Intravenous immunoglobulin treatment of four patients with juvenile polyarticular arthritis associated with persistent parvovirus B19 infection and antiphospholipid antibodies

Children with rheumatic oligoarthritis and polyarthritis frequently establish persistent parvovirus B19 infections that may be associated with the production of antiphospholipid antibodies (anti-PL IgG). In this study we analysed the influence of high-dose intravenous immunoglobulin (IVIG) therapy on virus load, on the level of anti-PL IgG and its potential capacity to improve the patients' clinical status. Four juvenile patients with long-lasting polyarticular rheumatic diseases and persistent parvovirus B19 infection, associated in three cases with the presence of antibodies against β(2)-glycoprotein I (anti-β(2)GPI IgG), were treated with two cycles of IVIG on five successive days (0.4 g/kg per day). Clinical parameters including scores of disease activity, virus load and anti-PL IgG levels were determined before, during and after treatment. Two patients showed a complete remission that has lasted 15 months. During that period they showed neither clinical nor laboratory signs of inflammation. Viral DNA was not detectable in serum, and a decrease in anti-β(2)GPI IgG was observed. As assessed by the Childhood Health Assessment Questionnaire and the Health-related Quality of Life Questionnaire for Children, both patients were no longer restricted in their activities of daily living and no impact on the health-related quality of life was observed. In one patient the therapy failed: there was no improvement of symptoms and no decrease in virus load or inflammatory parameters. In the fourth patient, clinical and laboratory parameters did not improve despite a decrease in both viral load and anti-PL IgG. Our results show that the use of IVIG to treat parvovirus B19-triggered polyarticular rheumatic disease of childhood might offer an opportunity to improve this disabling condition

Autoantikörpernachweis mittels indirekter Immunfluoreszenz an HEp-2-Zellen

Systemic autoimmune diseases are characterized by the presence of antinuclear autoantibodies (ANAs). Diluted patient sera are typically used to screen for the presence of ANAs by immunofluorescence microscopy with fixed HEp-2 cells. Despite high quality test kits, reports of different laboratories frequently present controversial results. This study presents a recommendation for a unified processing and interpretation of HEp-2 based screening for autoantibodies. We provide suggestions for selection of high quality test kits, optimized processing, and diagnostic procedures. For good laboratory practice, in addition to a relevant clinical diagnosis and an experienced laboratory specialist, the following procedure is highly recommended: initial HEp-2 based screening by indirect immunofluorescence, starting with a 1:80 serum dilution and evaluation in a bright fluorescence microscope, pathological values from a titer of 1:160, internal quality checks, and unified interpretation. We aim to improve diagnostics and care for patients with autoimmune diseases as a central focus of the European Autoimmunity Standardization Initiative (EASI)

Long-term trajectories of SARS-CoV-2 neutralizing antibodies and predictive value of first dose vaccination-induced IgG-antibodies in hemodialysis patients

Purpose!#!The predictive value of antibody titers after the first SARS-CoV-2 vaccination and long-term trajectories of antibody titers in hemodialysis patients are unknown.!##!Methods!#!SARS-CoV-2 IgG antibodies and their neutralizing effect six weeks after the first and second vaccination were analysed in 30 hemodialysis patients. IgG titers served to classify participants as responders or non-responders and to calculate sensitivity, specificity, and accuracy. Associations between potential risk factors and post-vaccine non-response were analysed by Mann-Whitney-U test and Chi-Squared test. Long-term follow-up analysis (ANOVA) on the evolution of neutralizing IgG-titers was performed in 24 participants 94 and 135 days after the second immunization.!##!Results!#!IgG antibodies ≥ 1 AU/L (mean 9 ± 20 AU/L) after the first dose were found in 20 patients (66.7%). After the second dose only two participants (6.7%) remained sero-negative and 16.6% showed neutralizing levels below 30%, whereas 25 patients showed IgG antibodies with the high neutralizing activity of 86 ± 18%. Positive IgG antibodies 6 weeks after the first vaccination predicted vaccination effectiveness after two cycles with a specificity of 100%, sensitivity of 76%, and accuracy of 87%. Even low-dose immunosuppressive therapy increased the relative risk for non-response after the first and second dose 1.9 (95% CI 0.8-4.6) and 4.9 (95% CI 1.0-23.8) times, respectively. Over a period of about 4.5 months IgG titers slowly declined by 51% from baseline or by 0.45 AU/mL per day, respectively.!##!Conclusion!#!Two cycles of SARS-CoV-2 vaccination-induced high seroconversion rates comparable to the general population. Immunosuppressive medication is a major risk factor for vaccination non-response. Mounted IgG antibodies showed a high neutralizing capacity as evidence of protective effectiveness. IgG antibodies after the first dose may serve to predict later vaccination outcome. Patients on dialysis display a more rapid decline in antibody titers on long-term follow-up compared to healthy controls

