67 research outputs found
The role of HLA-DP mismatches and donor specific HLA-DP antibodies in kidney transplantation : a case series
BACKGROUND:
The impact of HLA-DP mismatches on renal allograft outcome is still poorly understood and is suggested to be less than that of the other HLA loci. The common association of HLA-DP donor-specific antibodies (DSA) with other DSA obviates the evaluation of the actual effect of HLA-DP DSA.
METHODS:
From a large multicenter data collection, we retrospectively evaluated the significance of HLA-DP DSA on transplant outcome and the immunogenicity of HLA-DP eplet mismatches with respect to the induction of HLA-DP DSA. Furthermore, we evaluated the association between the MFI of HLA-DP antibodies detected in Luminex assays and the outcome of flowcytometric/complement-dependent cytotoxicity (CDC) crossmatches.
RESULTS:
In patients with isolated pretransplant HLA-DP antibodies (NâŻ=âŻ13), 6 experienced antibody-mediated rejection (AMR) and 3 patients lost their graft. In HLAMatchmaker analysis of HLA-DP mismatches (NâŻ=âŻ72), HLA-DP DSA developed after cessation of immunosuppression in all cases with 84DEAV (NâŻ=âŻ14), in 86% of cases with 85GPM (NâŻ=âŻ6/7), in 50% of cases with 56E (NâŻ=âŻ6/12) and in 40% of cases with 56A mismatch (NâŻ=âŻ2/5). Correlation analysis between isolated HLA-DP DSA MFI and crossmatches (NâŻ=âŻ90) showed negative crossmatch results with HLA-DP DSA MFI <2000 (NâŻ=âŻ14). Below an MFI of 10,000 CDC crossmatches were also negative (NâŻ=âŻ33). Above these MFI values both positive (NâŻ=âŻ35) and negative (NâŻ=âŻ16) crossmatch results were generated.
CONCLUSIONS:
Isolated HLA-DP DSA are rare, yet constitute a significant risk for AMR. We identified high-risk eplet mismatches that can lead to HLA-DP DSA formation. We therefore recommend HLA-DP typing to perform HLA-DP DSA analysis before transplantation. HLA-DP DSA with high MFI were not always correlated with positive crossmatch results
COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study
Background
To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic.
Methods
This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research networkâthe Paediatric Tuberculosis Network European Trials Group (ptbnet)âthat mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission.
Findings
582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5â12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2â11, range 1â34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72â14·87; p=0·0035), male sex (2·12, 1·06â4·21; p=0·033), pre-existing medical conditions (3·27, 1·67â6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16â21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavirâritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20â1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support.
Interpretation
COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed.
Funding
ptbnet is supported by Deutsche Gesellschaft fĂŒr Internationale Zusammenarbeit
Limitations in chloroplast multiplication in Acetabularia mediterranea
SCOPUS: ar.jinfo:eu-repo/semantics/publishe
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