined with the degree of immunoregulatory disturbances characterized by the progressive divergent shifts in natural and induced T-regulatory cell populations signify the transition from undifferentiated to definitive CTD.International Immunology 07/2008; 20(8):971-9. · 3.41 Impact Factor -
Article: New serological markers for inflammatory bowel disease are associated with earlier age at onset, complicated disease behavior, risk for surgery, and NOD2/CARD15 genotype in a Hungarian IBD cohort.
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ABSTRACT: Antibodies to Saccharomyces cerevisiae (S. cerevisiae) (ASCA) and porin protein-C of Escherichia coli (anti-OmpC) are associated with disease phenotype and may be of diagnostic importance in inflammatory bowel diseases (IBD). Our aim was to determine whether a panel of new antibodies against bacterial proteins and carbohydrates could help differentiate among the various forms of IBD, and whether they were associated with particular clinical manifestations in a Hungarian cohort of IBD patients. Six hundred fifty-two well-characterized, unrelated, consecutive IBD patients (CD [Crohn's disease] 557, men/women 262/295, duration 8.1 +/- 11.3 yr; ulcerative colitis [UC] 95, men/women 44/51, duration 8.9 +/- 9.8 yr) and 100 healthy and 48 non-IBD gastrointestinal (GI) controls were investigated. Sera were assayed for anti-OmpC and antibodies against a mannan epitope of S. cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by reviewing the patients' medical charts. Sixty-six percent of the CD patients had at least one of the investigated antibodies. Among glycan antibodies, gASCA or the combination of gASCA and atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) was most accurate for differentiating between CD and UC. ASCA and gASCA assays performed similarly. Increasing amount and level of antibody responses toward gASCA, ALCA, ACCA, AMCA, and OmpC were associated with more complicated disease behavior (P < 0.0001) and need for surgery in CD (P= 0.023). A serological dosage effect was also observed. gASCA and AMCA antibodies were associated with NOD2/CARD15, in addition to a gene-dosage effect. No serotype-phenotype associations were found in UC. Antibody response to this new panel of serological markers was associated with complicated disease phenotype, NOD2/CARD15 genotype, and a need for surgery in this eastern European IBD cohort.The American Journal of Gastroenterology 04/2008; 103(3):665-81. · 7.28 Impact Factor -
Article: Association between human paraoxonase 1 activity and intima-media thickness in subjects under 55 years of age with carotid artery disease.
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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. · 2.72 Impact Factor -
Article: Clinical evaluation of anti-mutated citrullinated vimentin by ELISA in rheumatoid arthritis.
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ABSTRACT: Anti-cyclic citrullinated peptide (CCP) antibodies have emerged as sensitive and specific serological markers of rheumatoid arthritis (RA). However, antibodies to several other citrulline-containing proteins, including citrullinated fibrin and vimentin, have been detected in patients with RA, suggesting that citrulline is an essential constituent of autoantigens for RA-specific autoantibodies. We examined the diagnostic performance of the newly developed anti-mutated citrullinated vimentin (MCV) antibody assay. Concentrations of anti-MCV, anti-CCP2, and rheumatoid factors (RF) were determined in the sera of 237 individuals: 119 patients with RA and 118 controls, including patients with other rheumatic diseases and healthy subjects. Diagnostic properties were compared by receiver-operating characteristic curve analysis. Using manufacturer's recommended cutoff values, sensitivity and specificity of anti-MCV antibodies were 75.6% and 91.5% in RA, compared to 66.4% and 98.3% for anti-CCP2. Introducing cutoff values to obtain the same 95% specificity resulted in decreased sensitivity of the anti-MCV test (69.7%) and increased sensitivity of the anti-CCP2 test (74.8%). At optimal cutoff levels, 29.4% of IgM RF-negative cases as well as 13.3% of anti-CCP2-negative cases in the RA group were anti-MCV-positive. Double-positivity for anti-MCV and anti-CCP2 provided 98.3% specificity with 97.5% positive predictive value in RA. Overall, the performance of the novel anti-MCV ELISA for the diagnosis of RA is similar to that of the anti-CCP2 test [area under the curve 0.853 (95% CI 0.801-0.905) vs 0.910 (95% CI 0.873-0.946); p not significant]. As the diagnostic spectrum of the anti-MCV assay is somewhat different from that of anti-CCP2, the combined application of the 2 assays can improve the laboratory diagnostics of RA.The Journal of Rheumatology 09/2007; 34(8):1658-63. · 3.69 Impact Factor -
Article: Spleen autotransplantation. Morphological and functional follow-up after spleen autotransplantation in mice: a research summary.
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ABSTRACT: In 1986, we started the research on spleen surgery aimed at saving the splenic mass after its traumatic injury, with elaboration of special resection and autotransplantation techniques. The researches started on mongrel dogs and were continued on inbred mice and beagle dogs with complex histological, imaging, and laboratory investigations, following-up the function and the regeneration of autotransplanted spleen chips. Performing research on mice provided more immunological methods, such as lymphocyte subsets, immunoglobulin levels, and monitoring the phagocytic functions. Researches showed evidence also on the presence of apoptosis, furthermore, stem cell studies on regeneration and functional restoration of the spleen chips are in progress. Our results contributed to two multidisciplinary guidelines in Hungary: (1) One of them is under preparation and underlines the importance of spleen saving methods after traumatic splenic injury; (2) The second guideline shows that hemorheological changes can be early indicators of the increased sensitivity to postsplenectomy infections.Microsurgery 02/2007; 27(4):312-6. · 1.61 Impact Factor -
Article: Hemorheological follow-up after splenectomy and spleen autotransplantation in mice.
