RESUMO
Organs transplanted across donor-specific HLA antibodies (DSA) are associated with a variety of clinical outcomes, including a high risk of acute kidney graft rejection. Unfortunately, the currently available assays to determine DSA characteristics are insufficient to clearly discriminate between potentially harmless and harmful DSA. To further explore the hazard potential of DSA, their concentration and binding strength to their natural target, using soluble HLA, may be informative. There are currently a number of biophysical technologies available that allow the assessment of antibody binding strength. However, these methods require prior knowledge of antibody concentrations. Our objective within this study was to develop a novel approach that combines the determination of DSA-affinity as well as DSA-concentration for patient sample evaluation within one assay. We initially tested the reproducibility of previously reported affinities of human HLA-specific monoclonal antibodies and assessed the technology-specific precision of the obtained results on multiple platforms, including surface plasmon resonance (SPR), bio-layer interferometry (BLI), Luminex (single antigen beads; SAB), and flow-induced dispersion analysis (FIDA). While the first three (solid-phase) technologies revealed comparable high binding-strengths, suggesting measurement of avidity, the latter (in-solution) approach revealed slightly lower binding-strengths, presumably indicating measurement of affinity. We believe that our newly developed in-solution FIDA-assay is particularly suitable to provide useful clinical information by not just measuring DSA-affinities in patient serum samples but simultaneously delivering a particular DSA-concentration. Here, we investigated DSA from 20 pre-transplant patients, all of whom showed negative CDC-crossmatch results with donor cells and SAB signals ranging between 571 and 14899 mean fluorescence intensity (MFI). DSA-concentrations were found in the range between 11.2 and 1223 nM (median 81.1 nM), and their measured affinities fall between 0.055 and 24.7 nM (median 5.34 nM; 449-fold difference). In 13 of 20 sera (65%), DSA accounted for more than 0.1% of total serum antibodies, and 4/20 sera (20%) revealed a proportion of DSA even higher than 1%. To conclude, this study strengthens the presumption that pre-transplant patient DSA consists of various concentrations and different net affinities. Validation of these results in a larger patient cohort with clinical outcomes will be essential in a further step to assess the clinical relevance of DSA-concentration and DSA-affinity.
Assuntos
Anticorpos Monoclonais , Transplante de Rim , Humanos , Afinidade de Anticorpos , Reprodutibilidade dos Testes , Antígenos HLA , Alelos , Doadores de Tecidos , Teste de Histocompatibilidade/métodos , Rejeição de Enxerto , IsoanticorposRESUMO
La soledad es un factor social que afecta a personas de todas las edades, perjudicando su salud y aumentando la utilización de servicios sociosanitarios. Su abordaje requiere una perspectiva comunitaria integral, ya que es un sentimiento subjetivo con consecuencias complejas en la salud y en el bienestar. En una sociedad envejecida, la soledad se convierte en un problema de salud pública significativo, especialmente entre las personas mayores. Por ello, este estudio se centra en los servicios de ayuda en el hogar (Servicio de Axuda no Fogar, SAF) en Galicia y su papel en la lucha contra la soledad, con el objetivo de comprender este sentimiento entre las personas usuarias del SAF y recopilar sus opiniones para entender cómo abordarla y diseñar estrategias intersectoriales y participativas que permitan ayudar a disminuirla. Los resultados iniciales muestran que más del 50% de los usuarios del SAF se sienten solos. A través de la elaboración de un cuestionario propio y de mediciones utilizando la escala de soledad UCLA, el estudio destaca la importancia de la colaboración comunitaria y la necesidad de difundir los resultados para orientar intervenciones futuras. Se concluye que los SAF tienen un potencial significativo para mejorar el bienestar de los usuarios y abordar la soledad, un factor social determinante de la salud. (AU)
Loneliness is a social factor that impacts individuals of all ages, impairing their health and increasing the use of socio-health services. Tackling this requires a comprehensive community perspective, as it is a subjective feeling with complex consequences for health and well-being. In an aging society, loneliness becomes a significant public health issue, especially among the elderly. Therefore, this study focuses on Home Help Services (SAF) in Galicia and their role in responding to loneliness. The main aim is to understand this feeling among SAF users, gather their opinions on how to tackle this, and devise intersectoral and participatory strategies to reduce loneliness. Initial results reveal that over 50% of SAF users feel lonely. By means of a customized questionnaire and measurements using the UCLA Loneliness Scale, the study underscores the importance of community collaboration and the need to disseminate results to guide future interventions. It is concluded that SAF has significant potential to improve user well-being and tackle loneliness, a decisive social factor on health. (AU)