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Selected AbstractsMDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: A report from the Children's Oncology Group,PEDIATRIC BLOOD & CANCER, Issue 2 2010Christine L. Phillips MD Abstract Background The variant polymorphism in the gene MDM2, SNP309, leads to increased level of mdm2 protein and subsequent downregulation of p53 tumor suppressor pathway. Presence of this single nucleotide polymorphism (SNP) has been associated with earlier tumorigenesis in patients with Li,Fraumeni syndrome, as well as decreased survival in patients with CLL. In addition, cells homozygous (G/G) for SNP 309 were found to have 10-fold increase resistance to topoisomerase II inhibitors in vitro. Procedure We genotyped children (n,=,575) with de novo acute myeloid leukemia (AML) treated on three Children's Oncology Group protocols (CCG 2941/2961/AAML 03P1) for the presence of SNP309. Healthy blood donors were genotyped as control population. Results The variant G/G genotype was associated with an increased susceptibility to AML (OR 1.5; P,=,0.049). However, the presence of the variant allele at SNP309 did not modify disease response or toxicity in children treated on CCG protocols 2941/2961. Conclusions The variant SNP 309 influences susceptibility to pediatric AML, but does not impact overall response to therapy. Pediatr Blood Cancer. 2010;55:248,253. © 2010 Wiley,Liss, Inc. [source] Concurrence of hepatitis B surface antibodies and surface antigen: implications for postvaccination control of health care workersJOURNAL OF VIRAL HEPATITIS, Issue 2 2002H. L. Zaaijer Among 1081 persons testing positive for hepatitis B surface antigen, 106 (10%) tested positive for antibodies to surface antigen (anti-HBs) in the same blood sample. Thirty of these persons were studied in detail: seven tested positive for hepatitis B e-antigen, nine were apparently healthy blood donors, and in 14 chronic infection could be demonstrated in follow-up samples. Frozen samples of 14 persons were available for additional quantitative anti-HBs testing using another anti-HBs assay: three showed no anti-HBs reactivity, seven showed borderline anti-HBs levels (1,5 IU/L), and anti-HBs titres ranged from 23 to 66 IU/L in four HBsAg-positive persons, including an apparently healthy blood donor. Thus, after hepatitis B vaccination of medical personnel, presence of anti-HBs may erroneously suggest immunity, while in fact chronic infection with hepatitis B virus is present. [source] Comparative study on antibodies to human and bacterial 60 kDa heat shock proteins in a large cohort of patients with coronary heart disease and healthy subjectsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2001Z. Prohászka Background Recent observations indicate an association between antibodies against mycobacterial heat shock protein (hsp65) and coronary heart disease (CHD). Previously, we reported on marked differences in antigen specificity and complement activating ability of anti-hsp65 antibodies and auto-antibodies against human heat shock protein, hsp60. Here, we investigated whether there are differences between antih-sp65 and anti-hsp60 antibodies in their association with CHD. Design We measured by ELISA the levels of antibodies to hsp65, hsp60 and E. coli -derived GroEL in three groups: Group I, 357 patients with severe CHD who underwent by-pass surgery; Group II, 67 patients with negative coronary angiography; Group III, 321 healthy blood donors. Antibodies against Helicobacter pylori were also measured by commercial ELISA. Results As calculated by multiple regression analysis, the levels of anti-hsp60 auto-antibodies were significantly higher in Group I compared to Group II (P = 0·007) or Group III (P < 0·0001). By contrast, although concentrations of anti-hsp65 and anti-GroEL antibodies in Group I were higher than in Group III, no significant differences between Group I and Group II were found. Antibodies to the two bacterial hsp strongly correlated to each other, but either did not correlate or weakly correlated to hsp60. In Group I, serum concentrations of anti- H.pylori antibodies significantly correlated with those of anti-hsp65 and anti-GroEL antibodies but they did not correlate with the anti-hsp60 antibodies. Conclusion As to their clinical relevance, a remarkable difference become evident between antibodies to human hsp60 and antibodies against