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Antibody Levels (antibody + level)
Kinds of Antibody Levels Selected AbstractsBaseline Donor-Specific Antibody Levels and Outcomes in Positive Crossmatch Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010J. M. Gloor Renal transplant candidates with donor-specific alloantibody (DSA) have increased risk of antibody-mediated allograft injury. The goal of this study was to correlate the risk of antibody-mediated rejection (AMR), transplant glomerulopathy (TG) and graft survival with the baseline DSA level (prior to initiation of pretransplant conditioning). These analyses include 119 positive crossmatch (+XM) compared to 70 negative crossmatch (,XM) transplants performed between April 2000 and July 2007. Using a combination of cell-based crossmatch tests, DSA level was stratified into very high +XM, high +XM, low +XM and ,XM groups. In +XM transplants, increasing DSA level was associated with increased risk for AMR (HR = 1.76 [1.51, 2.07], p = 0.0001) but not TG (p = 0.18). We found an increased risk for both early and late allograft loss associated with very high DSA (HR = 7.71 [2.95, 20.1], p = 0.0001). Although lower DSA recipients commonly developed AMR and TG, allograft survival was similar to that of ,XM patients (p = 0.31). We conclude that the baseline DSA level correlates with risk of early and late alloantibody-mediated allograft injury. With current protocols, very high baseline DSA patients have high rates of AMR and poor long-term allograft survival highlighting the need for improved therapy for these candidates. [source] Reducing De Novo Donor-Specific Antibody Levels during Acute Rejection Diminishes Renal Allograft LossAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009M. J. Everly The effect of de novo DSA detected at the time of acute cellular rejection (ACR) and the response of DSA levels to rejection therapy on renal allograft survival were analyzed. Kidney transplant patients with acute rejection underwent DSA testing at rejection diagnosis with DSA levels quantified using Luminex single-antigen beads. Fifty-two patients experienced acute rejection with 16 (31%) testing positive for de novo DSA. Median follow-up was 27.0 ± 17.4 months postacute rejection. Univariate analysis of factors influencing allograft survival demonstrated significance for African American race, DGF, cytotoxic PRA >20% (current) and/or >50% (peak), de novo DSA, C4d and repeat transplantation. Multivariate analysis showed only de novo DSA (6.6-fold increased allograft loss risk, p = 0.017) to be significant. Four-year allograft survival was higher with ACR (without DSA) (100%) than mixed acute rejection (ACR with DSA/C4d) (65%) or antibody-mediated rejection (35%) (p < 0.001). Patients with >50% reduction in DSA within 14 days experienced higher allograft survival (p = 0.039). De novo DSAs detected at rejection are associated with reduced allograft survival, but prompt DSA reduction was associated with improved allograft survival. DSA should be considered a potential new end point for rejection therapy. [source] Changes of Circulating Antibody Levels Induced by ABO Antibody Adsorption for ABO-Incompatible Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009P. V. Valli ABO-incompatible kidney transplantation using immunoadsorption to remove anti-A/B antibodies has become a successful clinical practice. Since the data on the specificity of the ABO columns are controversial, the present study assessed the efficiency and specificity of the ABO immunoadsorption, the effect on total immunoglobulins and antibodies previously induced by vaccination. Anti-A/B antibodies were measured by agglutination and ABO flow cytometry, total IgG/IgM, carbohydrate- and protein-specific antibodies by nephelometry and ELISA. The first immunoadsorption not only efficiently reduced donor-specific anti-A/B IgM (81%) and IgG (56%) but also reduced compatible anti-A/B IgM (59%) and IgG (34%). The measurements of antidonor A/B antibodies by direct agglutination (IgM) or flow cytometry better represented the effective antibody levels than the indirect agglutination test (IgG). The median reduction of total IgM and total IgG levels after a single immunoadsorption was 34% and 18%, respectively. Antibodies against pneumococcus and haemophilus polysaccharide antigens were significantly reduced, whereas antitetanus and antidiphtheria protein antibodies were not affected. Intravenous immunoglobulin administration restored the protective anticarbohydrate antibody levels. In summary, immunoadsorption efficiently removed antidonor A/B antibodies, but was not specific for A/B antigens. Anti-A/B antibody levels as determined by ABO flow cytometry are useful to establish the minimal number of immunoadsorptions needed for successful ABO-incompatible transplantation. [source] Antibody levels to single bacteria or in combination evaluated against myocardial infarctionJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2008Lise Lund Håheim Abstract Background: Evidence is accumulating that oral bacteria are associated with myocardial infarctions (MI). We were interested in studying the differences in the association between single bacteria or bacteria in combination and the relation to C-reactive protein (CRP). Material and Methods: We examined the levels of antibodies against four major periodontal pathogens Porphyromonas gingivalis (PG), Aggregatibacter actinomycetemcomitans (AA), Tannerella forsythia (TF) and Treponema denticola (TD) and CRP in 548 men with a self-reported history of MI to 625 controls who took part in the Oslo II study in 2000. Results: The mean levels of bacterial antibodies were higher for the cases than the controls, but not significant as standard deviations were large. The level of CRP was higher in the cases than the controls (p=0.010). Logistic regression analyses comparing the upper quartile value with the lower value of one of either four antibodies (anti-AA, anti-TF, anti-TD and anti-PG) were significantly associated (p=0.032) with MI. Equivalent analyses of either three bacteria showed significant associations for anti-AA, anti-TD and anti-PG (p=0.036) and anti-AA, anti-PG and anti-TF (p=0.040). CRP showed an increased relative risk with increasing quartile value; trend, p=0.016, but not in multivariate analysis including the oral antigens. Conclusions: No single bacterium but rather combinations were