Search

HLA-A*03:57 has two amino acid exchanges in exon 2 at adjacent positions of the peptide-binding groove. [ABSTRACT FROM AUTHOR]

Background and Objectives: Early neuroprognostication in children with reduced consciousness after cardiac arrest (CA) is a major clinical challenge. EEG is frequently used for neuroprognostication in adults, but has not been sufficiently validated for this indication in children. Using machine learning techniques, we studied the predictive value of quantitative EEG (qEEG) features for survival 12 months after CA, based on EEG recordings obtained 24 hours after CA in children. The results were confirmed through visual analysis of EEG background patterns., Methods: This is a retrospective single-center study including children (0-17 years) with CA, who were subsequently admitted to the pediatric intensive care unit (PICU) of a tertiary care hospital between 2012 and 2021 after return of circulation (ROC) and were monitored using EEG at 24 hours after ROC. Signal features were extracted from a 30-minute EEG segment 24 hours after CA and used to train a random forest model. The background pattern from the same EEG fragment was visually classified. The primary outcome was survival or death 12 months after CA. Analysis of the prognostic accuracy of the model included calculation of receiver-operating characteristic and predictive values. Feature contribution to the model was analyzed using Shapley values., Results: Eighty-six children were included (in-hospital CA 27%, out-of-hospital CA 73%). The median age at CA was 2.6 years; 53 (62%) were male. Mortality at 12 months was 56%; main causes of death on the PICU were withdrawal of life-sustaining therapies because of poor neurologic prognosis (52%) and brain death (31%). The random forest model was able to predict death at 12 months with an accuracy of 0.77 and positive predictive value of 1.0. Continuity and amplitude of the EEG signal were the signal parameters most contributing to the model classification. Visual analysis showed that no patients with a background pattern other than continuous with amplitudes exceeding 20 μV were alive after 12 months., Discussion: Both qEEG and visual EEG background classification for registrations obtained 24 hours after ROC form a strong predictor of nonsurvival 12 months after CA in children.

