Transplantation, Год журнала: 2025, Номер unknown
Опубликована: Март 13, 2025
Host-Microbe Multiomic Profiling Identifies Distinct COVID-19 Immune Dysregulation in Solid Organ Transplant Recipients Pickering H, Schaenman J, Phan HV, et al. Nat Commun. 2025;16:586 Despite being immunocompromised because of chronic immunosuppression, solid organ transplant (SOT) recipients do not experience worse mortality compared with nontransplant recipients.1 This observation suggests that their immune responses to COVID-19, despite baseline are complex, potentially influencing both disease susceptibility and protective mechanisms. However, the characterization these remains limited. In study, al2 conducted a case-control analysis 86 vaccine-naive SOT 172 age- sex-matched controls hospitalized for at 20 sites across United States. Plasma, serum, peripheral blood mononuclear cells, nasal swabs were serially collected several time points from index hospitalization. Using established outcome trajectory groups 1–5,3 authors examined correlations between immunological parameters. found have significantly higher SARS-CoV-2 viral loads presentation, along impaired clearance non-SOT controls. Mass cytometry cells revealed plasmablasts transitional B notably less abundant as was anti-SARS-CoV-2 spike IgG level. Interestingly, proximity extension assays serum showed cytokines chemokines (including C-X3-C motif chemokine ligand 1, interleukin-15 receptor subunit alpha, KIT ligand), whereas others lower interferon gamma, oncostatin M, tumor necrosis factor superfamily member 14, C-C 4). Consistent findings, gene set enrichment PBMC transcriptomics demonstrated increased expression innate immunity pathways related complement activation, type I signaling, interleukin (IL)-1 signaling recipients; importantly, remained upregulated over but decreased Similarly, longitudinal swab genes IL-1 (among other pathways) upper respiratory tract on hospital admission, mirroring findings blood. Notably, most observations independent load, suggesting virus-independent factors may drive enhanced systemic proinflammatory seen recipients. Additionally, did differ taking tacrolimus those receiving mycophenolate. The also evaluated correlates severity individuals. recipients, associated reduced CD8+ central memory T CD11c+CXCR5– CD56hiCD16lo natural killer well T-cell CD28 phosphorylation CD3 ζ chains. contrast, features observed Disease linked toll-like airways. there only weak association study is first use multiomics approach examine broad range parameters COVID-19. It has key clinical implications. First, relatively correlation implies immunomodulatory therapies, such IL-6 inhibitors or janus kinase inhibitors, confer same benefit general population. Second, lack an versus mycophenolate common practice discontinuing hospitalization be supported by existing data. Overall, highlight biomarkers predicting could population, underscoring need mechanistic, data-driven interventions improve outcomes this vulnerable group. Compassionate Access Virus-specific Cells Adoptive Immunotherapy Over 15 y Neller MA, Ambalathingal GR, Hamad N, 2024;15:10339. Viral infection leading cause posttransplant morbidity, causing specific syndromes allograft dysfunction.1 infections often targeted therapeutic options than reducing immunosuppression resistant antiviral therapy. cellular therapy introduced early 1990s potential treatment cytomegalovirus (CMV) following allogeneic hematopoietic stem cell transplantation,2 it since been expanded target pathogens, including Epstein-Barr virus (EBV), BK virus, John Cunningham adenovirus. recent publication Nature Communications, al3 described 15-y comprehensive case series patients who treated virus-specific cells. isolated healthy donors stimulated HLA class I– II–restricted peptide epitopes, followed 14–17 d culture presence interleukin-2. By using epitopes EBV, CMV, john cunningham adenovirus, multiple specificities generated. then screened alloreactivity co-culture single-allele reporter lines, ensuring no alloantigens. A proprietary matching algorithm used ensure least 1–2 shared alleles, allowing recognition HLA-restricted presented recipient. way, bank created made available "off-the-shelf" compassionate immunosuppressed infections. Seventy-eight therapy: 50 17 remaining 11 had varied underlying diseases, cancers, autoimmune disease, primary immunodeficiency. Results similar groups, 35 (70%) 14 (82%) showing improvement, respectively. complete remission achieved 5 (10%) 1 (6%), highlighting difficulties establishing persistent latency chronically patient Importantly, tolerated safe, reported serious adverse events, cases graft-versus-host rejection. These results consistent reports multivirus-specific therapies CMV EBV reactivation posttransplantation.4 eligible trials current advanced refractory high-quality control data comparison. design limitations prevented randomization, noted greatest efficacy appeared earlier course. Establishing appropriate place adoptive within regimens, therefore, challenging. One consideration remain susceptible immunosuppressive medications vivo. novel strategy engineer resistance CRISPR-Cas9 might enhance efficacy.5 Ultimately, even where alternative proves standard treatment, appear safe moderately effective inducing response. Future will essential clarify optimal scenarios investigate differences response various viruses conditions.
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