related to increasing relative risk for MI independent of known cardiovascular risk factors. [source] The Effectiveness of Intradermal Pre-exposure Rabies Vaccination in an Australian Travel Medicine ClinicJOURNAL OF TRAVEL MEDICINE, Issue 6 2002Colleen Lau Background: The objective of the study was to assess the effectiveness of intradermal (ID) rabies vaccination and to determine whether any difference in response with age or gender exists. No published Australian data on the subject is available and controversy continues to surround the use of ID rabies vaccination for pre-exposure prophylaxis. Vaccinated travelers requiring postexposure treatment are sometimes considered unvaccinated. By confirming their immunity prior to travel, this problem may be avoided. Methods: The data was collected by retrospective analysis over 2 years at a specialized travel medicine clinic in Perth, Western Australia. The standard protocol is three ID injections of 0.1 mL, given on days 0, 7, and 28 with a booster after 12 months. The vaccine used was the Pasteur Merieux human diploid cell vaccine. Serology was performed 3 weeks after completion of the primary course or after a booster. Antibody levels were measured using the rapid fluorescent focus inhibition test, and levels of > 0.5 IU/mL were considered protective. Results: A total of 164 travelers were included in the study, of which 144 had completed the three primary ID doses, and 20 had received an ID booster after a previous primary ID course. The mean age was 34.75 years, and gender distribution was equal. The median time between vaccination and serology was 23 days. The antibody levels ranged from 0 to 50 IU/mL with a mean of 8.42 IU/mL. Three travelers had no detectable antibodies giving a seroconversion rate of 98.2%. No statistically significant correlation between age or gender and antibody levels was present. Conclusion: We have found that ID rabies vaccination is effective in a travel clinic with nurses experienced in the technique. The lower cost of ID rabies vaccination makes it accessible to a larger number of travelers. Further studies will be required to determine the duration of protection after ID vaccination and antibody response after postexposure boosters. We will continue to recommend ID rabies vaccination if there is sufficient time for serology to be performed and for results to be available prior to departure. [source] Sustainability of humoral responses to varicella vaccine in pediatric transplant recipients following a pretransplantation immunization strategyPEDIATRIC TRANSPLANTATION, Issue 8 2009Michelle Barton Abstract:, Varicella infections pose serious challenges for organ transplant recipients. To determine the safety and immunogenicity of the OMVV and determine the maintenance of OMVV responses in transplanted subjects at varying periods of immunosuppression within the first two yr following transplantation. Eligible subjects given a two-dose OMVV pretransplantation were monitored for AE. Antibody levels were assessed at baseline, six wk post-OMVV, pretransplantation and up to 24 months post-transplantation. Seroprotection was defined as ,5 gpEU. Twenty-one seronegative children were vaccinated. Following 42 doses, no vaccine-related serious AE occurred. Mab_titer were 17.8 (5.7,910.2) and 183.5 EU (18.8,8116.4) at six and 12 wk, respectively (p < 0.0001). Fourteen (66.7%) participants were transplanted at a median of 16 months (1.5,56) following OMVV and had Mab_titer of 27.2 EU (9.0,236.2) just prior to transplantation. Of 11 who had post-transplantation serology, seroprotection was sustained at three, six and 12 months post-transplantation in 10/11, 12/12 and 8/10 subjects. In five of six subjects with two-yr follow-up, antibody levels remained seroprotective. No breakthrough varicella infections occurred. The receipt of OMVV prior to transplantation induced humoral responses which persisted in the early months following transplantation and up to two yr post-transplantation and was not associated with any serious adverse consequences. [source] Cytotoxic factor-autoantibodies: possible role in the pathogenesis of dengue haemorrhagic feverFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2001U.C. Chaturvedi Abstract During dengue virus infection a unique cytokine, cytotoxic factor (hCF), is produced that is pathogenesis-related and plays a key role in the development of dengue haemorrhagic fever (DHF). However, what regulates the adverse effects of hCF is not known. We have previously shown that anti-hCF antibodies raised in mice, neutralise the pathogenic effects of hCF. In this study we have investigated the presence and levels of hCF-autoantibodies in sera of patients with various severity of dengue illness (n=136) and normal healthy controls (n=50). The highest levels of hCF-autoantibodies (mean±S.D.=36±20 U ml,1) were seen in patients with mild illness, the dengue fever (DF), and 48 out of 50 (96%) of the sera were positive. On the other hand the hCF-autoantibody levels declined sharply with the development of DHF and the levels were lowest in patients with DHF grade IV (mean±S.D.=5±2 U ml,1; P=<0.001 as compared to DF). Only one of the 13 DHF grade IV patients had an antibody level above the ,cut-off' value (mean plus 3 S.D. of the control sera). The analysis of data with respect to different days of illness further showed that the highest levels of hCF-autoantibodies were present in DF patients at >9 days of illness. Moreover, the DF patients at all time points, i.e. 1,4, 5,8 and >9 days of illness had significantly higher levels of hCF-autoantibodies (P<0.001) than patients with DHF grade I, II, III and IV. In addition DHF grade I and grade II patients had significantly more positive specimens than DHF grade III and grade IV patients at all time points. These results suggest that elevated levels of hCF-autoantibodies protect the patients against the development of severe forms of DHF and, therefore, it may be useful as a prognostic indicator. [source] Antibodies against human papillomavirus (HPV) type 16 and 18 E2, E6 and E7 proteins in sera: Correlation with presence of papillomavirus DNAJOURNAL OF MEDICAL VIROLOGY, Issue 4 2001Ricardo Rosales Abstract Human papillomavirus (HPV) infection is associated with cervical cancer. The E2 and E1 papillomavirus proteins are expressed at the early stage of infection and regulate DNA replication. The E2 protein activates