bacterial hsp in the extent of association with CHD. On the basis of these findings and some pertinent literature data, an alternative explanation for the association between high level of anti-hsp antibodies and atherosclerotic vascular diseases is raised. [source] Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patientsEXPERIMENTAL DERMATOLOGY, Issue 5 2010Enno Schmidt Please cite this paper as: Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patients. Experimental Dermatology 2010; 19: 458,463. Abstract:, Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are intraepidermal blistering skin diseases. PV is characterised by autoantibodies directed against desmoglein (Dsg) 3 and in patients with the mucocutaneous variant also against Dsg 1, whereas in PF, only Dsg 1 is targeted. Here, ectodomains of Dsg 3 and Dsg 1 were recombinantly expressed in a human cell line (HEK293) and applied as authentic solid phases in ELISA test systems. Autoantibodies against Dsg 3 and/or Dsg 1 could be detected in 71 (100%) of 71 PV sera and against Dsg 1 in 48 (96%) of 50 PF sera. Control sera showed reactivity with Dsg 3 and Dsg 1 in 0.2% and 0.7%, respectively, of 401 healthy blood donors and in 2.1% of 48 randomly selected patients with bullous pemphigoid. No reactivity with Dsg 1 and 3 was detected in 21 patients with linear IgA disease. For both pemphigus variants, a statistically significant correlation between clinical severity and autoantibody levels was observed as demonstrated for 10 PV and 5 PF patients. In conclusion, the use of the ectodomains of Dsg 3 and 1 as target antigens expressed in a human cell line resulted in sensitive and specific ELISA systems for both diagnosis and monitoring of PV and PF. [source] Human platelet antigens polymorphisms and susceptibility of thrombosis in hemodialysis patientsHEMODIALYSIS INTERNATIONAL, Issue 3 2008Yousr GORGI Abstract To investigate the association between the polymorphisms of human platelet antigen (HPA)-1,2,3,4,5 and susceptibility to develop thrombosis accident in arteriovenous fistula (AVF), genomic DNA of 112 hemodialysis (HD) patients and 100 healthy blood donors were genotyped by PCR-SSP. The patients were classified into 2 groups: G1 included 54 HD patients presented at least one thrombotic episode on the level of the AVF, and G2 included 58 HD patients without any episode of thrombosis. The allelic frequencies of HPA-1, 2, 3, and 5 among patients and controls did not reveal significant differences. However, the HPA-4b allele was significantly more frequent in G1 than in controls or in G2 patients (23.1% vs. 11.5% and 0.9%, respectively), p<0.01 and p<0.001. The genotype distribution of HPA-4 polymorphism reveals that the HPA-4a4b genotype was more frequent in G1 patients (23/54: 42.6%) than in all HD patients (25/112: 22.3%) or in G2 patients (1/58: 1.72%) (p<0.001, odds ratio: 45.6). Among 24 HD patients with HPA-4a4b genotype, 23 (96%) developed at least 1 or more thrombotic episode on the level of their AVF. However, 30 patients (34.5%) among 87 HD patients with HPA-4a4a genotype presented thrombotic episode (p<0.001). These results reveal a significant association between HPA-4a4b and thrombosis, and it is likely that HPA polymorphisms could be useful markers for potential risk of thrombosis in hemodialysis. [source] Identification of plasma membrane autoantigens in autoimmune hepatitis type 1 using a proteomics tool,,HEPATOLOGY, Issue 3 2008Fatima Tahiri Autoimmune hepatitis (AIH) is a liver disease with circulating autoantibodies predominantly directed against widely held cellular components. Because AIH is a liver-specific disease, autoantibodies against plasma membrane antigens may be involved in its pathogenesis and have been reported; however, no definite identification has been described. We thus investigated the fine specificity of anti-hepatocyte plasma membrane autoantibodies in type 1 AIH (AIH-1) using a proteomic tool. A plasma membrane,enriched fraction was validated using enzymatic activity and western blot analysis experiments. Sera from AIH-1 patients (n = 65) and from 90 controls, that is, healthy blood donors (n = 40) and patients with systemic diseases (n = 20) or other liver diseases (n = 30), were studied by immunoblot performed with plasma membrane proteins resolved by either sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) or 2-dimensional (2D) electrophoresis. Proteins contained in the immunoreactive spots were identified by sequences provided by ion-trap mass spectrometry. Hepatocytes probed with sera were also studied using confocal immunofluorescence and immunoelectron microscopy. The more prominent bands stained by patient sera were located at 38 kDa, 48, 50, 52 kDa, 62 kDa, 70 kDa, and a 95-kDa double band. Six proteins with known potential plasma membrane expression were identified: liver arginase (38 kDa), cytokeratins (CK) 8 and 18 (48-52 kDa), heat shock proteins (HSP) of 60, 70, 90 kDa, and valosin-containing protein (VCP) of 92 kDa. The presence of anti-membrane antibodies was confirmed by immunofluorescence and immunoelectron microscopy. Conclusion: Overall, our data demonstrate that liver arginase, CK 8/18, HSP 60, HSP 70, HSP 90, and VCP represent potential candidate targets on liver membrane for autoantibodies in AIH-1. (HEPATOLOGY 2008;47:937,948.) [source] Sex-specific association of the human PTPN22 1858T-allele with type 1 diabetesINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2007C. Nielsen Summary Type 1 diabetes (T1D) is a common organ-specific autoimmune disease of complex aetiology, involving the interaction of a large number of disease-associated genes. By comparison of a Danish population sample of 253 Caucasian children and adolescents with T1D and a control group consisted of 354 unrelated healthy blood donors, the present study provides evidence of an isolated association of the disease-associated PTPN22 1858T-allele with T1D to the female sex. Furthermore, the present data suggest that PTPN22 genotypes affect the age of onset in a sex-specific manner. The increased frequency of the risk allele and its association with age at onset in female T1D children and adolescents indicates that the genetic contribution to disease pathogenesis is more prominent in females in this population of Danish patients. [source] Diagnostic value of an enzyme-linked immunosorbent assay using the recombinant CT694 species-specific protein of Chlamydia trachomatisJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2009O. Frikha-Gargouri Abstract Aim:, To study the performance of the CT694 protein in relation to the microimmunofluorescence (MIF) and the pELISA tests for the serodiagnosis of Chlamydia trachomatis infections. Methods and Results:, The CT694 protein was produced as recombinant protein and was used as antigen in ELISA test for the detection of C. trachomatis IgG antibodies. The performance of the developed ELISA test was compared to the MIF test at two cut-off values of 16 and 64, and to the specific pELISA test using a panel of 342 sera. These sera were from children MIF C. trachomatis and Chlamydophila pneumoniae negative, patients MIF C. pneumoniae positive, patients MIF C. trachomatis positive, patients suspected to have chlamydial infections diagnosed by the Cobas Amplicor test, healthy blood donors and prostitutes. Our results indicate that the developed ELISA test has performed better compared with the MIF and the pELISA tests. The highest performance was obtained when comparing the developed ELISA test in relation to the pELISA, yielding an overall sensitivity and specificity of 85% and 87% respectively. Conclusions:, The CT694 ELISA showed the best performance when compared to the species-specific pELISA test and may be used for the serodiagnosis of C. trachomatis infections. Significance and Impact of the Study:, The CT694 ELISA test responds to the criteria of both sensitivity and specificity according to the MIF and pELISA tests and may be used for serodiagnosis of C. trachomatis infections. [source] Measurement of gp210 autoantibodies in sera of patients with primary biliary cirrhosisJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 4 2007Alicja Bauer Abstract Primary biliary cirrhosis (PBC) is an autoimmune liver disease with unknown etiology. Patients with PBC have antimitochondrial autoantibodies (AMA) and additionally 50% of them have antinuclear antibodies (ANA). A 15,amino acid fragment (DRKASPPSGLWSPAY) from the C-terminal part of the nuclear envelope glycoprotein gp210 has been proposed as one of the antigenic targets for ANA. The aim of this work was to develop an immunoenzymatic assay for determination of gp210 autoantibodies using for its binding a synthetic pentadecapeptide derived from the gp210 amino acid sequence and to determine level