A case of Waldenstroem's disease with a monoclonal IgM antiphospholipid antibody

The antiphospholipid syndrome (APS) was described in 1983 as a clinical entity characterized by venous and arterial thrombosis, thrombocytopenia, and recurrent fetal loss. The serological markers of APS are antiphospholipid antibodies (APLA) directed mainly against anionic phospholipids, usually cardiolipin but also phosphatidylserine. Some APLA exhibit lupus anticoagulant activity. Monoclonal gammopathy sometimes occurs with the presence of autoantibodies. In this paper, we describe a patient with the diagnosis of immunocytoma with an IgM, kappa paraprotein with apparent specificity against anionic phospholipids, and lupus anticoagulant activity, but no clinical signs of APS. We describe in this patient the presence of a high titer of monoclonal APLA, which does apparently not induce the clinical symptoms of APS. This might be indicative for the presence of pathogenic and nonpathogenic antiphospholipid antibodies

Effect of Third and Fourth mRNA-Based Booster Vaccinations on SARS-CoV-2 Neutralizing Antibody Titer Formation, Risk Factors for Non-Response, and Outcome after SARS-CoV-2 Omicron Breakthrough Infections in Patients on Chronic Hemodialysis: A Prospective Multicenter Cohort Study

The aim of this study is to determine the effect of repeated vaccinations on neutralizing SARS-CoV-2 IgG antibody titers, evaluate risk factors for immunological non-response, and to report breakthrough infections in chronic hemodialysis patients. Methods: A prospective, multi-center cohort study in 163 chronic hemodialysis patients was conducted. Antibody titers were measured three months after second, third, and fourth (10 pts) booster vaccinations. SARS-CoV-2 neutralizing antibody titers in BAU/mL and % inhibition were divided into three categories (433 and 66%). Somers’s test, paired t-test, and univariable and multivariable logistic regression analysis were applied to evaluate differences in antibody levels and search for risk factors for vaccination failure defined as neutralizing titers n = 10) and breakthrough infections (n = 20). Results: Third dose boosters resulted in higher proportions of patients with neutralizing antibody levels >66% as compared to after the second dose (64.7% after second dose vs. 88.9% after third dose, p = 0.003), as well as in a respective increase in neutralizing titer levels in % from 68 ± 33% to 89 ± 24 (p p ≤ 0.001). Age (p = 0.004, OR 1.066, 95% CI 1.020–1.114) and presence of immunosuppressive medications (p = 0.002, OR 8.267, 95% CI 2.206–30.975) were identified as major risk factors for vaccination failure. Repeated booster vaccinations ≥4 times were effective in 8 out of 10 former low-responders (80%) without any side effects or safety concerns. Breakthrough infections showed a clinically mild course but were associated with prolonged viral shedding on PCR-testing ranging 7–29 (mean 13) days. Conclusions: Third and fourth mRNA-based booster vaccinations resulted in higher and longer lasting SARS-CoV-2 antibody levels as compared to after two dosages. The presence of immunosuppressive medication and repeat vaccinations are major potentially modifiable measures to increase antibody levels in non-or low-responders. Breakthrough infections with SARS-CoV-2 Omicron were associated with prolonged viral shedding but clinically mild disease courses

Interaction of TLR2 and TLR4 ligands with the N-terminal domain of Gp96 amplifies : innate and adaptive immune responses

Activation of dendritic cells by ligands for Toll-like receptors (TLR) is a crucial event in the initiation of innate and adaptive immune responses. Several classes of TLR ligands have been identified that interact with distinct members of the TLR-family. TLR4 ligands include lipopolysaccharide derived from different Gram-negative bacteria and viral proteins. Recent reports have demonstrated the TLR-mediated activation of dendritic cells by heat shock proteins (HSPs). However, doubts were raised as to what extent this effect was due to lipopolysaccharide contaminations of the HSP preparations. We re-examined this phenomenon using Gp96 or its N-terminal domain, nominally endotoxin-free ( or =50 microg/ml) but not at lower concentrations. However, preincubation of low amounts of Gp96 with TLR2 and TLR4 ligands at concentrations unable to activate dendritic cells by themselves results in the production of high levels of proinflammatory cytokines, up-regulation of activation markers, and amplification of T cell activation. Our results provide significant new insights into the mechanism of HSP-mediated dendritic cell activation and present a new function of HSPs in the amplification of dendritic cell activation by bacterial products and induction of adaptive immune responses