and represses transcription from different HPVs promoters. At some stage when viral DNA gets integrated into the cellular genome, the E2 gene is disrupted or inactivated. This event leads to a derepression of the E6 and E7 viral oncogenes. These viral proteins are required normally for the maintenance of the malignant phenotype. Therefore, the E2, E6, and E7 proteins are present in all patients infected by papillomavirus. In this study, the association of antibody levels against E2, E6, and E7 proteins of HPV types 16, 18, and 6 was determined in relation to the presence of HPV DNA at the initial stages of HPV infection. Serum samples from 172 women with HPV infection, determined by Papanicolau (Pap) smears and colposcopy, were tested. Elevated antibody titers against E2 protein from the HPV 6 and HPV 16 were detected in 46.42 and 66.96% of the patients, respectively. Antibodies against the E7 and E6 proteins of HPV 16 were found in 51.78 and 36.60% of the patients, respectively. Antibodies against the E6 and E7 proteins of HPV 18 were 35 and 45%, respectively. A statistical difference was found for antibody titers against the E2, E6, and E7 proteins between patients with papillomavirus DNA and controls cases who had no cytological abnormalities and no HPV DNA. Sera titers were 1/500 for patients HPV positive and 1/50 for control individuals. Antibodies titers against E6 and E7 proteins were also examined in patients at 6 and 24 months after cryosurgery. In these patients, a slight decrease in the antibody level against the E2, E6, and E7 proteins was found. No correlation was found between age and number of sexual partners, with serum positivity to the E2, E6, and E7 papillomavirus proteins. These data suggest that antibodies against the E2, E6, and E7 proteins are good candidates for use as markers for monitoring cervical HPV infections. J. Med. Virol. 65:736,744, 2001. © 2001 Wiley-Liss, Inc. [source] Desmoglein 1 and 3 enzyme-linked immunosorbent assay in Iranian patients with pemphigus vulgaris: correlation with phenotype, severity, and disease activityJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2007M Daneshpazhooh Abstract Background, Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder of the skin and mucosa characterized by the presence of autoantibodies against desmoglein3 (Dsg3). Some patients also have antibodies against desmoglein1 (Dsg1). The aims of this study were to evaluate the diagnostic value of Dsg enzyme-linked immunosorbent assay (ELISA) in Iranian PV patients, to assess its correlation with the clinical phenotype and severity of disease and to investigate the changes of these antibodies after treatment. Methods, Seventy-three patients with PV (29 men, 44 women) presenting to the Pemphigus Research Unit at Razi Hospital, Tehran, Iran were enrolled. ELISAs were used to detect IgG autoantibodies reactive with the ectodomains of Dsg1 and Dsg3, and the correlation of antibodies with the clinical phenotype as well as oral and skin disease severity was assessed. In addition, the tests were repeated in 18 patients after treatment and the resulting remission. Results, Anti-Dsg1 and anti-Dsg3 were detected in 56 (76.7%) and 69 (94.5%) patients, respectively. Anti-Dsg1 and anti-Dsg3 antibodies were present in 48 (94.1%) and 50 (98%) patients with mucocutaneous type, in 2 (12.5%) and 15 (93.7%) patients with mucosal type, and in 6 (100%) and 4 (66.7%) patients with cutaneous PV, respectively. The mean anti-Dsg1 index values were significantly higher in cutaneous and mucocutaneous phenotypes than mucosal PV (P < 0.001). The mean anti-Dsg3 index values were significantly lower in cutaneous and mucosal phenotypes than mucocutaneous PV (P < 0.01). The severity of skin lesions (but not oral lesions) was correlated with anti-Dsg1 antibody level (P < 0.001); on the other hand, the severity of oral lesions (P < 0.01) as well as skin lesions (P < 0.001) was significantly correlated with anti-Dsg3 antibody levels. Both anti-Dsg1 and anti-Dsg3 levels were significantly reduced after treatment and clinical remission (P < 0.001). Conclusion,, Dsg ELISA is not only a sensitive tool for the diagnosis of PV, it can also serve as a predictive means for assessing the severity as well as for monitoring the disease activity. Although, in general, the clinical phenotype is related to the antibody profile, there are occasional cases with discordant phenotype and antibody profile. These discrepancies might be explained by genetic variations or the presence of possible minor antigens involved in the pathogenesis of pemphigus. [source] Association of antibodies to hepatitis C virus glycoproteins 1 and 2 (anti-E1E2) with HCV diseaseJOURNAL OF VIRAL HEPATITIS, Issue 5 2008M. R. B. Hamed Summary., Hepatitis C virus (HCV) causes acute and chronic liver diseases in humans. Its two envelope glycoproteins, E1 and E2, provide a target for host immune recognition. HCV genotypes are classified into six genetic groups. To study the role of anti-HCV E1 and E2 (anti-E1E2) in HCV disease, the correlation between antibody level and viral load, genotype, disease severity and response to treatment was investigated. The levels of antibodies to HCV glycoproteins E1 and E2 antibodies were evaluated in 230 sera of patients with chronic hepatitis C by enzyme-linked immunosorbent assay. The antigens used were recombinant HCV glycoproteins derived from genotype 1 (H77c) and genotype 3 (UKN3A1.28). Seroreactivity was greater when sera were tested against antigen derived from their homologous genotype than against heterologous antigen. Reactivity against UKN3A1.28 in sera from patients infected with genotype 3 was significantly higher than corresponding reactivity between patients infected with genotype 1 and H77c. The seroreactivity was inversely proportional to the viral load and to the degree of liver fibrosis. The pre-treatment level of anti-E1E2 was higher in sustained responders to combination therapy. These results demonstrate that seroreactivity against E1E2 depends upon the genotypic origin of the E1E2 antigens and the infecting genotype, and suggest a possible protective effect of anti-E1E2 against disease progression. [source] Effects of Clinacanthus siamensis leaf extract on influenza virus infectionMICROBIOLOGY AND IMMUNOLOGY, Issue 2 2009Mali Wirotesangthong ABSTRACT Ethanolic extracts of 20 medicinal plants were screened for influenza virus NA inhibition