of these autoantibodies in sera of patients with PBC and other autoimmune liver diseases from Poland. Polystyrene microtitration plates coated with the synthetic peptide were consecutively incubated with diluted sera, anti-human immunoglobulin G (IgG) antibodies conjugated with horseradish peroxidase, and with tetramethylobenzidine. Optical density (OD) was read at 450 nm. The mean values of the intra- and interassay of variation coefficients of the test were 4.1 and 10.2%, respectively. Anti-gp210 was detected in 44% of PBC patients and in 6% of patients with PSC. The results were negative for healthy blood donors and other controls. The specificity of the test was 99%, so the anti-gp-210 autoantibodies estimated on DRKASPPSGLWSPAY can be a reliable marker of PBC. J. Clin. Lab. Anal. 21:227,231, 2007. © 2007 Wiley-Liss, Inc. [source] Inhibitory effects of N -acetylcysteine on scavenger receptor class A expression in human macrophagesJOURNAL OF INTERNAL MEDICINE, Issue 5 2002L. SVENSSON Abstract.,Svensson L, Norén K, Wiklund O, Lindmark H, Ohlsson B, Mattsson Hultén L (Wallenberg Laboratory for Cardiovascular Research, The Sahlgrenska Academy at Göteborg University, Göteborg; and AstraZeneca, Mölndal, Sweden). Inhibitory effects of N -acetylcysteine on scavenger receptor class A expression in human macrophages. J Intern Med 2002; 251:. Objective.,The formation of foam cells from monocyte-derived macrophages involves the uptake of modified lipoproteins by scavenger receptors. Antioxidants inhibit lipoprotein oxidation and may also modulate gene expression. We investigated the effect of the antioxidant N -acetylcysteine on the expression of the class A scavenger receptor (SR-A) types I and II in human macrophages. Design.,Monocytes and macrophages from healthy blood donors and plaque-derived macrophages from patients undergoing carotid endartherectomy were used for experiments. SR-A mRNA was analysed with quantitative and semiquantitative reverse transcription-polymerase chain reaction, and ligand binding and uptake were assessed with 125I-labelled acetylated low-density lipoprotein (LDL). Results.,Incubation of monocytes and monocyte-derived macrophages with N -acetylcysteine decreased both SR-A I and II mRNA expression. N -Acetylcysteine also reduced SR-A mRNA in lesion-derived cells. Binding and uptake of 125I-acetylated LDL was decreased after brief incubation with N -acetylcysteine. After longer periods of incubation with N -acetylcysteine we observed an increased degradation of lipoproteins. Conclusions.,Our results imply that N -acetylcysteine leads to a decrease in SR-A mRNA and initially also to an attenuated uptake of modified lipoproteins. This adds more to the knowledge about the cellular actions of this drug. [source] Human papillomavirus DNA detected in peripheral blood samples from healthy Australian male blood donorsJOURNAL OF MEDICAL VIROLOGY, Issue 10 2009Alice Che-Ha Chen Abstract Recent studies have shown that human papillomavirus (HPV) DNA can be found in circulating blood, including peripheral blood mononuclear cells (PBMCs), sera, plasma, and arterial cord blood. In light of these findings, DNA extracted from PBMCs from healthy blood donors were examined in order to determine how common HPV DNA is in blood of healthy individuals. Blood samples were collected from 180 healthy male blood donors (18,76 years old) through the Australian Red Cross Blood Services. Genomic DNA was extracted and specimens were tested for HPV DNA by PCR using a broad range primer pair. Positive samples were HPV-type determined by cloning and sequencing. HPV DNA was found in 8.3% (15/180) of the blood donors. A wide variety of different HPV types were isolated from the PBMCs; belonging to the cutaneous beta and gamma papillomavirus genera and mucosal alpha papillomaviruses. High-risk HPV types that are linked to cancer development were detected in 1.7% (3/180) of the PBMCs. Blood was also collected from a healthy HPV-positive 44-year-old male on four different occasions in order to determine which blood cell fractions harbor HPV. PBMCs treated with trypsin were negative for HPV, while non-trypsinized PBMCs were HPV-positive. This suggests that the HPV in blood is attached to the outside of blood cells via a protein-containing moiety. HPV was also isolated in the B cells, dendritic cells, NK cells, and neutrophils. To conclude, HPV present in PBMCs could represent a reservoir of virus and a potential new route of transmission. J. Med. Virol. 