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ABSTRACT: We previously reported on a spleen autotransplantation model in mice, with spleen function studies at 6 weeks. The present study was undertaken to investigate long-term hemorheological functions. A/J and BALB/c inbred mice were divided into four groups: control, sham surgery (SH), splenectomy (SE), and spleen autotransplantation (AU). Hematological and hemorheological parameters were determined. Leukocyte counts in the SE and AU groups were significantly higher than in controls, while hematocrit levels were markedly lower. Mean erythrocyte volume did not change significantly. Platelet counts in the AU group were significantly lower, and red blood cell deformability was significantly worse in the SE group. The AU group also had increased cell transit time, but it was less than that in the SE group. The SE group showed the highest fibrinogen levels. We conclude that there are some consistent differences in hematological parameters between splenectomy and spleen autotransplantation. These data suggest that spleen autotransplantation may partially restore hemorheological functions following splenectomy.Microsurgery 02/2006; 26(1):38-42. · 1.61 Impact Factor -
Article: Distribution of peripheral blood cells in mice after splenectomy or autotransplantation.
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ABSTRACT: Our aim was to compare the distribution changes of peripheral leukocytes and erythrocytes in splenectomized and spleen-autotransplanted BALB/c female mice (n = 96), 2 and 8 months after surgery. In total, there were eight groups of animals: splenectomy, autotransplantation, sham, and untreated controls at both time points. We used the spleen-apron method of Furka et al. (Khirurgiia (Mosk) 1989;9:125-127), inserting five spleen chips into the greater omentum, for autotransplantation. Quantitative and qualitative blood cell counts and the phagocytic activity of cells (stimulated with zymosan) were determined. In splenectomized animals, the number of neutrophils significantly increased 8 months after surgery. The greatest phagocytic activity of neutrophils, however, was observed in autotransplanted animals of the same age. In splenectomized animals, erythrocyte volumes were significantly higher in the second postoperative month, but normalized by the eighth month. In conclusion, spleen autotransplantation has some beneficial effects, including clearing erythrocytes and preserving the phagocytic activity of neutrophils in peripheral blood.Microsurgery 02/2006; 26(1):43-9. · 1.61 Impact Factor -
Article: Adenosine inhibits the release of interleukin-1beta in activated human peripheral mononuclear cells.
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ABSTRACT: The effects of adenosine and subtype-specific activators of adenosine receptors (A1, A2A, A2B and A3) were studied on the release of interleukin-1beta (IL-1beta) from peripheral mononuclear cells, monocytes and lymphocytes. In the cells activated by the protein kinase C specific phorbol ester (phorbol 12-myristate 13-acetate) and Ca(2+) ionophore (A23187) both adenosine and the subtype-specific receptor agonists, CPA (A1), CGS 21680 (A2A) and IB-MECA (A3) induced a concentration-dependent inhibition of IL-1beta release. The rank order of potency in the inhibition of IL-1beta release was CPA=CGS 21680>IB-MECA>adenosine>NECA (in the presence of A1, A2A and A3 receptor inhibitors). The inhibitory actions of CPA, CGS 21680 or IB-MECA were significantly reduced in the presence of DPCPX, ZM 243185 or MRS 1191 as subtype-specific antagonists on A1, A2A and A3 adenosine receptors, respectively. It can be concluded that adenosine inhibits the release of IL-1beta from the activated human peripheral mononuclear cells. In this process A1, A2A and A3 receptors are involved.Cytokine 08/2005; 31(4):258-63. · 3.02 Impact Factor -
Article: Hematological, hemorheological, immunological, and morphological studies of spleen autotransplantation in mice: preliminary results.
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ABSTRACT: Using a spleen autotransplantation model, we conducted hematological, hemorheological, immunological, and morphological studies in mice 6 weeks after splenectomy. Sixty male and female A/J inbred mice were equally divided into 3 groups: 1) SE group, splenectomy was performed; 2) AU group, spleen chips were autotransplanted into the omentum without vascular anastomosis following splenectomy; and 3) C group (controls), no intervention in these mice. At postoperative week 6, the following studies were performed: 1) measurement of hematological parameters; 2) hemorheological studies, including relative cell transit time (RCTT) and fibrinogen levels; and 3) activity of peripheral phagocytes, measured by zymozan-induced chemiluminescence, which was calculated in stimulation index values (SI). In addition, histological investigations of autotransplants were conducted. Erythrocyte mean cell volume and platelet counts, RCTT, fibrinogen levels, and activity of phagocytes were significantly higher in the SE group, compared to those in the C group. In the AU group, these parameters were similar to those in the C group. Morphologically, the transplanted spleen showed normal histology. These data indicate that the transplanted spleens restored their function. We conclude that spleen autotransplantation reserves the normal morphology of spleen and restores most of the spleen's hematological, hemorheological, and immunological functions. Both SI index and erythrocyte deformability can be an informative detection of decreasing splenic function. These data suggest that spleen autotransplantation may provide a useful tool to prevent complications following splenectomy in a clinical setting.Microsurgery 02/2003; 23(5):483-8. · 1.61 Impact Factor
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2005–2011
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University of Debrecen
- • Medical and Health Science Centre
- • Third Department of Internal Medicine
Debrecen, Hajdu-Bihar, Hungary
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