and in vitro antiviral activities using MDCK cells in an MTT assay. The vaccine proteins of influenza virus A/New Caledonia/20/99 (H1N1), mouse-adapted influenza virus A/Guizhou/54/89 (A/G)(H3N2) and mouse-adapted influenza virus B/Ibaraki/2/85 (B/I) were used in the NA inhibition assay, and mouse-adapted influenza viruses A/PR/8/34 (H1N1), A/G and B/I were used in the in vitro antiviral assay. The results of the in vitro antiviral assay indicated that the A/G virus was the most susceptible and an extract of the leaf of CS possessed the highest in vitro anti-A/G virus activity (41.98%). Therefore, the A/G virus and the CS extract were selected for studying in vivo anti-influenza virus activity. BALB/c mice were treated with CS extract (100 mg/kg per day, 5 times) orally from 4 hr before to 4 days after infection. CS extract elicited significant production of anti-influenza virus IgG1 antibody in BAW and increased mouse weight compared to oseltamivir (0.1 mg/kg per day) on day 19 or water on days 17,19 of infection. Moreover, CS extract produced a higher anti-influenza virus IgA antibody level in BAW compared to oseltamivir, and a tendency towards an increase in anti-influenza virus IgA compared to water was shown. The results suggest that CS extract has a protective effect against influenza virus infection. [source] Elevated levels of IgG3 and IgG4 subclass in paediatric cases of kala azarPARASITE IMMUNOLOGY, Issue 8 2008N. A. ANSARI SUMMARY Visceral leishmaniasis (VL) or Kala azar (KA) is a systemic disease caused by the parasites of the Leishmania donovani complex. Control measures rely on treatment with antileishmanial agents, however, fraught with problems such as toxicity or drug resistance. The incidence rate is on the rise for children, for reasons yet undefined. Previously we have shown significantly elevated level of IL-10 in children compared to adult KA cases. Here, antileishmanial antibody and C-reactive protein (CRP) levels were investigated in paediatrics and adult patients of KA and post-KA dermal leishmaniasis (PKDL). Level of IgG4 was significantly elevated in PKDL compared to KA, although total IgG and IgG1 were significantly lower. The antileishmania antibody levels of subclass IgG3 and IgG4 were found significantly elevated in paediatrics, however, levels of IgG, IgG1, IgG2 and CRP were comparable in paediatric and adult KA cases. In case of PKDL, levels of IgG and it subclass were similar in the two groups. No significant difference in antileishmanial antibody level was noticed between macular or polymorphic cases of PKDL. The differential antibody intensity in paediatric cases, together with significant level of circulating IL-10, could be considered as a marker of differential disease susceptibility. [source] Generalized Erythrodermic Pemphigus Foliaceus in a Child and Its Successful Response to Rituximab TreatmentPEDIATRIC DERMATOLOGY, Issue 2 2007Elizabeth Alvarez Connelly M.D. The nonendemic or sporadic form of this entity is rare in children and typically presents with a milder, more localized rash that usually follows a benign course of short duration. We describe an affected patient atypical in both her young age and the severity of skin findings. Our patient presented with a full body exfoliative erythroderma at 21 months of age. After an extensive work-up to determine the etiology of her exfoliative erythroderma, direct and indirect immunofluorescence studies confirmed the diagnosis of pemphigus foliaceus. Rituximab therapy was initiated based on the patient's refractory disease course to multiple immunosuppressive agents. Rituximab is a therapeutic monoclonal antibody targeting CD20, an integral membrane protein highly expressed on the surface of pre-B lymphocytes and activated mature B lymphocytes. The patient's skin exhibited marked clinical improvement after the start of rituximab infusions over 12 weeks. Her initial desmoglein 1 antibody level was greater than 1:1280, which decreased to 1:16 after seven rituximab treatments. She has had no skin flares since initiating treatment with rituximab therapy. Based on this clinical and serologic response, the use of rituximab may be helpful in the treatment of pediatric pemphigus foliaceus refractory to mainstays of therapy. [source] Lifestyle incongruity, stress and immune function in indigenous Siberians: The health impacts of rapid social and economic changeAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 1 2009Mark V. Sorensen Abstract The purpose of this study was to investigate the impact of economic and cultural change on immune function and psychosocial stress in an indigenous Siberian population. We examined Epstein-Barr virus antibodies (EBV), an indirect biomarker of cell-mediated immune function, in venous whole blood samples collected from 143 Yakut (Sakha) herders (45 men and 98 women) in six communities using a cross-sectional study design. We modeled economic change through the analysis of lifestyle incongruity (LI), calculated as the disparity between socioeconomic status and material lifestyle, computed with two orthogonal scales: market and subsistence lifestyle. EBV antibody level was significantly negatively associated with both a market and a subsistence lifestyle, indicating higher cell-mediated immune function associated with higher material lifestyle scores. In contrast, LI was significantly positively associated with EBV antibodies indicating lower immune function, and suggesting higher psychosocial stress, among individuals with economic status in excess of material lifestyle. Individuals with lower incongruity scores (i.e., economic status at parity with material resources, or with material resources in excess of economic status) had significantly lower EBV antibodies. The findings suggest significant health impacts of changes in material well-being and shifting status and prestige markers on health during the transition to a market economy in Siberia. The findings also suggest that relative, as opposed to absolute, level of economic status or material wealth is more strongly related to stress in the Siberian context. Am J Phys Anthropol, 2009. © 2008 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Estradiol Limits Viral Replication Following Intravaginal Immunization Leading to Diminished Mucosal IgG Response and Non-sterile Protection Against Genital Herpes ChallengeAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Amy