81:1792,1796, 2009. © 2009 Wiley-Liss, Inc. [source] RANKL/OPG/TRAIL plasma levels and bone mass loss evaluation in antiretroviral naive HIV-1-positive menJOURNAL OF MEDICAL VIROLOGY, Issue 10 2007Davide Gibellini Abstract Osteopenia and osteoporosis are common in HIV-1-infected individuals and represent a challenge in clinical and therapeutic management. This report investigated osteopenia/osteoporosis in a group of 31 antiretroviral naive HIV-1-positive men and the role of specific molecules belonging to TNF and the TNF-receptor family in HIV-1-related bone mass loss. Osteoprotegerin (OPG), the receptor activator of NF-,b-ligand (RANKL), and the TNF-related apoptosis-inducing ligand (TRAIL) were significantly increased in the plasma of antiretroviral naive HIV-1-positive patients compared to a control group of healthy blood donors. In addition, TRAIL and RANKL plasma concentrations were positively correlated to HIV-1-RNA viral load. Measurement of bone mineral density in 20 out of 31 HIV-1-positive subjects disclosed osteopenia/osteoporosis in 40% of these patients. The antiretroviral naive HIV-1-positive subjects with low bone mineral density had a decreased plasma OPG/RANKL ratio and a plasma RANKL concentration >500 pg/ml. Together, these data indicate that plasma concentrations of specific factors involved in bone homeostasis were increased during HIV-1 infection and that RANKL and OPG/RANKL ratio deregulation may be involved in osteopenia/osteoporosis occurring in antiretroviral naive HIV-1 individuals. J. Med. Virol. 79:1446,1454, 2007. © Wiley-Liss, Inc. [source] Human CD4+ T-cell epitope repertoire on the C2 domain of coagulation factor VIIIJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2003M. T. Reding Summary., Approximately 25% of severe hemophilia A patients develop antibodies (Ab) that neutralize the procoagulant function of factor (F)VIII (inhibitors). Autoimmune FVIII inhibitors may develop in individuals without congenital FVIII deficiency and cause acquired hemophilia. Low titers of anti-FVIII Ab may be present in hemophilia A patients without inhibitors and in healthy blood donors. FVIII-specific CD4+ T-cells drive the synthesis of anti-FVIII Ab. We examined the epitope repertoire of CD4+ T-cells from 15 healthy subjects, 10 hemophilia A patients without inhibitors, 11 hemophilia A patients with inhibitors, and six acquired hemophilia patients. Blood CD4+ T-cells were challenged in proliferation assays with a panel 16 overlapping synthetic peptides, spanning the sequence of the FVIII C2 domain. The sequence region 2291,2330 contained the most frequently and strongly recognized peptides in each of the four subject groups. Crystallographic B factor data and the location of these peptides within the three-dimensional structure of the C2 domain confirm that this region has a high degree of solvent exposure and flexibility within the peptide backbone, which are structural features typical of immunodominant universal CD4+ epitopes. Furthermore, this sequence region overlaps inhibitor-binding sites, suggesting that CD4+ T-cells recognizing peptide sequences within this region might be involved in inhibitor synthesis. The sequence regions 2191,2210 (recognized strongly by each study group except hemophilia A patients with inhibitors) and 2241,2290 (recognized primarily by acquired hemophilia patients and healthy subjects) share the same structural features, and also overlap inhibitor-binding sites. Although similar, there appear to be important differences in the CD4+ epitope repertoires of congenital and acquired hemophilia patients. [source] Regulatory polymorphisms in the IL-10 gene promoter and HBV-related acute liver failure in the Chinese populationJOURNAL OF VIRAL HEPATITIS, Issue 11 2009Z. Yan Summary., Recent reports indicated that high levels of interleukin 10 (IL-10) contribute to the monocytes paralysis and poor clinical outcome in acute liver failure (ALF). Polymorphisms in the promoter region of IL-10 affect IL-10 production and confer susceptibility to inflammatory diseases. The aim of this study was to determine the possible association of the three polymorphisms (A-1082G, T-819C, A-592C) in the IL-10 gene promoter with the susceptibility to hepatitis B virus (HBV)-related ALF in a Chinese population. The IL-10 gene promoter