Increased Severe Adverse Outcomes and Decreased Emergency Room Visits for Pyelonephritis: First Report of Collateral Damage during COVID-19 Pandemic in Urology

Purpose: The coronavirus disease 2019 (COVID-19) pandemic is disrupting urology health-care worldwide. Reduced emergency room visits resulting in adverse outcomes have most recently been reported in pediatrics and cardiology. We aimed to compare patients with emergency room visits for pyelonephritis in 2019 (pre-COVID-19 era) and within the first wave of pandemic in 2020 (COVID-19 era) with regard to the number of visits and severe adverse disease outcomes. Methods: We performed a retrospective multicentre study comparing characteristics and outcomes of patients with pyelonephritis, excluding patients with hydronephrosis due to stone disease, in 10 urology departments in Germany during a 1-month time frame in March and April in each 2019 and 2020. Results: The number of emergency room visits for pyelonephritis in the COVID-19 era was lower (44 patients, 37.0%) than in the pre-COVID-19 era (76 patients, 63.0%), reduction rate: 42.1% (p = 0.003). Severe adverse disease outcome was more frequent in the COVID-19 era (9/44 patients, 20.5%) than in the pre-COVID-19 era (5/76 patients, 6.6%, p = 0.046). In detail, 7 versus 3 patients needed monitoring (15.9 vs. 3.9%), 2 versus no patients needed intensive-care treatment (4.5 vs. 0%), 2 versus no patients needed drain placement (4.5 vs. 0%), 2 versus no patients had a nephrectomy (4.5 vs. 0%), and 2 versus 1 patient died (4.5 vs. 1.3%). Conclusion: This report of collateral damage during CO-VID-19 showed that emergency room visits were decreased, and severe adverse disease outcomes were increased for patients with pyelonephritis in the COVID-19 era. Health authorities should set up information campaign programs actively encouraging patients to utilize emergency room services in case of severe symptoms specifically during the actual second wave of pandemic. (c) 2021 S. Karger AG, Base

Racial disparity in quality of care and overall survival among black vs. white patients with muscle-invasive bladder cancer treated with radical cystectomy: A national cancer database analysis.

OBJECTIVES: To examine the impact of race on quality of care and overall survival (OS) among patients with muscle invasive bladder cancer (MIBC) treated with radical cystectomy (RC) in the U.S. MATERIALS & METHODS: Our cohort consisted of 12,652 patients receiving RC for MIBC within the National Cancer Database from 2004 to 2012. Patients were stratified by race (Black non-Hispanic vs. White non-Hispanic) and imbalances in patient characteristics mitigated using propensity score weighting. Logistic and Cox regressions examined the impact of race on quality of care metrics (receipt of pelvic lymph node dissection (PLND), lymph node count, hospital volume, length of stay, delay of treatment) and on OS. The difference in OS was expressed as Delta, and stratified by facility-type, hospital volume, and region. RESULTS: Blacks were less likely to receive PLND (odds ratio [OR] 0.70, 95% confidence interval [CI]: 0.55-0.91), or to have a greater number of lymph nodes removed (OR 0.76, 95%CI: 0.64-0.90). They exhibited greater length of stay (OR 1.34, 95%CI: 1.13-1.59), and delay of RC among recipients of neoadjuvant chemotherapy (OR 2.59, 95%CI: 1.77-3.85) (all P ≤ 0.001). Notably, utilization of neoadjuvant chemotherapy in advanced disease stages was more common in blacks (OR 2.82, 95%CI: 1.93-4.13, P \u3c 0.001). Additionally, Black race was associated with inferior OS (Hazard ratio 0.87, 95%CI: 0.79-0.97, P \u3c 0.014). Disparities in OS varied based on facility type and geographical region, but not hospital volume. Specifically, Blacks had worse OS when treated in a community cancer program (Delta 0.42, 95%CI: 0.28-0.57,P \u3c 0.001), or within New England/Middle Atlantic region (Delta 0.16, 95% CI: 0.07-0.24,P \u3c 0.001). CONCLUSION: Black race is an independent predictor of inferior quality of care and OS in patients undergoing RC for MIBC. Survival disparities vary based on geographical region and facility type. Notably, the OS disparity appears to have narrowed in comparison to previous studies