Gillgrass Citation Gillgrass A, Chege D, Bhavanam S, Kaushic C. Estradiol limits viral replication following intravaginal immunization leading to diminished mucosal IgG response and non-sterile protection against genital herpes challenge. Am J Reprod Immunol 2010; 63: 299,309 Problem, Previously we reported that ovariectomized (OVX) mice receiving estradiol (E) prior to immunization with an attenuated strain of HSV-2 (TK-HSV-2) were not protected. Lack of protection in the E group was because of the inability of TK-HSV-2 to penetrate the thick keratinized epithelium. In this study, we determined the outcome of immunization after the thickening of vaginal epithelium following E-treatment waned. OVX, C57BL/6 mice were given Progesterone (P), E or saline (S) for 3 days and immunized with IVAG TK-HSV-2. Method of study, To determine the time point at which E-treated mice could be successfully immunized, the mice were inoculated with TK-HSV-2 between days 1 and 7 (ED1,ED7) post-E-treatment and challenged with IVAG HSV-2 three weeks later. Results, The level of infection post-immunization correlated with HSV-2-specific IgG antibody level, which correlated with sterile protection. No viral infection was observed in ED1,ED3 groups and no specific antibodies were detected, resulting in no protection. Moderate infection was seen in ED5 group, resulting in low antibody production and non-sterile protection in 87.5% of mice. High antibody titers and sterile protection were observed in all groups that experienced robust infection post-immunization. Conclusion, The results show that estradiol leads to limited viral replication and diminished mucosal IgG response, resulting in non-sterile immune protection against genital herpes infection. [source] Fate of the Mate: The Influence of Delayed Graft Function in Renal Transplantation on the Mate RecipientAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009J. F. Johnson Delayed graft function (DGF) in a deceased-donor renal recipient is associated with allograft dysfunction 1-year posttransplant. There is limited research about the influence to allograft function on the mate of a DGF recipient over time. Using a retrospective cohort design, we studied 55 recipients from a single center. The primary outcome was the change in glomerular filtration rate (GFR) 1-year posttransplant. The secondary outcome was the GFR at baseline. We found that mates to DGF recipients had a mean change in GFR 1-year posttransplant of ,11.2 mL/min, while the control group had a mean change of ,0.4 mL/min. The difference in the primary outcome was significant (p = 0.025) in a multivariate analysis, adjusting for cold ischemic time, panel reactive antibody level, allograft loss, human leukocyte antibody (HLA)-B mismatches and HLA-DR mismatches. No significant difference between groups was found in baseline GFR. In conclusion, mates to DGF recipients had a significantly larger decline in allograft function 1-year posttransplant compared to controls with similar renal function at baseline. We believe strategies that may preserve allograft function in these,at-risk'recipients should be developed and tested. [source] Left ventricular structure and function in patients with rheumatoid arthritis, as assessed by cardiac magnetic resonance imagingARTHRITIS & RHEUMATISM, Issue 4 2010Jon T. Giles Objective Heart failure is a major contributor to cardiovascular morbidity and mortality in patients with rheumatoid arthritis (RA), but little is known about myocardial structure and function in this population. This study was undertaken to assess the factors associated with progression to heart failure in patients with RA. Methods With the use of cardiac magnetic resonance imaging, measures of myocardial structure and function were assessed in men and women with RA enrolled in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis study, a cohort study of subclinical cardiovascular disease in patients with RA, in comparison with non-RA control subjects from a cohort enrolled in the Baltimore Multi-Ethnic Study of Atherosclerosis. Results Measures of myocardial structure and function were compared between 75 patients with RA and 225 frequency-matched controls. After adjustment for confounders, the mean left ventricular mass was found to be 26 gm lower in patients with RA compared with controls (P < 0.001), an 18% difference. In addition, the mean left ventricular ejection fraction, cardiac output, and stroke volume were modestly lower in the RA group compared with controls. The mean left ventricular end systolic and end diastolic volumes did not differ between the groups. In patients with RA, higher levels of anti,cyclic citrullinated peptide (anti-CCP) antibodies and current use of biologic agents, but not other measures of disease activity or severity, were associated with significantly lower adjusted mean values for the left ventricular mass, end diastolic volume, and stroke volume, but not with ejection fraction. The combined associations of anti-CCP antibody level and biologic agent use with myocardial measures were additive, without evidence of interaction. Conclusion These findings suggest that the progression to heart failure in RA may occur through reduced myocardial mass rather than hypertrophy. Both modifiable and nonmodifiable factors may contribute to lower levels of left ventricular mass and volume. [source] Development of Cellulose-DNA ImmunoadsorbentARTIFICIAL ORGANS, Issue 2 2002Deling Kong Abstract: The aim of this study was to prepare a DNA immunoadsorbent for the specific, extracorporeal removal of anti-DNA antibodies from the blood of patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Two kinds of cellulose beads were applied as a carrier. Calf thymus DNA was covalently coupled to the carrier using the epichlorohydrin method. Efforts were focused on optimization of conditions for activation and coupling, trying to couple as much DNA as possible to a certain amount of carrier. It was found that the activation level increased with the increase of NaOH concentration and the amount of epichlorohydrin used. The mole of epichlorohydrin must be in excess of that of NaOH because excess NaOH could react further with the epoxy groups in the beads resulting in a decrease of activation level. High activation level could be obtained in a medium of 3.0 M NaOH. The DNA coupling was found to be mainly temperature and pH dependent. Using 