High-dimensional mass cytometry identified circulating natural killer T-cell subsets associated with protection from cytomegalovirus infection in kidney transplant recipients.

Cytomegalovirus (CMV) infection is associated with poor kidney transplant outcomes. While innate and adaptive immune cells have been implicated in its prevention, an in-depth characterization of the in vivo kinetics of multiple cell subsets and their role in protecting against CMV infection has not been achieved. Here, we performed high-dimensional immune phenotyping by mass cytometry, and functional assays, on 112 serially collected samples from CMV seropositive kidney transplant recipients. Advanced unsupervised deep learning analysis was used to assess immune cell populations that significantly correlated with prevention against CMV infection and anti-viral immune function. Prior to infection, kidney transplant recipients who developed CMV infection showed significantly lower CMV-specific cell-mediated immune (CMI) frequencies than those that did not. A broad diversity of circulating cell subsets within innate and adaptive immune compartments were associated with CMV infection or protective CMV-specific CMI. While percentages of CMV (tetramer-stained)-specific T cells associated with high CMI responses and clinical protection, circulating CD3+CD8midCD56+ NK-T cells overall strongly associated with low CMI and subsequent infection. However, three NK-T cell subsets sharing the CD11b surface marker associated with CMV protection and correlated with strong anti-viral CMI frequencies in vitro. These data were validated in two external independent cohorts of kidney transplant recipients. Thus, we newly describe the kinetics of a novel NK-T cell subset that may have a protective role in post-transplantation CMV infection. Our findings pave the way to more mechanistic studies aimed at understanding the function of these cells in protection against CMV infection.

Performance of Mucorales spp. qPCR in bronchoalveolar lavage fluid for the diagnosis of pulmonary mucormycosis.

To estimate the diagnostic performance of Mucorales polymerase chain reaction (PCR) in Bronchoalveolar lavage fluid (BALF) in routine practice. This was a single-center retrospective study including all consecutive patients >18 years who underwent Mucorales PCR assay in BALF between January 2021 and May 2022. Index testing was prospectively performed using the MycoGENIE Aspergillus spp.-Mucorales spp. PCR. The reference was the diagnosis of pulmonary mucormycosis by the Adjudication Committee. Mucorales PCR in BALF was performed for 938 patients and was positive for 21 of 938 (2.2%). Eleven pulmonary mucormycosis (including one disseminated) were diagnosed. Among them, one (9.1%) was classified as proven mucormycosis, three (27.3%) as probable, and seven (63.6%) as possible according to the EORTC/MSGERC 2019 criteria. The main host factor was hematological malignancy (10 of 11, 90.9%). Mucorales PCR was positive in serum for eight patients (72.7%). Three patients had positive PCR in BALF, but negative in serum. The mean cycle threshold value was significantly lower in mucormycosis than false-positive cases. Sensitivity was 72.7% (95% confidence interval [CI], 43.4-90.3%), and specificity was 98.6% (95% CI, 97.6-99.2%). The positive and negative predictive values were 38.1% (95% CI, 20.8-59.1%) and 99.7% (95% CI, 99.1-99.9%), respectively. Mucorales PCR in BALF showed good diagnostic performance for mucormycosis, particularly in combination with serum PCR. A positive result should be interpreted with caution, given the possibility of carriage in the airway. However, its high negative predictive value and specificity suggest the utility of Mucorales PCR in BALF in the diagnosis of pulmonary mucormycosis.

Improving pre-emptive access to the kidney transplant waiting list between 2017 and 2021: assessment of a regional program in Aquitaine / Amélioration de l'accès préemptif à la liste d'attente de transplantation rénale entre 2017 et 2021 : bilan d'un programme régional en Aquitaine.

Introduction: Pre-emptive access to the kidney transplant (KT) waiting list remains limited in France, with only 3.9% of patients on pre-emptive KT and 5.6% of patients registered at the time of initiation of dialysis. A similar trend was observed in Aquitaine. The aim of this study was to assess the impact of a regional program in terms of access to the waiting list for patients initiating a kidney replacement therapy (KRT). Methods: We included all patients assessed for registration on the list between 2017 and 2020, 2017 being the reference year and 2018 the beginning of the program. Using the CRISTAL and REIN registries, we assessed changes in the number of patients on the list at the time of initiation of dialysis or transplantation. Results: The number of new assessed candidates increased gradually each year from 255 in 2017 to 352 in 2020 (+38%). The number of patients on the list sharply increased in 2018 from 229 in 2017 to 319 in 2018 (+39.3%) and then remained stable. At the initiation of KRT, the proportion of patients registered on the waiting list increased gradually from 7.1% in 2017 to 18.2% in 2020. The proportion of pre-emptive KT remained stable between 2017 and 2021 (around 7%) with a decrease in 2020 (4.6%). Approximately 60% of patients had a contraindication to transplantation throughout the study. Conclusion: This study showed that a regional program aimed at providing better information to healthcare professionals and patients and encouraging rapid assessment of transplant candidates could increase the rate of pre-emptive registration on the KT waiting list for eligible patients over 4 years.

Introduction: L'accès préemptif à la liste d'attente de transplantation rénale (TR) reste limité en France, avec seulement 3,9 % de TR préemptives et 5,6 % de patients inscrits lors de l'initiation de la dialyse. Une tendance similaire était observée en Aquitaine. L'objectif de cette étude était d'évaluer l'impact d'un programme régional en termes d'accès à la liste d'attente chez les patients débutant un traitement de suppléance. Méthodes: Nous avons inclus l'ensemble des patients évalués pour une inscription sur liste entre 2017 et 2020, 2017 étant l'année de référence et 2018 l'année de début du programme régional. Nous avons évalué de façon annuelle, grâce aux registres CRISTAL et REIN, l'évolution du nombre de patients inscrits sur liste lors de l'initiation du traitement de suppléance par dialyse ou transplantation. Résultats: Le nombre de nouveaux candidats évalués a augmenté graduellement chaque année, passant de 255 en 2017 à 352 en 2020 (+ 38 %). Le nombre de patients inscrits sur la liste a fortement augmenté en 2018 passant de 229 en 2017 à 319 en 2018 (+39,3 %), puis est resté stable. À l'initiation du traitement de suppléance, la proportion de patients inscrits a augmenté graduellement passant de 7,1 % en 2017 à 18,2 % en 2020. La proportion de TR préemptive est restée stable entre 2017 et 2021 (environ 7 %) avec une baisse en 2020 (4,6 %). Environ 60 % des patients présentaient une contre-­indication à la transplantation tout au long de cette étude. Conclusion: Cette étude a montré qu'un programme régional visant à mieux informer les professionnels de santé et les patients et favorisant l'évaluation rapide des candidats à la greffe permet d'augmenter en 4 ans le taux d'inscription préemptive sur liste d'attente de TR chez les patients éligibles.