Background: Preformed donor-specific HLA antibodies (DSA) are a well-known risk factor in kidney transplantation. There is still considerable debate, however, about the optimal risk stratification among patients with preformed DSA. Additionally, data on the prognostic value of different crossmatch assays in DSA-positive patients are scarce., Methods: DSA-positive living kidney transplant recipients were selected from a multicenter study examining 4233 consecutive renal transplants. An additional 7 patients from 2 further centers were included. Flow cytometric crossmatches (FXM), Luminex-based crossmatches, and virtual crossmatches based on C1q- and C3d-binding antibodies (C1qXM and C3dXM) were performed retrospectively using pretransplant sera and lymphocytes isolated from fresh samples. These samples were obtained from 44 donor and recipient pairs from 12 centers. Clinical outcome data and the control group without DSA were compiled from the previous study and were supplemented by data on 10-y death-censored graft survival (10yGS)., Results: Between 19% (C3dXM) and 46% (FXM) of crossmatches were positive. Crossmatch-positive patients showed high incidences of antibody-mediated rejection (AMR) within 6 mo (up to 60% in B-cell FXM+ patients). The incidence of AMR in crossmatch-negative patients ranged between 5% (FXM-) and 13% (C1qXM-). 10yGS was significantly impaired in patients with positive T-cell FXM and total FXM compared with both patients without DSA and those with DSA with negative FXM., Conclusions: Especially FXM are useful for risk stratification, as the outcome of DSA-positive, FXM-negative patients is similar to that of DSA-negative patients, whereas FXM-positive patients have both more AMR and decreased 10yGS. Because of their lower sensitivity, the significance of Luminex-based crossmatches, C1qXM, and C3dXM would have to be examined in patients with stronger DSA., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10 -6 ), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10 -8 ), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10 -6 ). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Pretransplant allosensitization to human leukocyte antigens (HLA) increases the recipient's waiting list time and mortality in lung transplantation. Rather than waiting for crossmatch-negative donors, since 2013, recipients with preformed donor-specific antiHLA antibodies (pfDSA) have been managed with repeated IgA- and IgM-enriched intravenous immunoglobulin (IgGAM) infusions, usually in combination with plasmapheresis before IgGAM and a single dose of antiCD20 antibody. This retrospective study presents our 9-year experience with patients transplanted with pfDSA. Records of patients transplanted between February 2013 and May 2022 were reviewed. Outcomes were compared between patients with pfDSA and those without any de novo donor-specific antiHLA antibodies. The median follow-up time was 50 months. Of the 1,043 patients who had undergone lung transplantation, 758 (72.7%) did not develop any early donor-specific antiHLA antibodies, and 62 (5.9%) patients exhibited pfDSA. Among the 52 (84%) patients who completed treatment, pfDSA was cleared in 38 (73%). In pfDSA vs control patients and at 8-year follow-up, respectively, graft survival (%) was 75 vs 65 (P = .493) and freedom from chronic lung allograft dysfunction (%) was 63 vs 65 (P = .525). In lung transplantation, crossing the preformed HLA-antibody barrier is safe using a treatment protocol based on IgGAM. Patients with pfDSA have a good 8-year graft survival rate and freedom from chronic lung allograft dysfunction, similar to control patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fabio Ius reports financial support was provided by Biotest AG. Christine Falk reports financial support was provided by Biotest AG. Christine Falk reports financial support was provided by SFB 738 B3. Fabio Ius reports a relationship with Biotest AG that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Gregor Warnecke and Wiebke Sommer declare congress fees, study grants and honorary for lectures paid by Biotest AG., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Abnormalities at any stage of trophoblast development may result in pregnancy-related complications. Many of these adverse outcomes are discovered later in pregnancy, but the underlying pathomechanisms are constituted during the first trimester. Acquiring developmentally relevant material to elucidate the disease mechanisms is difficult. Human pluripotent stem cell (hPSC) technology can provide a renewable source of relevant cells. BMP4, A83-01, and PD173074 (BAP) treatment drives trophoblast commitment of hPSCs toward syncytiotrophoblast (STB), but lacks extravillous trophoblast (EVT) cells. EVTs mediate key functions during placentation, remodeling of uterine spiral arteries, and maintenance of immunological tolerance. We optimized the protocol for a more efficient generation of HLA-G pos EVT-like trophoblasts from primed hiPSCs. Increasing the concentrations of A83-01 and PD173074, while decreasing bulk cell density resulted in an increase in HLA-G of up to 71%. Gene expression profiling supports the advancements of our treatment regarding the generation of trophoblast cells. The reported differentiation protocol will allow for an on-demand access to human trophoblast cells enriched for HLA-G pos EVT-like cells, allowing for the elucidation of placenta-related disorders and investigating the immunological tolerance toward the fetus, overcoming the difficulties in obtaining primary EVTs without the need for a complex differentiation pathway via naïve pluripotent or trophoblast stem cells.

HLA-C*15:255 differs from HLA-C*15:02:01 by five nucleotide substitutions located in exons 4 and 5., (© 2023 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)

HLA-DPB1*1447:01 differs from HLA-DPB1*04:01:01 by a single nucleotide in exon 2 from A to C at position 134., (© 2023 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)

HLA-B*35:574N contains a single nucleotide substitution at nucleotide position 2 (ATG to ACG)., (© 2023 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)

HLA-C*07:1044N differs from HLA-C*07:01:01:01 by a single nucleotide deletion in exon 3, codon 124, nt. 442., (© 2023 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)

Subcutaneous emphysema, pneumothorax and pneumomediastinum are well-known complications of invasive ventilation in patients with acute hypoxemic respiratory failure. We determined the incidences of air leaks that were visible on available chest images in a cohort of critically ill patients with acute hypoxemic respiratory failure due to coronavirus disease of 2019 (COVID-19) in a single-center cohort in the Netherlands. A total of 712 chest images from 154 patients were re-evaluated by a multidisciplinary team of independent assessors; there was a median of three (2-5) chest radiographs and a median of one (1-2) chest CT scans per patient. The incidences of subcutaneous emphysema, pneumothoraxes and pneumomediastinum present in 13 patients (8.4%) were 4.5%, 4.5%, and 3.9%. The median first day of the presence of an air leak was 18 (2-21) days after arrival in the ICU and 18 (9-22)days after the start of invasive ventilation. We conclude that the incidence of air leaks was high in this cohort of COVID-19 patients, but it was fairly comparable with what was previously reported in patients with acute hypoxemic respiratory failure in the pre-COVID-19 era.

HLA-A*03:420 differs from HLA-A*03:01:01:01 by a single nucleotide in exon 1, codon -22., (© 2022 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)