0.1 M Tris-HCl buffer, pH 8 at a temperature of 50,90°C, more than 3 mg of DNA could be coupled to 1 ml of wet beads. Prolonging the coupling reaction under 50°C to 72 h resulted in the same coupling capacity as that obtained under 90°C. To evaluate the adsorption ability for anti-DNA of this immunoadsorbent, batch and circulation tests were applied using SLE patient plasma. The immunoadsorbents showed excellent adsorption capacity, especially the cellulose with smaller size (200,300 ,m). The incubation of 20 ml of patient's plasma with 1 ml of adsorbent resulted in an 80% decline in the anti-DNA antibody level. In the circulation tests, 30 ml of plasma was circulated through a column containing 3 ml of adsorbent. The maximum decline in anti-DNA level, 80%, was obtained after 60 min. Such high adsorption capacity and high adsorption rate suggest this immunoadsorbent may be used for treatment. For comparison, 1,4-butanediol diglycidyl ether activation method and other DNA sources were tested with the same protocol. [source] Development of a DNA Immunoadsorbent: Coupling DNA on Sepharose 4FF by an Efficient Activation MethodARTIFICIAL ORGANS, Issue 11 2000De-Ling Kong Abstract: To remove anti-DNA antibodies from a patient's plasma with systemic lupus erythematosus (SLE), a DNA immunoadsorbent was developed by covalently coupling calf thymus DNA on activated Sepharose 4FF. Sepharose 4FF was activated with 5-norbornene-2,3-dicarboximido carbonochloridate (Cl-CO-ONB), which was proven to be a very effective method for preparation of affinity chromatographic adsorbents. The activation was carried out in dry acetone using 4-(dimethylamine)pyridine (DMAP) and triethylamine (TEA) as catalysts at 4°C or at room temperature. The coupling of DNA to the activated support was investigated as a function of pH, temperature, time, concentration of DNA, and activation level. It was found that the pH for optimal coupling is 3.0, and the amount of coupled DNA increases with an increase either in the concentration of DNA or the activation level. The maximum amount of coupled DNA could reach 1.0 mg DNA/ml support. The incubation of 5 to 20 ml of SLE plasma with 1.0 ml of adsorbent resulted in an 80 to 90% decline in the anti-DNA antibody level. Nonspecific adsorption for normal IgG and total protein is less than 15%. [source] Chemical induction of HO-1 suppresses lupus nephritis by reducing local iNOS expression and synthesis of anti-dsDNA antibodyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2004Y. TAKEDA SUMMARY There is accumulating evidence that haem oxygenase (HO)-1 plays a protective role in various disorders. The beneficial efficacy of HO-1 induction therapy has been shown in renal diseases such as glomerulonephritis, interstitial nephritis and drug induced nephrotoxicity. However, involvement of HO-1 in the development of autoimmune renal diseases remains uncertain. To assess the clinical efficacy of HO-1 induction therapy for lupus glomerulonephritis, MRL/lpr mice were intraperitoneally injected with 100 µmol/kg hemin, a potent HO-1 inducer, or PBS as controls, once a week from 6 weeks of age to 21,24 weeks-old. We found that treatment with hemin led to a significant reduction of proteinuria and remarkable amelioration of glomerular lesions accompanied by decreased immune depositions. In addition, the circulating IgG anti-double-stranded DNA antibody level was significantly decreased in hemin treated mice when compared with controls. A single intraperitoneal injection with hemin resulted in reduction of inducible nitric oxide synthase expression in the kidney and spleen, and serum interferon- , level. Our results suggest that HO-1 induction therapy ameliorates lupus nephritis by suppressing nitric oxide (NO) dependent inflammatory responses and attenuating production of pathogenic autoantibodies. [source] Coeliac disease and Type 1 diabetes mellitus , the case for screeningDIABETIC MEDICINE, Issue 3 2001G. K. T. Holmes SUMMARY Aim To review the relationship between coeliac disease and Type 1 diabetes mellitus with emphasis on prevalence of coeliac disease, presentation and implications for screening. Methods Papers collected over many years by the author have been included in the review and a literature search employing Medline was undertaken to August 2000. Search words used were coeliac disease and diabetes mellitus. Results Twenty papers exploring the prevalence of coeliac disease by serological screening of Type 1 diabetes in children, eight in adults and two including both groups were found. An additional 48 papers are included and relate to serological screening tests for coeliac disease, expressions and complications of coeliac disease, the value of GFD and the genetics of the two conditions. Unless formal screening studies are undertaken coeliac disease will not be diagnosed because patients are asymptomatic, have atypical symptoms or even in those with symptoms the diagnosis is overlooked. Based on small bowel biopsy, diagnosis the prevalence of coeliac disease in Type 1 diabetes in children is 1:6 to 1:103 and in adults 1:16 to 1:76. Patients may improve following the start of a gluten-free diet (GFD) in terms of symptoms, growth in children, serum antibody levels, haematological and biochemical indices, morphology of the small intestinal mucosa and control of diabetes. Conclusion Coeliac disease commonly occurs in Type 1 diabetes. It is recommended that screening for coeliac disease should be part of the routine investigation and offered to all patients because of the high prevalence and the potential benefits of treatment with a GFD. This includes control of symptoms, stabilization of diabetes and prevention of complications associated with coeliac disease. The cost per patient diagnosed with coeliac disease from the existing population with Type 1 diabetes would be £860 and for those newly arising £950. [source] Preliminary study of mucosal IgA in the equine small intestine: specific IgA in cases of acute grass sickness and controlsEQUINE VETERINARY JOURNAL, Issue 5 2007F. G. NUNN Summary Reasons for performing study: There is much evidence to suggest that group III Clostridium botulinum (types C and D) are involved in the aetiology of equine grass sickness (EGS). Antibodies have been detected previously in the blood and high levels associated with resistance to disease. Specific mucosal antibodies in the gastrointestinal (GI) tract are