polymorphisms were genotyped in 414 unrelated healthy blood donors, 367 asymptomatic HBV carriers and 345 HBV-related ALF patients. Functional analyses were conducted to verify the biological significances of the associated genetic variations. The allele frequencies of IL-10,592C and ,819C were significantly higher in HBV-related ALF patients than in blood donors and asymptomatic HBV carriers. Logistic regression analysis and stratification analysis with adjustment for age and sex indicated that the polymorphisms of A-592C and T-819C were associated with susceptibility to HBV-related ALF (P = 6.9 × 10,7), and the -1082A-819C-592C haplotype in the IL-10 gene promoter were associated with an increased susceptibility to ALF in HBV carriers (dominant model, P = 0.0002, odds ratio = 1.60, 95% CI 1.25,2.07). Functional analyses showed that the A-592C polymorphism is a nuclear proteins binding site, and the disease susceptible ,592C allele had a higher transcription activity compared with ,592A allele. This study emphasizes the importance of IL-10 in the pathophysiology of HBV-related ALF on the population level. [source] Concurrence of hepatitis B surface antibodies and surface antigen: implications for postvaccination control of health care workersJOURNAL OF VIRAL HEPATITIS, Issue 2 2002H. L. Zaaijer Among 1081 persons testing positive for hepatitis B surface antigen, 106 (10%) tested positive for antibodies to surface antigen (anti-HBs) in the same blood sample. Thirty of these persons were studied in detail: seven tested positive for hepatitis B e-antigen, nine were apparently healthy blood donors, and in 14 chronic infection could be demonstrated in follow-up samples. Frozen samples of 14 persons were available for additional quantitative anti-HBs testing using another anti-HBs assay: three showed no anti-HBs reactivity, seven showed borderline anti-HBs levels (1,5 IU/L), and anti-HBs titres ranged from 23 to 66 IU/L in four HBsAg-positive persons, including an apparently healthy blood donor. Thus, after hepatitis B vaccination of medical personnel, presence of anti-HBs may erroneously suggest immunity, while in fact chronic infection with hepatitis B virus is present. [source] CD46 expression and HHV-6 infection in patients with multiple sclerosisACTA NEUROLOGICA SCANDINAVICA, Issue 4 2009R. Alvarez-Lafuente Objectives,,, The aim of this study was to investigate the possible association between the levels of the CD46 expression, and the presence and viral load of HHV-6 in patients with multiple sclerosis (MS). Methods,,, We collected blood and serum samples of 103 patients with MS and the same number of healthy blood donors (HBD); total DNA and RNA was extracted from peripheral blood mononuclear cells (PBMCs) and serum, and then analyzed using quantitative real-time PCR for the detection of CD46 transcripts and HHV-6 genomes; the expression of rRNA18s was used for the calculation of the relative expression of CD46. Results,,, Almost 80% of patients with MS had increased levels of CD46 in comparison with HBD, and a positive correlation was also found between the over-expression of CD46 in patients with MS and the HHV-6 DNA prevalence and viral load in the blood and serum. Discussion,,, Therefore, the up-regulation of CD46 expression in patients with MS with HHV-6 infection could constitute an immunopathogenic factor that should be further investigated to elucidate its role in MS. [source] Anti-endothelial cell antibodies in rheumatic heart diseaseCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2010V. Scalzi Summary To evaluate the anti-endothelial cell antibodies (AECA), anti-cardiolipin antibodies (aCL) and serum mannose-binding lectin (MBL) profiles of a large cohort of Yemeni patients with rheumatic heart disease (RHD) and to correlate these findings with clinical features of the disease. Patients (n = 140) were recruited from Al-Thawra Hospital in Sana'a, Yemen. All had RHD diagnosed according to modified Jones' criteria. We also studied 140 sex- and age-matched healthy blood donors from the same area. Echocardiography was performed according to the recommendations of the American Society of Echocardiography. Solid phase enzyme-linked immunosorbent assays (ELISAs) were used to measure AECA and aCL titres and serum MBL levels. Forty per cent of the patients were AECA-positive, but only 7·8% were positive for aCL antibodies. Serum MBL