likely to be important in protection, and this study was performed to ascertain if such antibodies could be detected and if their levels were related to disease state. Objectives: To develop a method for quantifying IgA antibodies to C. botulinum types C and D in the GI tract of horses and to relate antibody levels to disease status. Methods: Samples of tissue (n = 25: 6 duodenum, 7 jejunum and 12 ileum) were taken from acute grass sickness (AGS) cases and from control horses (n = 12; 4 samples from each site) at post mortem. They were extracted with the detergent saponin in the presence of protease inhibitors and assayed for total IgA, for specific IgA against botulinum neurotoxins types C and D (BoNT/C or BoNT/D), and against surface antigens of a BoNT/C negative strain of C. botulinum type C (SA) and of Clostridium tetani (TetSA), as a control. Specific IgA was expressed as percentage total IgA. Results: Compared to controls, significantly higher levels of specific IgA against BoNT/C were detected in the jejunum (P = 0.04) and ileum (P = 0.02) of AGS cases. Similarly, higher specific levels against BoNT/D were demonstrated in duodenum (P = 0.01) and jejunum (P = 0.02). Significantly higher levels of IgA against SA were demonstrated only in duodenal samples (P = 0.01). Conclusions: Levels of IgA antibody to BoNTs in control horses were at near undetectable levels, suggesting no recent exposure to toxins. In AGS cases, significantly higher levels of specific IgA were detected predominantly in jejunum and ileum. Potential relevance: If specific IgA is protective then any successful vaccine for EGS should induce a mucosal response. [source] Anti-oxidized low-density lipoprotein antibody levels are associated with the development of type 2 diabetes mellitusEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2008L. Garrido-Sánchez Abstract Background, Anti-oxidized low-density lipoprotein (LDL) antibodies are associated with the oxidative capacity of plasma, but whether they protect or promote diabetes is unknown. We undertook a prospective study to determine the predictive capacity of anti-oxidized LDL antibodies for the onset of type 2 diabetes mellitus (T2DM). Materials and methods, We selected 391 non-diabetic women aged 18,65 years. The subjects were classified as being normal (oral glucose test tolerance normal, OGTT-N), or having impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or T2DM according to their baseline glucose levels and after an OGTT. The same subjects were studied six years later. The levels of anti-oxidized LDL antibodies were classified as above or below the 50th percentile. Results, Of the women who were OGTT-N at the start of the study and who had anti-oxidized LDL antibody levels below the 50th percentile, only 65·1% were still OGTT-N after 6 years versus 79·5% of those who had anti-oxidized LDL antibody levels above the 50th percentile (P = 0·015). Women who had IGT or IFG at the start of the study whose anti-oxidized LDL antibody levels were below the 50th percentile had a relative risk of 9·79 (95% confidence interval, 1·40,68·45) of developing diabetes (P < 0·001). Logistic regression analysis showed that the variables predicting the development of a carbohydrate metabolism disorder in the women after 6 years were body mass index (P < 0·001) and the levels of anti-oxidized LDL antibodies (P = 0·042). Conclusions, Levels of anti-oxidized LDL antibodies are independent predictors for the development of T2DM in women. [source] Systemic IFN-, drives kidney nephritis in B6.Sle123 miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Anna-Marie Fairhurst Abstract The impact of IFN-, secretion on disease progression was assessed by comparing phenotypic changes in the lupus-prone B6.Sle1Sle2Sle3 (B6.Sle123) strain and the parental C57BL/6 (B6) congenic partner using an adenovirus (ADV) expression vector containing a recombinant IFN-, gene cassette (IFN-ADV). A comprehensive comparison of cell lineage composition and activation in young B6 and B6.Sle123 mice revealed a variety of cellular alterations in the presence and absence of systemic IFN-,. Most IFN-,-induced phenotypes were similar in B6 and B6.Sle123 mice; however, B6.Sle123 mice uniquely exhibited increased B1 and plasma cells after IFN-, exposure, although both strains had an overall loss of mature B cells in the bone marrow, spleen and periphery. Although most of the cellular effects of IFN-, were identical in both strains, severe glomerulonephritis occurred only in B6.Sle123 mice. Mice injected with IFN-ADV showed an increase in immune complex deposition in the kidney, together with an unexpected decrease in serum anti-nuclear antibody levels. In summary, the predominant impact of systemic IFN-, in this murine model is an exacerbation of mechanisms mediating end organ damage. [source] Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challengeEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2006Nathalie Etchart Abstract We have previously shown that following intranasal exposure to influenza virus, specific plasma cells are generated in the nasal-associated lymphoid tissue (NALT) and maintained for the life of the animal. However, we also showed that following infection with respiratory syncytial virus (RSV), specific plasma cells are generated in the NALT but wane quickly and are not maintained even after challenge, even though RSV-specific serum antibody responses remain robust. Only infection with influenza virus generated sterilising immunity, implying a role for these long-lived plasma cells in protection. We show here that the RSV-specific IgA NALT plasma cell population and lung antibody levels can be substantially boosted, both at acute and memory time points, by intranasal immunisation with inactivated RSV (iRSV) in combination with bacterial outer membrane vesicles (OMV) compared to live RSV alone. Finally, challenge with live RSV showed that immunisation with iRSV and OMV protect against both virus replication in the lung and the eosinophil infiltrate generated by either live RSV or iRSV alone. These data show that immunisation with iRSV and OMV maintains a NALT RSV-specific plasma cell population and generates an efficient protective immune response following RSV infection. See accompanying commentary: http://dx.doi.org/10.1002/eji.200636118 [source] Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseasesEXPERIMENTAL DERMATOLOGY, Issue 