levels were significantly lower in the RHD group (median 4221 ng/ml versus 5166 ng/ml in healthy controls). AECA titres were correlated positively with patient age, duration of RHD and the severity of aortic stenosis, as determined by echocardiographic findings. In several autoimmune rheumatic diseases, such as systemic lupus erythematosus, vasculitis and scleroderma, AECA have been shown to play pathogenic roles by producing proinflammatory and procoagulant effects (increased expression of adhesion molecules and tissue factors, increased cytokine release) in endothelial cells. In RHD, these autoantibodies might represent a pathological link between activation of the valvular endothelium and valvular damage. [source] Identification of wild type and variants of oestrogen receptors in polymorphonuclear and mononuclear leucocytesCLINICAL ENDOCRINOLOGY, Issue 1 2006Denis Stygar Summary Objective, ,Leucocytes play an important role in the pathogenesis of autoimmune and cardiovascular diseases. Clinical and epidemiological observations indicate that the sex steroid hormones, particularly oestrogens, may regulate leucocyte functions. The assumption that oestrogens have a direct effect on leucocytes has to be supported by identification of functional oestrogen receptors (ER) in leucocytes. This study aimed at investigating the presence of ER subtypes in different types of leucocytes isolated from peripheral blood of female and male donors. Design and patients, ,A total of nine men (age range 18,43 years) and nine women (age range 19,42 years) all healthy blood donors, were recruited for the study. The donors did not receive any medication or hormonal contraceptives for the last three months. Ten millilitres of peripheral blood was collected from each donor. Polymorphonuclear leucocytes (PMN) and peripheral blood mononuclear cells (PBMC) were purified by density gradient centrifugation. Measurements, ,ER, and ER, mRNA expression was measured by real-time reverse transcriptase,polymerase chain reaction (RT-PCR), and ER proteins were analysed by Western blot in the PBMC and PMN leucocyte populations. In addition, expression profiles of ER variant isoforms were characterized by conventional PCR using the splice-targeted primer approach. Results, ,Although we detected wild-type ER, and ER, mRNAs in PBMC but not in PMN cells, the ER, and ER, proteins were found in both cell types using Western blot. We observed that both ER, and ER, proteins differ in size between PMN and PBMC, suggesting that the two leucocyte populations contain diverse variant isoforms of ER, and ER,. RT-PCR analysis of exon-deleted ER splice variants revealed that PBMC express several exon-deleted variants of ER, and ER,, along with wild-type receptor, whereas the PMN cells only express exon-deleted variant isoforms and no wild-type ER, or ER,. Conclusions, ,Our study demonstrates the presence of ER, and ER, in PBMC and PMN cells from female and male donors. The ER, and ER, genes have complex transcriptional profiles, with many receptor variant isoforms being expressed. Considering the diversity of ER isoforms in leucocyte subtypes, we conclude that the expected effect of oestrogen would be highly cell type-specific. Further studies are needed to test the functional activity of ER isoforms and their relation to disease. [source] Cross-reaction between Yersinia outer membrane proteins and anti- Borrelia antibodies in sera of patients with Lyme diseaseCLINICAL MICROBIOLOGY AND INFECTION, Issue 9 2008E. Golkocheva-Markova Abstract Diagnosis of Yersinia infections accompanied by reactive arthritis could be complicated by cross-reaction with other arthritogenic bacteria. The possible cross-reaction between Yersinia antigens and anti- Borrelia antibodies in blood sera of patients with Lyme disease was studied. The occurrence of specific IgA, IgG and IgM antibodies was analyzed in serum samples from 30 patients with Yersinia -triggered reactive arthritis, 30 patients with Lyme disease and five samples from healthy blood donors. For anti- Borrelia IgG antibodies, cross-reaction was detected with YopH, YopB, V-ag, YopD, YopN, YopP and YopE, and for IgA with YopD. For IgM, no cross-reaction was detected. Owing to cross-reactivity with Borrelia, the diagnosis of Yersinia -triggered reactive arthritis should be based on a combination of serological and clinical findings. [source] | ||||||||||||||||||||||