2 2007Takashi Matsushita Abstract:, Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma. [source] Evaluation of efficacy in terms of antibody levels and cell-mediated immunity of acellular pertussis vaccines in a murine model of respiratory infectionFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2002Mineo Watanabe Abstract The efficacy of six acellular pertussis vaccines, prepared by various manufacturers in Japan, was investigated in a murine model of respiratory infection (aerosol challenge model) and a murine intracerebral (i.c.) challenge model. There was a good correlation between bacterial clearance from the lungs after aerosol challenge and the potency of vaccines as determined by i.c. challenge. The levels of antibodies against filamentous hemagglutinin were higher after immunizations with all tested vaccines than the levels of antibodies against pertussis toxin and pertactin. Spleen cells from mice immunized with each individual vaccine secreted interferon , (IFN-,) in response to stimulation by pertussis toxin, filamentous hemagglutinin and fimbriae. The production of interleukin-4 in response to each of the antigens tested was detected but was lower than that of IFN-,. However, antibody levels and cell-mediated immune responses were not correlated with the protective effects of the vaccines after aerosol challenge and after i.c. challenge. [source] Salmonella enteritidis temperature-sensitive mutants protect mice against challenge with virulent Salmonella strains of different serotypesFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2000M.Magdalena Gherardi Abstract The protection conferred by temperature-sensitive mutants of Salmonella enteritidis against different wild-type Salmonella serotypes was investigated. Oral immunization with the single temperature-sensitive mutant E/1/3 or with a temperature-sensitive thymine-requiring double mutant (E/1/3T) conferred: (i) significant protection against the homologous wild-type Salmonella strains; (ii) significant cross-protection toward high challenge doses of S. typhimurium. Significant antibody levels against homologous lipopolysaccharide and against homologous and heterologous protein antigens were detected in sera from immunized mice. Moreover, a wide range of protein antigens from different Salmonella O serotypes were recognized by sera from immunized animals. Besides, primed lymphocytes from E/1/3 immunized mice recognized Salmonella antigens from different serotypes. Taken together, these results indicate that temperature-sensitive mutants of S. enteritidis are good candidates for the construction of live vaccines against Salmonella. [source] Systemic Immunization with Unadjuvanted Whole Helicobacter pylori Protects Mice Against Heterologous ChallengeHELICOBACTER, Issue 6 2008Stacey N. Harbour Abstract Background:, Adjuvant-free vaccines have many benefits, including decreased cost and toxicity. We examined the protective effect of systemic vaccination with adjuvant-free formalin-fixed Helicobacter pylori or bacterial lysate and the ability of this vaccine to induce protection against heterologous challenge. Materials and Methods:, Mice were vaccinated subcutaneously with H. pylori 11637 lysate or formalin-fixed bacteria, with or without ISCOMATRIXTM adjuvant, then orally challenged with H. pylori SS1. Serum was taken prior to challenge to examine specific antibody levels induced by the vaccinations, and protection was assessed by colony-forming assay. Results:, Vaccination with H. pylori 11637 lysate or formalin-fixed bacteria delivered systemically induced significantly higher levels of Helicobacter -specific serum IgG than the control, unvaccinated group and orally vaccinated group. After heterologous challenge with H. pylori SS1, all vaccinated groups had significantly lower levels of colonization compared with unvaccinated, control mice, regardless of the addition of adjuvant or route of delivery. Protection induced by systemic vaccination with whole bacterial preparations, without the addition of adjuvants, was only associated with a mild cellular infiltration into the gastric mucosa, with no evidence of atrophy. Conclusions:, Subcutaneous vaccination using unadjuvanted formalin-fixed H. pylori has the potential to be a simple, cost-effective approach to the development of a Helicobacter vaccine. Importantly, this vaccine was able to induce protection against heterologous challenge, a factor that would be crucial in any human Helicobacter vaccine. Further studies are required to determine mechanisms of protection and to improve protective ability. [source] Immune Response to a 26-kDa Protein, Alkyl Hydroperoxide Reductase, in Helicobacter pylori-Infected Mongolian Gerbil ModelHELICOBACTER, Issue 4 2001Jing Yan ABSTRACT Background. The host immune response is thought to play an important role in the outcome of Helico-bacter pylori infection. The successful development of the H. pylori -infected Mongolian gerbil model that mimics human disease has enabled study of the antibody response against H. pylori antigens. Materials and Methods. Serum samples from ulcer and carcinogenesis models of H. pylori -infected gerbils were used to screen for H. pylori antigens that cause a humoral immune response in the infected hosts. H. pylori alkyl hydroperoxide reductase (AhpC) is one such antigen on which we report here. The tsaA gene encoding AhpC was amplified by PCR from H. pylori ATCC 43504 strain, cloned into pMALTM -c2 expression vector and expressed in Escherichia coli. Maltose-binding protein fusion protein (MBP-AhpC) was purified by a MBP affinity column. Using purified recombinant AhpC protein as an antigen, the antibody response and changes of antibody levels against AhpC in the gerbil models were studied by Western blotting and ELISA. Results. Antibody against AhpC was negative in the early stages of infection, and became positive in the gerbils with the emergence of gastric diseases such as chronic active gastritis, gastric ulcer and gastric cancer. The antibody levels (ELISA) increased gradually over time and were higher in gerbils with gastric ulcer than that in gerbils without ulcers. Conclusions. Use of the gerbil model that mimics human H. pylori infection is likely to provide insights into the role of H. pylori -specific antigens possibly related to the subsequent development of gastric diseases. [source] | |||||||||||||||||||||||||||||||||||||||||||